Clinical trial on the effect of tranexamic acid on bleeding and fibrinolysis in primary hip and knee replacement | Revista Española de Anestesiología y Reanimación (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Total hip arthroplasty &#40;THA&#41; and total knee arthroplasty &#40;TKA&#41; are surgeries that often require transfusions&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Different studies have verified the effectiveness of tranexamic acid &#40;TXA&#41; in reducing bleeding and transfusion requirements in patients undergoing these surgeries&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; some aspects of the mechanism of action of TXA remain obscure&#46; According to some authors&#44; TXA has a local antifibrinolytic effect in the surgical field due to accumulation in the extracellular space&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> However&#44; it has no systemic action&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> and therefore will not prevent clot formation in other territories&#46; Others speculate that tourniquet-induced ischaemia during TKA generates more local fibrinolysis&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> and therefore an antifibrinolytic would be more effective&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the meta-analyses published to date&#44; TXA has not been associated with an increased risk of deep vein thrombosis &#40;DVT&#41; or pulmonary embolism &#40;PE&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#8211;4&#44;8</span></a> However&#44; no studies focussing primarily on the detection of thromboembolic complications have yet been published&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We hypothesised that surgery performed with tourniquet-induced ischaemia can increase fibrinolysis&#46; Under this premise&#44; antifibrinolytic treatment should be more effective and would reduce the need for transfusion&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The primary objective was to compare the effect of a specific dose of TXA on transfusion requirements and bleeding in each type of intervention&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The secondary objective was to compare the effect of TXA on fibrinolysis in the 2 procedures&#46; We hoped to determine whether fibrinolysis is more easily activated in surgeries involving tourniquet-induced ischaemia&#44; and how these procedures are affected by the administrations of an antifibrinolytic agent&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally&#44; we recorded the appearance of thromboembolic complications in all patients&#44; identified both proactively and prospectively&#44; even before the clinical manifestation of thrombosis&#44; in all patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study was approved by the Spanish Agency of Medicines and Medical Devices &#40;EudraCT2007-000193-22&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Patients scheduled for TKA and THA were considered eligible for the study&#46; Exclusion criteria were&#58; allergy to TXA or radiological contrast media&#44; history of thromboembolism &#40;to avoid exposing patients with previously undetected thrombophilia to TXA&#41;&#44; coagulopathy&#44; and kidney failure with glomerular filtration &#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#46; Cerebrovascular disease&#44; coronary ischaemia&#44; treatment with 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day aspirin or with anticoagulants after suspension of aspirin and normalisation of INR levels were not considered criteria for exclusion&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">After signing the informed consent form&#44; patients were assigned a sequential identification number&#46; Using randomisation software&#44; each number was randomised to receive TXA or placebo&#44; and placed in a sealed envelope&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">An independent anaesthetist prepared 2 vials containing 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg TXA &#40;Amchafibrin&#44; Agenzia-Ecopharma Laboratories&#41; or placebo &#40;saline solution&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Following the double blind protocol&#44; the researcher administered the medication in 2 infusions&#58; 30<span class="elsevierStyleHsp" style=""></span>min before and 3<span class="elsevierStyleHsp" style=""></span>h after the incision&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The anaesthesia protocol prioritised the use of spinal anaesthesia&#44; but general anaesthesia was also permitted&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In the case of TKA&#44; the tourniquet was inflated to 350<span class="elsevierStyleHsp" style=""></span>mmHg during surgery&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The prostheses used were&#58; U2 &#40;United Orthopedic Corporation&#41; cemented prosthesis in TKA and Shy-Karey &#40;Surgival&#41; in THA&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Patients received 3500<span class="elsevierStyleHsp" style=""></span>IU&#47;day bemiparin&#44; starting 6<span class="elsevierStyleHsp" style=""></span>h after the end of surgery&#44; and continuing until the third or fourth postoperative week&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">If haemoglobin &#40;Hb&#41; levels fell to below 8<span class="elsevierStyleHsp" style=""></span>g&#47;dL or the patient showed signs of anaemia&#44; the protocol permitted the transfusion of red blood cells&#46; A re-infusion drainage tube &#40;ABT Bellovac&#44; Astra Tech&#44; SA L&#8217;Hospitalet de Llobregat&#41; was used in all patients&#59; if more than 400<span class="elsevierStyleHsp" style=""></span>mL blood was collected&#44; it was re-infused 6<span class="elsevierStyleHsp" style=""></span>h after surgery&#44; once samples had been collected and tested for fibrinolysis&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">We tested blood samples before anaesthesia induction&#44; at the end of surgery&#44; and at 6 and 96 postoperative hours&#46; Other blood tests might have been required before the fourth postoperative day to decide whether transfusion was needed&#46; According to some studies&#44; Hb values are usually lowest on the fourth postoperative day&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Blood was drawn in tubes with 3&#46;2&#37; sodium