Case report
Epidural analgesia in a patient with factor XI deficit
Analgesia epidural en paciente con déficit de factor XI
R. López Herrero, B. Sánchez Quirós, R.P. Rodríguez Jiménez
, H. Muñoz Hernández
Corresponding author
Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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López Herrero, B. Sánchez Quirós, R.P. Rodríguez Jiménez, H. Muñoz Hernández" "autores" => array:4 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "López Herrero" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Sánchez Quirós" ] 2 => array:4 [ "nombre" => "R.P." "apellidos" => "Rodríguez Jiménez" "email" => array:1 [ 0 => "rociolopezherrero@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:2 [ "nombre" => "H." "apellidos" => "Muñoz Hernández" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Analgesia epidural en paciente con déficit de factor XI" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1257 "Ancho" => 2167 "Tamanyo" => 110822 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Factor XI levels in IU/dl throughout the delivery process.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Factor XI deficiency is an inherited haemorrhagic disease characterised by a decreased level or activity of factor XI due to a mutation in the F11 gene (4q35). It is inherited autosomal with variable penetrance.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is a rare disorder with an incidence of 1/1,000,000 in the general population,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and is most prevalent in Ashkenazi Jews, with a heterozygous frequency of 8%.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Factor XI deficiency can be diagnosed after bleeding or incidentally in a blood test, by the presence of a prolonged activated partial thromboplastin time (aPTT). Normal levels are between 70 and 150 IU/dl. Factor deficiency causes a bleeding tendency that is unpredictable and not necessarily related to factor levels.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Treatment will depend on factor values and will be primarily with fresh frozen plasma (FFP) and tranexamic acid or factor XI.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">FFP is effective in increasing factor levels. It is administered at a dose of 20 ml/kg. It has a half-life of 60−80 h and has a small risk of complications such as virus transmission, transfusion-associated lung injury (TRALI) or allergic reaction.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Tranexamic acid is used to prevent bleeding during procedures.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Factor XI presents a high risk of thrombogenicity. It is administered at doses of 10−15 UI/kg. Pregnant women have a procoagulant state that may be increased if factor XI is administered. For this reason, antithrombotic prophylaxis should be carried out and early mobilisation should be encouraged, and it should be avoided in combination with tranexamic acid. Thromboembolic events secondary to the administration of this factor have been described, even with levels administered below 30 IU/kg, such as disseminated intravascular coagulation, pulmonary thromboembolism and cerebrovascular events.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Women with factor XI deficiency are at increased risk of uterine bleeding during labour, and for this reason special considerations need to be taken into account.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> We present a case of a pregnant woman with factor XI deficiency undergoing epidural analgesia for labour.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0030" class="elsevierStylePara elsevierViewall">She was a 36-year-old first time mother with a history of haemophilia type C (partial factor XI deficiency with baseline levels of 26%) and no personal history of bleeding. Pregnancy was controlled with multidisciplinary monitoring by haematology, anaesthesiology and gynaecology. The patient attended a pre-anaesthesia consultation to learn about the possible analgesic options for her clinical situation. After this consultation, despite being offered other analgesic alternatives, she decided to undergo epidural analgesia, fully understanding the high risk of possible epidural haematoma secondary to the technique, as well as the presence of possible side effects derived from the transfusion of a high volume of FFP, such as an acute pulmonary lesion associated with the transfusion. At the patient's request, it was decided, in consensus with haematology and obstetrics, to schedule induction of labour at 38 weeks' gestation in order to be able to carry out adequate coagulation control and correct the factor deficit before epidural analgesia was performed. It was decided that the minimum factor XI levels necessary to be able to perform this technique should be higher than 40 UI/dl.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Before starting induction of labour, factor XI levels were determined and were 28.5 UI/dl. In the presence of values below 40% it was decided to transfuse 15 ml/kg FFP. During the transfusion, an episode of urticaria occurred, which was reported to the haematology department, and the transfusion rate was slowed down. After 24 h of FFP perfusion, factor levels were determined to be 29.5 UI/dl, so it was decided to transfuse 5 ml/kg of FFP. After transfusion, levels of 45.5 UI/dl were obtained, and we thus began induction of labour, and epidural analgesia was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The location of the epidural space was performed without incident at the first attempt. We started perfusion with local anaesthetic (ropivacaine .2% at 7 ml/h), obtaining an adequate analgesic level. After two hours of active expulsion, a Kiwi type vacuum cup was applied without incident. After delivery, 1 g of tranexamic acid was administered every 8 h for the first 24 h. The patient did not have excessive bleeding (500 ml), so no FFP or factor XI was required. After delivery, factor levels were 40.3%, so the epidural catheter was removed. She also had no postpartum bleeding or complications related to epidural analgesia.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Pregnant women with factor deficiency are at high risk of bleeding during labour and in the immediate postpartum period. Factor levels do not change significantly during pregnancy,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> as in our patient, who presented at 38 weeks of gestation (29.5 UI/dl) with levels similar to baseline (28.5 UI/dl).