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Letter to the Editor
Anticoagulation as a confounding factor in the diagnosis of acquired hemophilia
Anticoagulación como factor de confusión en el diagnóstico de una hemofilia adquirida
Rocío Cabra Rodrígueza,
Corresponding author
rocarod@hotmail.com

Corresponding author.
, María José Ruíz Márquezb
a UGC Centro de Salud Alamillo, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain
b Servicio de Análisis Clínicos. Hospital de Riotinto, Minas de Riotinto, Huelva, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acquired haemophilia &#40;AH&#41; is an autoimmune coagulopathy that predisposes to haemorrhagic events&#44; caused by the production of specific circulating autoantibodies that inhibit some of the clotting factors&#46; Frequently these autoantibodies are directed against coagulation factor <span class="elsevierStyleSmallCaps">viii</span> &#40;FVIII&#41; &#40;AH A &#91;AHA&#93;&#41; or coagulation factor <span class="elsevierStyleSmallCaps">IX</span> &#40;acquired haemophilia B&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The incidence of AH is estimated to be 1&#8211;3 cases per million inhabitants per year&#44; with a mean age of around 65 years upon presentation&#46; Although it has been related to certain clinical conditions &#40;pregnancy or the post-partum period&#44; autoimmune diseases&#44; infections&#44; drugs&#44; cancer&#41;&#44; AH is considered idiopathic in 50&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of an 82-year-old man with permanent atrial fibrillation anticoagulated with Sintrom&#174; &#40;Rovi Pharma Industrial Services&#44; SA&#59; local representative&#58; Norgine de Espa&#241;a SLU&#41;&#46; The anticoagulation treatment was temporarily halted due to a hematoma in the lower limb&#44; which was related to an overdose of oral anticoagulants &#40;OAC&#41;&#46; The patient was admitted due to extensive spontaneous hematoma in the right pectoral region which extended to the lateral cervical region and presented with pain&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">When the patient was examined&#44; he said the region felt sore when touched although there were no signs of superinfection&#46; The first analytical study from the Emergency Department showed haemoglobin 12&#46;1&#8239;g&#47;dl &#40;12&#8722;16&#8242;&#41;&#44; leukocytes 10&#8239;&#215;&#8239;10<span class="elsevierStyleSup">3</span>&#47;&#956;l &#40;5&#46;00&#8211;14&#46;50&#41;&#44; segmented 79&#46;1&#37; &#40;25&#46;00&#8211;65&#46;00&#41;&#44; lymphocytes 13&#46;7&#37; &#40;20&#46;00&#8211;53&#46;00&#41;&#44; platelets 285&#8239;&#215;&#8239;10<span class="elsevierStyleSup">3</span>&#47;&#956;l &#40;130&#8211;450&#41;&#44; folic acid 2&#46;24&#8239;ng&#47;ml &#40;6&#46;5&#8211;38&#46;4&#41;&#46; Prothrombin time &#40;PT&#41; ratio and PT &#40;INR&#41; were normal&#46; The activated partial thromboplastin time &#40;APTT&#41; was elevated&#44; with a ratio of 2&#46;02&#44; which corrected with normal&#44; non-incubated plasma and which was prolonged in the incubated mix with the absence of lupus anticoagulant&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A cervical ultrasound showed compatibility with a hematoma in the right supraclavicular region&#44; with approximate dimensions of 11&#8239;&#215;&#8239;4&#8239;cm&#46; Other tests were conducted including a haematological study of haemostasis-fibrinolysis&#44; which showed&#58; APTT &#40;ratio&#41;&#58; 2&#46;83 ratio &#40;0&#46;70&#8211;1&#46;20&#41;&#44; APTT &#40;1 patient&#8239;&#43;&#8239;1 normal&#59; ratio&#41;&#58; 1&#46;51 ratio &#40;0&#46;70&#8211;1&#46;20&#41;&#44; FVIII &#40;coagulative&#41;&#58; 4&#46;7&#37; &#40;60&#46;0&#8211;160&#46;0&#41;&#44; factor <span class="elsevierStyleSmallCaps">xii</span> &#40;coagulative&#41;&#58; 53&#46;1&#37; &#40;60&#46;0&#8211;150&#46;0&#41;&#44; with normal levels of the rest of the coagulation factors and quantification of the specific FVIII inhibitor&#58; 7&#46;5 Bethesda units&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally&#44; the patient was diagnosed with acquired haemophilia A and folic acid deficiency&#44; since the FVIII inhibitor study was positive&#46; The treatment indicated was oral prednisone for 4 weeks in a descending regimen&#46; Initially&#44; a 2 dose of FVII &#40;eptacog &#945; activated&#41; and tranexamic acid had to be administered&#59; the latter as a one off&#44; due to the thrombotic risk in this patient&#46; The response was favourable with the hematoma evolving without evidence of neurovascular compression or superinfection and giving a negative result to the specific FVIII inhibitor study&#46; Therefore&#44; oral anticoagulation was able to be reintroduced early since the patient was at high cardiovascular risk&#46; Finally&#44; the folic acid deficit was corrected with oral supplementation&#46; The follow-up of the patient by the Haematology department has revealed no signs of relapse to date&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">AHA can present with severe bleeding disorder in approximately 20&#8211;30&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is found in people without a history of bleeding disorders and is a rare cause of bleeding diathesis&#46; 10&#37; of patients do not present bleeding and&#44; therefore&#44; a prolonged APTT should never be ignored prior to performing any invasive procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">AHA should be suspected when there is an elongated APTT that cannot be corrected with normal plasma and normal PT&#46; In addition&#44; a reduction should be detected in functional FVIII&#8239;&#60;&#8239;50&#37;&#44; with levels of the rest of the coagulation factors in the normal range&#44; presence of the anti-FVIII inhibitor &#8805; 0&#46;6 Bethesda units&#47;ml&#44; preferably by the Nijmegen Bethesda method &#40;recommended by the International Society on Thrombosis and Haemostasis&#41;&#44; absence of LA and other coagulopathies&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In the case of our patient&#44; elongation of the APTT that corrected immediately with normal plasma but did not in the incubated mixture raised the suspicion of the presence of a slow-reacting or time-dependent inhibitor &#40;most of the FVIII inhibitors and 8&#37; of LAs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Preanalytical aspects that make it difficult to correctly identify AHA have been described&#44; which include OACs&#44; causing reduced levels of most coagulation factors and an inhibitory test pattern as a consequence of said treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This would explain the difficulty of a correct diagnosis when faced with the first episode of hematoma in our patient&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The prevention and control of bleeding is recommended in AHA&#44; starting treatment with activated recombinant FVII&#44; activated prothrombin complex or recombinant porcine FVIII&#44; and the eradication of autoantibodies&#44; using corticosteroid therapy&#44; cyclophosphamide and rituximab&#44; or combinations of the same&#46; In addition&#44; an individualised evaluation of the immunosuppressive therapy is necessary to minimise the adverse effects in frail patients&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The pharmacological approach in these patients constitutes an important medical challenge&#44; many of whom are anticoagulated due to a high thrombotic risk&#44; and we have to balance the risk of thrombosis and bleeding in frail patients with high comorbidity&#46;</p></span>"
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ISSN: 23870206
Original language: English
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