citrate tubes &#40;for clotting&#47;fibrinolysis&#41;&#44; 15&#37; EDTA tubes &#40;for blood count&#41; or lithium heparin tubes &#40;for biochemistry&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The following tests were performed&#58; Hb concentration&#44; haematocrit&#44; platelet count&#44; prothrombin time&#44; activated partial thromboplastin time ratio&#44; and Clauss fibrinogen &#40;all according to standard methods used in our hospital&#41;&#46; Samples that were subsequently sent to an external laboratory for analysis of both fibrinolysis and clotting were processed for long-term storage as follows&#58; the blood was centrifuged at 2000<span class="elsevierStyleHsp" style=""></span>G &#40;20<span class="elsevierStyleHsp" style=""></span>min&#41; and the extracted plasma was frozen at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The following ELISA tests were performed&#58; <span class="elsevierStyleSmallCaps">d</span>-dimer &#40;Asserachrom D-Dimer&#44; Roche&#41;&#44; plasmin-antiplasmin complexes &#40;PAP&#41; &#40;Technozym PAP complex&#44; Technoclone ELISA kit&#41;&#44; thrombin-antithrombin complexes &#40;TAT&#41; &#40;Enzygnost TAT micro ELISA system&#44; Siemens&#41;&#44; and type 1 plasminogen activator inhibitor &#40;PAI-1&#41; &#40;Zymutest PAI-1 Activity by Hyphen&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Blood losses were estimated on the basis of the blood collected in the reinfusion drains&#44; subtracting the volume of washing liquid and weighing the filters&#46; In the case of knee surgery&#44; which involved tourniquet-induced ischaemia&#44; blood loss was negligible&#44; and therefore recorded as 0&#46; Blood from the reinfusion drain was evaluated at 96<span class="elsevierStyleHsp" style=""></span>h&#46; Finally&#44; total blood loss was calculated as the difference between preoperative and 96<span class="elsevierStyleHsp" style=""></span>h postoperative haematocrit levels&#44; using Brecher&#39;s algorithm&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">At 96 postoperative hours&#44; all patients were examined for thromboembolic complications&#44; as follows&#58;</p><p id="par0120" class="elsevierStylePara elsevierViewall">&#40;1&#41; Ultrasound&#44; using a 5-MHz linear transducer&#44; scanning from the groin towards the foot&#44; from the common femoral vein to the deep venous system &#40;superficial femoral artery&#44; popliteal artery&#44; posterior tibial artery and peroneal branches&#41;&#46; The vessels were tested for compressibility&#44; indicating the absence of DVT&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">&#40;2&#41; Computed tomography angiography &#40;CT-Somaton-Sensation 16&#8482;&#44; Siemens&#41;&#46; After injection of iodinated contrast&#44; 0&#46;75<span class="elsevierStyleHsp" style=""></span>mm collimated slices were taken at the level of the lungs&#44; with a reconstructed thickness of 1<span class="elsevierStyleHsp" style=""></span>mm and 0&#46;4<span class="elsevierStyleHsp" style=""></span>mm overlap&#44; to detect the presence of PE&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In order to minimise the risk of bias&#44; a single radiologist performed all the doppler ultrasound scans&#44; and another radiologist performed the CT scans&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Patients underwent daily physical examination in the postoperative period to detect signs of thrombosis&#44; indicating Doppler or lung CT in the case of suspicion&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Three months after hospital discharge&#44; patients were contacted by phone and asked to report any complications&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Finally&#44; 1 year after surgery&#44; follow-up was completed by reviewing each patient&#39;s hospital records and primary care clinical history&#46; The presence of late thromboembolic complications was also verified&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0150" class="elsevierStylePara elsevierViewall">The main endpoint was the percentage of patients requiring transfusion&#46; Secondary variables were postoperative bleeding and the incidence of DVT and PE&#46; We also compared clotting and fibrinolysis parameters&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Sample size was calculated using M&#46;A&#46;S software &#40;Glaxo-Welcome&#41;&#44; based solely on the main variable and one of the fibrinolysis parameters&#46; This is because attempting to find differences in all the secondary variables &#40;particularly complications thromboembolic&#41; would have required a sample size beyond the resources available for this study&#46; The endpoint in the control group was the average transfusion rate in our hospital &#40;18&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> A percentage change of 75&#37; in the transfusion rate was considered significant&#46; With a type 1 error of 0&#46;05 &#40;<span class="elsevierStyleItalic">z</span>&#91;1-alpha&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;96&#41; and a type 2 error of 0&#46;1 &#40;<span class="elsevierStyleItalic">z</span>&#91;1-beta&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;28&#41;&#44; a unilateral test and 5&#37; losses&#44; the sample size calculated was 42 subjects&#46; In the case of fibrinolysis parameters&#44; a minimum D dimer difference of 2000<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L was considered significant<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#59; assuming the same alpha risk of 0&#46;05 and a beta risk of less than 0&#46;2 in a 2-tailed test&#44; 7 subjects were needed per group &#40;total 28&#41;&#44; assuming an SD of 1000<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#46; The sample size based on blood transfusion&#44; being greater&#44; was used for the study&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The need for transfusion&#44; biological&#44; analytical and radiological parameters&#44; and the incidence of adverse effects were compared using a chi-square test&#44; Yates correction&#44; or Fisher&#39;s test for categorical variables&#46; Analysis of variance was used to compare quantitative variables&#46; Non-parametric tests &#40;chi-square and Kruskal&#8211;Wallis&#41; were used for variables with non-normal distribution &#40;Levene-statistic&#41;&#46; Statistical significance was established