</p><p id="par0045" class="elsevierStylePara elsevierViewall">It is necessary to have a therapeutic management plan that will depend on the factor levels obtained in the third trimester of gestation. There are different guidelines for its management, but there is no clear consensus among them, as the existing bibliography is scarce. One of them is the British Committee for Standards in Haematology (BCSH) Guidelines for the Management of Factor XI Deficiency, from which the following recommendations can be extracted<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>):<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">□</span><p id="par0050" class="elsevierStylePara elsevierViewall">Presence of Factor XI activity <15 UI/dl: we should consider administering factor XI concentrate at a dose of 10−15 UI/kg; if not available, administer 15−25 ml/kg FFP at the onset of labour or before induction or caesarean section, associated with tranexamic acid (15−20 mg/kg). The goal is to maintain factor levels above 30 U/dl during labour and for 3−4 days thereafter in the case of vaginal delivery or 6−7 days if a caesarean section was performed.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">□</span><p id="par0055" class="elsevierStylePara elsevierViewall">Factor activity between 15 and 50 UI/dl and previous history of bleeding: tranexamic acid can be administered orally or intravenously 1 g every 6−8 h for 5−7 days after delivery. This period is variable and will depend mainly on the degree of bleeding.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">□</span><p id="par0060" class="elsevierStylePara elsevierViewall">Factor activity between 15 and 50 UI/dl with no previous history of bleeding: only consider treatment with factor XI, FFP and tranexamic acid if abnormal bleeding occurs.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">□</span><p id="par0065" class="elsevierStylePara elsevierViewall">Whenever an invasive procedure is to be performed, levels above 40 UI/dl are required.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">□</span><p id="par0070" class="elsevierStylePara elsevierViewall">In the postpartum period, tranexamic acid can be administered. Its administration and duration will depend on whether or not the patient has significant bleeding.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li></ul></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Pain during the labour period can be controlled by inhalation analgesia, continuous perfusion of remifentanil or neuroaxial techniques. The use of neuroaxial analgesia in patients with coagulation disorders is controversial due to the increased risk of epidural haematoma leading to spinal cord compression and paraplegia. Epidural analgesia may be performed if the patient has no previous history of bleeding and if she has factor XI levels above 40 UI/dl after administration of 20 ml/kg FFP.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0080" class="elsevierStylePara elsevierViewall">The management of pregnant patients with severe coagulation disorders is challenging. Decisions should be made by an experienced multidisciplinary team including obstetricians, haematologists and anaesthesiologists. Management decisions should be individualised, taking into account factor levels in the third trimester of gestation, as well as the presence or absence of a personal history of bleeding. Epidural analgesia can be considered safe in pregnant women with factor XI levels above 40 UI/dl and prior administration of 20 ml/kg FFP.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Funding</span><p id="par0085" class="elsevierStylePara elsevierViewall">This study did not receive any grants from financial public, commercial or not-for-profit entities.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1860767" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1617464" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1860766" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1617465" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-02-20" "fechaAceptado" => "2021-09-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1617464" "palabras" => array:3 [ 0 => "Factor XI deficiency" 1 => "Pregnancy" 2 => "Epidural analgesia" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1617465" "palabras" => array:3 [ 0 => "Déficit factor XI" 1 => "Analgesia epidural" 2 => "Embarazo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">FXI deficiency is a rare bleeding disorder characterised by a decreased level or activity of factor. Pregnant women are at increased risk of uterine bleeding during childbirth. Neuroaxial analgesia may increase the risk of epidural hematoma in these patients. However, there is no consensus on the anaesthetic management.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We present the clinical case of a 36-year-old woman with a personal history of factor XI deficiency, pregnant with 38 weeks gestation who is scheduled to perform birth induction. Pre-induction factor levels were measured. They were less than 40%, so it was decided to transfuse 20 ml/kg of fresh frozen plasma. After the transfusion it had levels greater than 40%, so epidural analgesia was performed without incident. The patient had no complications secondary to epidural analgesia or transfusion of a high volume of plasma.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El déficit de factor XI es una enfermedad hemorrágica rara que se caracteriza por presentar disminución del nivel o de la actividad del factor. Las mujeres embarazadas con esta patología presentan mayor riesgo de sangrado uterino durante el parto. El uso de analgesia neuroaxial en estas pacientes puede aumentar el riesgo de producir hematoma epidural. Es necesario realizar un seguimiento multidisciplinar en el que participen activamente Anestesiólogos, Hematólogos y Ginecólogos. Actualmente disponemos de escasa bibliografía sobre el manejo anestésico de este tipo de patología.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Presentamos el caso clínico de una mujer de 36 años con antecedentes personales de déficit de factor XI, embarazada de 38 semanas de gestación que es programada para realización de inducción del parto. Previa a la inducción se midieron los niveles del factor siendo inferiores al 40%, por lo que se decidió transfundir 20 ml/kg de plasma fresco congelado. Tras la transfusión presentó niveles superiores al 40%, por lo que se realizó analgesia epidural sin incidencias. La paciente no presentó complicaciones secundarias a la analgesia epidural ni a la transfusión de un volumen elevado de plasma.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1257 "Ancho" => 2167 "Tamanyo" => 110822 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Factor XI levels in IU/dl throughout the delivery process.</p>" ] ] 1 => array:9 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Modified from Myers B, Pavord S. Comments on “Management of parturients with Factor XI deficiency - 10 year case series and review of the literature”. Eur J Obstet Gynecol Reprod Biol. 2017;217:176." "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2627 "Ancho" => 2500 "Tamanyo" => 444114 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Peripartum and postpartum management of factor XI deficient patient.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Gómez" 1 => "P. 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