at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0165" class="elsevierStylePara elsevierViewall">We aimed to recruit 63 patients&#44; 33 scheduled for TKA and 30 for THA&#46; Eleven patients scheduled for TKA and 8 for THA refused to participate&#46; Finally&#44; 22 patients scheduled for TKA were randomised to receive TXA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; or placebo &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and 22 scheduled for THA were randomised to receive TXA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; or placebo &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; All patients in both groups completed the study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">Seven patients &#40;5 in the control group and 2 in the TXA group&#41; received elemental iron&#44; and 1 &#40;in the control group&#41; also received recombinant human erythropoietin to reduce the risk of transfusion&#46; All 4 groups were comparable in terms of age&#44; sex&#44; body mass index&#44; ASA score and other preoperative and postoperative study parameters &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">Patients with thromboembolic risk were included in the study&#46; The control group included 2 patients with a history of stroke&#44; 1 with coronary disease&#44; another with atrial fibrillation&#44; and another with peripheral artery disease&#46; In the TXA group&#44; 2 patients had hypertensive cardiomyopathy&#44; 1 presented atrial fibrillation&#44; and another aortic stenosis&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarises the efficacy and safety outcomes&#46; Blood loss&#44; based on the volume of postoperative drainage&#44; was lower in patient receiving TXA &#40;mean &#91;SD&#93;&#41; 190 &#40;167&#41; mL in THA and 392 &#40;376&#41; mL in TKA vs&#46; 449 &#40;355&#41; mL in THA and 518 &#40;339&#41; mL in TKA treated with placebo&#46; There were no differences in estimated hidden blood losses &#40;estimated total bleeding less drain volume&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Reduction in Hb levels were more severe and occurred earlier in the placebo group &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Hb reduction was less severe in patients receiving TXA&#58; in the TXA group&#44; Hb levels fell by an average of 2&#46;83<span class="elsevierStyleHsp" style=""></span>g&#47;dL in THA&#44; and 2&#46;35<span class="elsevierStyleHsp" style=""></span>g&#47;dL in TKA&#44; whereas in the control group&#44; the average Hb reduction was 3&#46;98<span class="elsevierStyleHsp" style=""></span>g&#47;dL in TKA and 3&#46;45 in THA&#46; Total bleeding was also lower in the TXA group&#58; 921<span class="elsevierStyleHsp" style=""></span>mL &#40;SD 467&#41; in THA and 969<span class="elsevierStyleHsp" style=""></span>mL &#40;498&#41; in TKA vs&#46; controls&#58; 1383<span class="elsevierStyleHsp" style=""></span>mL &#40;SD 610&#41; in THA and 1223<span class="elsevierStyleHsp" style=""></span>mL &#40;1013&#41; in TKA&#59; this difference was significant&#46; It thus follows that blood losses in patients undergoing THA and TKA and receiving TXA were 34&#37; and 21&#37; lower&#44; respectively&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the control group&#44; 5 units of RBCs &#40;RBCU&#41; were transfused compared to none in the TXA group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#60;</span><span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Two patients undergoing TKA in the control group received blood &#40;1 received 2 RBCUs&#44; and the other 3 RBCUs&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">At the end of the study&#44; there were no differences in serum Hb levels&#44; due to the use of reinfusion drains and transfusion&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The effect of surgery and TXA on clotting-fibrinolysis parameters is summarised in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; A similar increase in preoperative vs&#46; postoperative fibrinolysis parameters was observed in both surgeries&#46; In THA&#44; D dimers increased from 1004<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;SD 1056&#41; to 10&#44;248<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;4106&#41;&#44; and in ATR from 571<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;290&#41; to 6480<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;3520&#41;&#46; Similarly&#44; PAP increased from 335<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;307&#41; to 1984<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;955&#41; in THA&#44; and from 428<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;323&#41; to 1327<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;889&#41; in TKA&#46; As shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; the administration of TXA attenuates fibrinolysis&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">In contrast&#44; no differences were observed in the evolution of TAT and PAI-1 in either surgery&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Regarding complications&#44; an asymptomatic case of DVT was detected in the postoperative period in a patient undergoing THA who received TXA&#46; In this patient and 4 others&#44; CT was positive for PE&#58; 2 had received TXA&#44; and 3 had received placebo&#46; Only 1 patient presented symptomatic PE&#46; No ECG changes with respect to the preoperative period were observed&#46; The use of TXA was not associated with other complications&#44; such as deterioration of kidney function&#44; seizures&#44; nausea&#44; or abdominal pain&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">No cardiovascular complications or thromboembolic problems were detected during postoperative follow-up&#46; None of the patients in our series died during the postoperative year&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0220" class="elsevierStylePara elsevierViewall">TXA&#44; administered at the same dose&#44; achieves a comparable reduction in blood loss in patients undergoing THA and TKA&#46; Changes in fibrinolysis parameters are similar in both surgeries&#44; and this might explain why the same dose of TXA leads to a similar reduction in blood loss&#46; TXA also reduces the transfusion rate compared to placebo&#46; Finally&#44; the incidence of thromboembolic complications&#44; including subclinical events&#44; was not greater in patients treated with TXA&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Our study has shown that administration of prophylactic TXA is an effective blood saving strategy in both THA and TKA&#46; Although many studies and meta-analyses have evaluated the use of TXA in THA or TKA&#44; few have been designed specifically to compare the efficacy of this treatment in both surgeries&#46; Furthermore&#44; to the best of our knowledge&#44; no studies have hitherto evaluated both TXA effectiveness with changes in fibrinolysis&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Although the reduction in blood loss following TXA administration is similar in TKA and THA&#44; there is a slight tendency in favour of the latter&#46; This contradicts the most widely accepted hypothesis&#44; namely&#58; &#8220;TXA would be more effective in the presence of tourniquet-induced ischaemia that induces activation of local fibrinolysis through the release of tissue plasminogen activator &#40;t-PA&#41;&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> We believe that it is the aggressiveness of the surgery and volume of blood loss&#44; not ischaemia&#44; that determines the extent of fibrinolysis&#46; In our study&#44; for example&#44; blood loss in THA was slightly higher than in TKA &#40;an average of 160<span class="elsevierStyleHsp" style=""></span>mL&#41;&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">A meta-analysis in orthopaedic surgery found a correlation between the efficacy of TXA with preoperative estimates of blood loss&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">We also believe that the TXA dose will determine the effectiveness of the treatment&#46; In a recent meta-analysis in TKA&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> most of the studies included used lower doses &#40;<span class="elsevierStyleMonospace">&#60;</span>15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#41;&#44; or even single doses &#40;we repeated the dose at 3<span class="elsevierStyleHsp" style=""></span>h&#41;&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Another meta-analysis in THA<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> reported a slightly lower reduction in blood loss in the group treated with TXA than that obtained in our study &#40;mean 305 vs&#46; 462<span class="elsevierStyleHsp" style=""></span>mL in our case&#41;&#46; Single dose TXA was the norm in these studies&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Findings at the other end of the scale have also been reported&#58; a meta-analysis in TKA<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> reported a greater average reduction in blood loss than our series &#40;mean 591<span class="elsevierStyleHsp" style=""></span>mL vs&#46; 254<span class="elsevierStyleHsp" style=""></span>mL in our study&#41;&#46; The TXA dose in these studies was higher than that administered to our patients&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Considering the short half-life of TXA&#44; we conclude that higher&#44; repeated doses could be more effective&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">The tendency in the literature is towards single&#44; lower doses in THA&#44; and higher&#44; repeated doses in TKA&#46; We believe that this may explain the differences in efficacy reported&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> We also believe that the best outcome in both surgeries is achieved with the same regimen&#58; 2 doses of at least 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg TXA&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">In another clinical trial<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> in which TXA was administered at the same dose in THA and TKA&#44; the authors performed a subanalysis and found&#44; like us&#44; that the reduction in blood loss was similar in both surgeries&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The greatest reduction in blood loss was observed at 6 postoperative hours&#44; with 70&#37; and 50&#37;&#44; respectively&#44; in THA and TKA&#46; These differences are observed in external bleeding&#44; while occult bleeding &#40;supposedly non-externalised haematoma&#41; does not seem to be affected&#46; This has already been reported in TKA&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> and the same outcome can now be observed in THA&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">TXA significantly reduces transfusion needs&#46; None of the patients treated with TXA required transfusion&#44; while 5 RBSUs were required in the control group&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Knee or hip surgery promotes early fibrinolysis because hypoxia&#44; hypotension or circulating cytokines associated with tissue damage trigger the release of endothelial TPa&#44; which mediates the conversion of plasminogen to plasmin and results in fibrinolysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a> Some authors consider this to be a local phenomenon that is not detected systemically&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7&#44;16</span></a><span class="elsevierStyleSmallCaps">d</span>-Dimers appear to be the most reliable parameters in most studies evaluating fibrinolysis&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;17&#8211;19</span></a> and the same was true in our study&#46; <span class="elsevierStyleSmallCaps">d</span>-Dimer values increase from baseline as a results of surgery&#59; however&#44; TXA reduces this increase&#44; and thus attenuates fibrinolysis&#46; In the control group&#44; <span class="elsevierStyleSmallCaps">d</span>-dimers increased by up to 10- &#40;THA&#41; and 11- &#40;TKA&#41; fold over baseline levels&#46; However&#44; in patients treated with TXA&#44; <span class="elsevierStyleSmallCaps">d</span>-dimers only increased 2&#46;4- &#40;THA&#41; or 3&#46;8- &#40;TKA&#41; fold over baseline values&#46; Changes in <span class="elsevierStyleSmallCaps">d</span>-dimer values were similar in TKA vs&#46; THA patients&#46; This also contradicts the prevailing hypothesis that fibrinolysis is more intense in surgeries involving tourniquet-induced ischaemia&#46; Other authors have concluded that ischaemia induces localised fibrinolysis&#44; which only becomes systemic after release of the tourniquet&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> After reperfusion&#44; they&#44; like us&#44; observed no differences in fibrinolysis between hip surgery &#40;without ischaemia&#41; and knee surgery&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">PAP levels&#44; a marker of plasmin activation and consequently of fibrinolysis&#44; increased significantly after surgery&#44; although no differences were observed between knee and hip surgery&#46; The use of TXA also attenuates the increase in PAP values&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">PAI-1 however&#44; another fibrinolysis marker&#44; did not change during the study period in any of our groups&#44; a phenomenon already described by other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Finally&#44; TAT&#44; a marker of thrombin levels&#44; did not change significantly at any time before or after surgery&#44; even with administration of TXA&#46; Thrombin production has been proposed as a predictive marker of thrombotic complications&#44; and increases in the context of some surgeries&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Our results could suggest that major orthopaedic surgery stimulates the fibrinolysis system&#44; and that TXA can partially counteract this effect&#44; both locally and systemically&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">The use of TXA prophylaxis to reduce surgery-induced blood loss continues to be viewed with caution&#44; although there is no evidence of its involvement in thromboembolic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;23</span></a> All our patients underwent extensive postoperative imaging studies with the aim of detecting subclinical episodes of thromboembolic complications&#46; Only 1 case &#40;incidence 2&#46;3&#37;&#41; of DVT was detected&#46; The literature reports an incidence of subclinical DVT of between 17&#37; &#40;THA&#41; and 44&#46;3&#37; &#40;TKA&#41; detected with venography&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24&#44;25</span></a> The sensitivity of Doppler ultrasound&#44; however&#44; is low &#40;20&#37;&#8211;30&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>&#59; this is a limitation of our study&#44; and could partly explain the lower incidence detected&#46; We also detected 5 cases of PE &#40;incidence 11&#46;3&#37;&#41;&#46; The incidence of symptomatic PE is 1 in 300 arthroplasties&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> according to the literature&#46; The combined incidence of DVT and PE is 1&#8211;2 in every 200 cases&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> while we found an incidence of 1 in 44 cases&#59; we can find no explanation for this finding&#46; It is also important to note that DVT and PE were not more frequent in patients treated with TXA&#46; Extrapolating the data from this study&#44; a sample of more than 4500 patients would be needed to evaluate significant differences in the incidence of asymptomatic thromboembolism among patients treated with TXA or placebo&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Our study has certain limitations&#46; Fibrinolysis was determined at baseline and at 6 postoperative hours&#46; The timing of peak <span class="elsevierStyleSmallCaps">d</span>-dimer and PAP levels is unknown&#59; we cannot therefore be certain that analysing PAI-1 and TAT levels at a later time point would detect differences with respect to the baseline values&#46; Given the cost involved&#44; we chose to perform a single determination at 6 postoperative hours&#44; which is the time margin used in several reference studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;18&#44;19</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">The most important limitation of our study is the limited size of the sample&#44; which prevents us from drawing firm conclusions on the safety of TXA&#46; The sample size was calculated on the basis of the primary endpoint&#44; which was the reduction of transfusion requirements&#46; We did not evaluate study patients for the presence of asymptomatic thromboembolism at the time of admission&#44; and we did not perform imaging studies to detect asymptomatic PE and DVT after the fourth postoperative day&#46; In this regard&#44; although the origin of clinically relevant thrombosis is found in subclinical events in the early postoperative period&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> the risk persists for weeks&#46; In addition&#44; as mentioned above&#44; ultrasound has low sensitivity for the detection of DVT&#46; Computed tomography&#44; however&#44; has the highest sensitivity for PE&#46; We attempted to overcome these limitations by extending the period of postoperative follow-up to 1 year&#44; using the patient&#39;s clinical history and hospital records&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Further studies are needed to ascertain the most effective TXA regimen&#46; We suggest that high doses may reduce blood loss&#44; but this should probably be weighed up against the risk of thrombosis&#46; Undoubtedly&#44; a large study is needed to clarify the efficacy and safety of different dosing regimens&#46; Some promising initiatives have already been started in this regard&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> While awaiting the results of these trials&#44; studies such as ours&#44; which provide safety data based on highly sensitive tests applied systematically to all patients&#44; can provide data for future meta-analyses</p><p id="par0325" class="elsevierStylePara elsevierViewall">In conclusion&#44; the prophylactic administration of the same dose of TXA shows a similar reduction in postoperative blood loss in both hip and knee arthroplasty&#46; The fibrinolysis parameters did not differ between surgeries&#44; although some TXA-induced changes were observed&#46; Finally&#44; despite the antifibrinolytic effect of TXA&#44; the prospective study with ultrasound and CT was unable to detect a higher incidence of thromboembolic complications with respect to the control group&#44; although our study was not designed to obtain definitive conclusions in this regard&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0330" class="elsevierStylePara elsevierViewall">This study was funded by an FIS grant from the <span class="elsevierStyleGrantSponsor" id="gs1">Carlos III Institute</span>&#44; Madrid <span class="elsevierStyleItalic">&#40;FIS 2006&#47;1227&#41;&#46;</span></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interest</span><p id="par0335" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          "identificador" => "xres1196192"
          "titulo" => "Resumen"
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            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objetivo"
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              "identificador" => "abst0030"
              "titulo" => "M&#233;todo"
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            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
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              "identificador" => "abst0040"
              "titulo" => "Conclusiones"
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          "identificador" => "xpalclavsec1114591"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Material and methods"
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            0 => array:2 [
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              "titulo" => "Statistical analysis"
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          "identificador" => "sec0020"
          "titulo" => "Results"
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          "identificador" => "sec0025"
          "titulo" => "Discussion"
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          "identificador" => "sec0030"
          "titulo" => "Funding"
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        9 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflicts of interest"
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        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-09-14"
    "fechaAceptado" => "2019-01-25"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1114590"
          "palabras" => array:6 [
            0 => "Blood-loss"
            1 => "Blood-transfusion"
            2 => "Blood-coagulation"
            3 => "Thrombosis"
            4 => "Knee replacement"
            5 => "Hip replacement"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1114591"
          "palabras" => array:6 [
            0 => "Sangrado"
            1 => "Transfusi&#243;n sangu&#237;nea"
            2 => "Coagulaci&#243;n"
            3 => "Trombosis"
            4 => "Artroplastia de cadera"
            5 => "Artroplastia de rodilla"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tourniquet-induced ischaemia could increase fibrinolysis and enhance tranexamic acid &#40;TXA&#41; efficacy in total knee arthroplasty &#40;TKA&#41; compared to total hip arthroplasty &#40;THA&#41;&#46; The aims of this study are to compare the effect of TXA on bleeding and fibrinolysis in both types of surgery&#44; and to record thromboembolic complications&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective double-blind study was conducted on patients scheduled for TKA or THA who received TXA &#40;2 bolus of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; or placebo&#46; Bleeding and fibrinolysis were evaluated&#46; Doppler-ultrasound and computed tomography were performed in order to assess any thromboembolic complications&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 44 patients were included &#40;11 THA and 11 TKA treated with TXA&#59; 11 THA and 11 TKA as controls&#41;&#46; Blood losses were significantly lower in the TXA group &#40;mean 921<span class="elsevierStyleHsp" style=""></span>mL vs 1383<span class="elsevierStyleHsp" style=""></span>mL in THA and 969<span class="elsevierStyleHsp" style=""></span>mL vs 1223<span class="elsevierStyleHsp" style=""></span>mL in TKA&#41;&#44; and no transfusions were needed with TXA&#44; whereas 5 blood units were transfused in controls&#46; TXA was equally effecting in reducing bleeding in both surgeries &#40;33&#37; in THA and 21&#37; in TKA&#41;&#46; The significant mean increase in <span class="elsevierStyleSmallCaps">d</span>-dimers from baseline to 6<span class="elsevierStyleHsp" style=""></span>h after surgery &#40;1004<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L to 10&#44;284<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in THA and 571<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L to 6480<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in TKA&#41; was attenuated by TXA &#40;1077<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L to 2590<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in THA and 655<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L to 2535<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in TKA&#41;&#46; There were no differences in thromboembolic episodes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Prophylactic use of tranexamic acid is equally effective in reducing bleeding in TKA and THA&#46; Both surgeries have a similar effect on fibrinolysis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La isquemia derivada de la aplicaci&#243;n del torniquete es un factor fibrinol&#237;tico que podr&#237;a potenciar la eficacia del &#225;cido tranex&#225;mico &#40;ATx&#41; en artroplastia total de rodilla &#40;ATR&#41; frente a la artroplastia total de cadera &#40;ATC&#41;&#46; Nuestro objetivo es comparar el efecto del ATx sobre sangrado y fibrin&#243;lisis en estas 2 artroplastias&#44; valorando la incidencia de complicaciones&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Ensayo cl&#237;nico prospectivo&#44; aleatorizado y doble ciego&#46; Los pacientes programados para ATR o ATC recib&#237;an ATx &#40;2 infusiones 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; o placebo&#46; Se cuantific&#243; sangrado y par&#225;metros de fibrin&#243;lisis&#44; y se detectaron complicaciones tromboemb&#243;licas con ecograf&#237;a doppler y tomograf&#237;a computarizada&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Fueron incluidos 44 pacientes &#40;11 ATC y 11 ATR tratados con ATx&#59; 11 ATC y 11 ATR fueron controles&#41;&#46; El sangrado fue significativamente menor en el grupo tratado con ATx &#40;promedio 921<span class="elsevierStyleHsp" style=""></span>mL vs&#46; 1383<span class="elsevierStyleHsp" style=""></span>mL en ATC y 969<span class="elsevierStyleHsp" style=""></span>mL vs&#46; 1223<span class="elsevierStyleHsp" style=""></span>mL en ATR&#41; y se necesitaron menos transfusiones &#40;ninguna frente a 5 unidades en grupo control&#41;&#46; El ATx fue igualmente eficaz en la reducci&#243;n del sangrado en ambas cirug&#237;as &#40;reducci&#243;n del 33&#37; en ATC y del 21&#37; en ATR&#41;&#46; El gran incremento medio de d&#237;mero D entre el periodo basal y las 6<span class="elsevierStyleHsp" style=""></span>h &#40;1&#46;004 a 10&#46;284<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L en ATC y 571 a 6&#46;480<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L en ATR&#41; es atenuado por el uso de ATx &#40;1&#46;077 a 2&#46;590<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L en ATC y 655 a 2&#46;535<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L en ATR&#41;&#46; No hubo diferencias significativas en eventos tromboemb&#243;licos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El ATx profil&#225;ctico es igualmente efectivo en ATR y ATC para reducir sangrado&#46; Ambas cirug&#237;as tienen efecto similar sobre la fibrin&#243;lisis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Alvarez J&#44; Santiveri FJ&#44; Ramos MI&#44; Gallart L&#44; Aguilera L&#44; Puig-Verdie L&#46; Ensayo cl&#237;nico sobre el efecto del &#225;cido tranex&#225;mico en el sangrado y la fibrin&#243;lisis durante la artroplastia simple de cadera y rodilla&#46; Rev Esp Anestesiol Reanim&#46; 2019&#59;66&#58;299&#8211;306&#46;</p>"
      ]
    ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2069
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            "Tamanyo" => 312403
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study flow chart&#46;</p>"
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      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; Hb&#58; haemoglobin&#59; HCT&#58; haematocrit&#59; INR&#58; international normalised ratio&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Data shown as numbers &#40;<span class="elsevierStyleItalic">n</span>&#41; or means &#40;SD&#41;&#46; No statistical differences&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">70 &#40;12&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#46;4 &#40;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">72&#46;4 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Men&#47;women &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;2 &#40;6&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">29&#46;1 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;6 &#40;8&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;1 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASA II&#47;III&#47;IV &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#47;3&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#47;3&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#47;6&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#47;4&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Hb &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#46;7 &#40;0&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;4 &#40;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;7 &#40;0&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;0 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCT &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;7 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;5 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;7 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;5 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelets &#40;&#215;10<span class="elsevierStyleSup">3</span><span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">&#8722;3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">258 &#40;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">221 &#40;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">237 &#40;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">240 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;06 &#40;0&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;07 &#40;0&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;10 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;07 &#40;1&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total hip arthroplasty</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total knee arthroplasty</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surgery time &#40;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Volume of crystalloids &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">562 &#40;338&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">541 &#40;403&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">680 &#40;343&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">700 &#40;436&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Volume of colloids &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">283 &#40;252&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">495 &#40;436&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140 &#40;227&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">259 &#40;252&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood loss &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">347 &#40;155&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">440 &#40;152&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8776;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8776;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR at end of surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrinogen at end of surgery &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">432 &#40;146&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">466 &#40;252&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">475 &#40;156&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">356 &#40;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Hb&#58; haemoglobin&#59; HTC&#58; haematocrit&#59; RBCUs&#58; units of packed red blood cells&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">The data are shown as mean &#40;SD&#41; or number of episodes &#40;<span class="elsevierStyleItalic">n</span>&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total hip arthroplasty</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total knee arthroplasty</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hb 96 postoperative hours &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;7 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;6 &#40;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;2 &#40;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;6 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTC 96 postoperative hours &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;1 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;5 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;9 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;1 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in Hb 6 postoperative hours &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;12 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;77 &#40;0&#46;1&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;94 &#40;0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;38 &#40;0&#46;59&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in Hb 96 postoperative hours &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;98 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;83 &#40;1&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;45 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;35 &#40;1&#46;1&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood from reinfusion drain &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">449 &#40;335&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">190 &#40;167&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">518 &#40;339&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">392 &#40;376&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estimated blood loss at 96 postoperative hours &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1383 &#40;610&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">921 &#40;467&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1223 &#40;1013&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">969 &#40;498&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estimated occult blood loss &#40;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">988 &#40;736&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">730 &#40;377&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">705 &#40;864&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">577 &#40;333&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Allogeneic transfusion &#40;RBCUs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deep vein thrombosis &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pulmonary embolism &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">PAI-1&#58; type 1 plasminogen activator inhibitor&#59; PAP&#58; plasmin-antiplasmin complexes&#59; POST&#58; postoperative&#59; PRE&#58; preoperative&#59; TAT&#58; thrombin-antithrombin complexes&#59; APTT&#58; activated partial thromboplastin time&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Values shown as means &#40;SD&#41;&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total hip arthroplasty</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total knee arthroplasty</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TXA group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;06 &#40;0&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;07 &#40;0&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;67 &#40;3&#46;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;07 &#40;1&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;89 &#40;0&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;13 &#40;0&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;13 &#40;0&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;14 &#40;0&#46;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TTPA ratio</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;78 &#40;4&#46;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;89 &#40;4&#46;98&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;69 &#40;4&#46;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;09 &#40;4&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;13 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;90 &#40;0&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9 &#40;0&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;09 &#40;0&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrinogen &#40;mg&#47;&#62;dL&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">389 &#40;101&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">383 &#40;138&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">415 &#40;124&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">385 &#40;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">334 &#40;81&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">411 &#40;189&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">369 &#40;110&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">338 &#40;130&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSmallCaps">d</span>-Dimer &#40;&#956;g&#47;L&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1004 &#40;1056&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1077 &#40;540&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">571 &#40;290&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">655 &#40;361&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;248 &#40;4106&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2590 &#40;1765&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6480 &#40;3520&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2535 &#40;1280&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAP &#40;&#956;g&#47;L&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">335 &#40;307&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">479 &#40;360&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">428 &#40;323&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">324 &#40;109&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1984 &#40;955&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1172 &#40;448&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1327 &#40;889&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">936 &#40;454&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TAT &#40;&#956;g&#47;L&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#46;4 &#40;30&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;27&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;2 &#40;20&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;8 &#40;33&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">POST 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#46;4 &#40;75&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;2 &#40;23&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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