|Year : 2013 | Volume
| Issue : 1 | Page : 37-39
Anaesthesia management of caesarean section in a patient with severe factor XI deficiency
Debesh Bhoi, EJ Sreekumar, Rahul Kumar Anand, Dalim Kumar Baidya, Anjolie Chhabra
Department of Anaesthesia, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||1-Jul-2013|
Departments of Anaesthesia and Intensive Care, 5th Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Factor XI deficiency is a rare coagulation disorder associated with bleeding tendency and prolonged APTT. Parturients can have increased bleeding during vaginal delivery or cesarean section. Patients with severe factor XI deficiency should receive prophylactic fresh frozen plasma or factor XI transfusion in the peripartum period to maintain a near normal APTT. Limited evidence based on case reports and series is inconclusive as to the choice of anesthesia technique for cesarean section. We describe the anesthesia management of a parturient with severe factor XI deficiency for cesarean section and discuss the relevant literature.
Keywords: Anesthesia, cesarean section, factor XI deficiency
|How to cite this article:|
Bhoi D, Sreekumar E J, Anand RK, Baidya DK, Chhabra A. Anaesthesia management of caesarean section in a patient with severe factor XI deficiency. J Obstet Anaesth Crit Care 2013;3:37-9
|How to cite this URL:|
Bhoi D, Sreekumar E J, Anand RK, Baidya DK, Chhabra A. Anaesthesia management of caesarean section in a patient with severe factor XI deficiency. J Obstet Anaesth Crit Care [serial online] 2013 [cited 2019 Sep 23];3:37-9. Available from: http://www.joacc.com/text.asp?2013/3/1/37/114292
| Introduction|| |
Factor XI deficiency is a rare inherited coagulation disorder which is associated with prolonged activated partial thromboplastin time (APTT) and bleeding tendency. First described in 1953,  it commonly presents with unexpected bleeding during surgical procedures or after a traumatic injury. Factor XI levels usually remain unchanged throughout the pregnancy.  However, severe deficiency (factor level < 15%) may present with bleeding tendency.  We report the peri-operative anesthesia management of a parturient with severe factor XI deficiency for cesarean section and discuss the relevant literature.
| Case Report|| |
A 30-year-old 70 kg pregnant female (gravida 2, para 2) was referred to our institute in her second trimester due to prolonged APTT. She had spontaneous conception and was under regular antenatal check-up. In the second trimester, she developed easy bruisability. There was a history of secondary post-partum hemorrhage due to complete perineal tear 6 years back during her previous pregnancy which was managed with transfusion of packed cells and fresh frozen plasma (FFP). Coagulation profile revealed prolonged APTT (control/test 26/120 s). However, prothrombin time (PT 11.5/12.7 s) and thrombin time (TT 13/13.4) were normal. Other routine laboratory investigations triple screening and level 2 ultrasound were normal. On further evaluation, factor XI activity was found to be 3% (Normal 70-120%). Other coagulation factors assays revealed normal factor VIII, IX, and XII.
She continued regular follow-up in Obstetrics and Hematology Department and was planned for elective cesarean section at 37 th week. On examination, her pulse was 80/min, blood pressure 110/70 mmHg, other systemic and airway examination was unremarkable. APTT on the day before surgery was 30/76 s and PT (12/13 s) TT (15/16 s) and platelet count (189 lakhs/mm 3 ) were all normal. Hematology consultation was obtained, and she was transfused 6 units FFP (each unit approximately 200 ml) in the night before surgery.
On the morning of surgery, APTT was 27/33.6 s. Anti-aspiration prophylaxis was administered, and surgery was planned under general anesthesia. In the operating room, two wide bore intravenous accesses were obtained, and routine monitoring was attached. Rapid sequence induction of anesthesia was performed with thiopentone sodium 300 mg and succinylcholine 100 mg. Trachea was intubated with 7.5 mm cuffed endotracheal tube and mechanical ventilation was facilitated with vecuronium. Anesthesia was maintained with oxygen, nitrous oxide, and isoflurane. A healthy male baby weighing 3.87 kg was delivered with an Apgar score of 8 and 9 at 1 min and 5 min respectively. Fentanyl 150 mcg was given for analgesia. Oxytocin 20 unit was slowly infused over 1 h. Intra-operative blood loss was 600 ml; ringer lactate 2.0 l and 2 unit of FFP were transfused. Urine output was 250 ml. Abdomen was closed after achieving proper hemostasis and a drain was left in situ. At the end of surgery, residual neuromuscular blockade was reversed, trachea was extubated, and she was shifted to post anesthesia care unit (PACU). Another 4 unit FFP were transfused in PACU. On the next day, APPT was 30/44. However, she was transfused 6 units FFP every day until 5 th post-operative day along with daily APTT monitoring as advised by Hematologist. Her APTT remained within 1-1.5 times of control and abdominal drain was removed on 3 rd post-operative day. Factor XI assay on 5 th day revealed 15% activity. She was discharged home with a baby on 7 th post-operative day.
| Discussion|| |
Factor XI deficiency, also known as "hemophilia C," "plasma thromboplastin antecedent deficiency" or "Rosenthal syndrome" occurs due to defect in the gene encoding factor XI located on the distal arm of chromosome 4 (4q35). , It is synthesized in the liver and circulates in plasma as a complex with high-molecular weight kininogen with a half-life of about 52 h.  This is a rare bleeding disorder with incidence of 1/million and predominantly found in Ashkenazi Jews with a heterozygous frequency of 9% and a homozygous frequency of 0.22%. 
APTT is prolonged when any factor involved in the intrinsic pathway decreases below 30% of normal. Severe factor XI deficiency is defined as levels <15%. These patients usually have plasma factor level <15-20 IU/dl, and they have homozygous or compound heterozygous mutations. Partially deficient individuals are heterozygous with factor level 15-70%.  However, plasma level of factor XI does not correlate with bleeding tendency and there may not be excessive bleeding in patients with severe deficiency. This is because bleeding risk is more dependent on the amount of factor XI in platelets than in plasma. Moreover, spontaneous bleeding in isolated factor XI deficiency is not very common and associated deficiency of other factor, most commonly von Willibrand factor should be ruled out.
It has been observed that, factor XI level usually decreases during the pregnancy, but the evidence is lacking and recent reports indicate that there may be no change during the pregnancy.  In parturient with partial or severe factor XI deficiency, excessive bleeding can occur during vaginal delivery or cesarean section. Routine monitoring of coagulation parameters and preferably factor XI should be carried out at confirmation of pregnancy and in the later part of pregnancy. Any co-existing von Willebrand factor deficiency or platelet function disorders are evaluated if spontaneous bleeding occurs. In the present case, severe factor XI deficiency was diagnosed, and the coagulation monitoring was serially performed in the 3 rd trimester and peripartum period. Other individual factor deficiencies were also ruled out.
According to guidelines by United Kingdom Hemophilia Center Doctors' Organization, the patients with severe factor XI deficiency (levels < 15 IU/dl) should receive prophylactic transfusion of factor XI concentrate or FFP at the onset of labor or prior to planned induction of labor or cesarean section. The level should be maintained at 30 IU/dl or more during labor and for 3-4 days after vaginal delivery and 6-7 days after cesarean section.  Factor XI concentrate should be given at a dose of 15 U/kg with careful monitoring for thrombotic complications and peak level should not exceed 70 IU/dl.  If factor XI concentrate is not available FFP should be used at a dose of 10-20 ml/kg.  When the APTT is normalized in these patients, the factor XI level usually reaches 25-30%, which is sufficient for hemostasis.  In our patient, FFP was transfused 15 ml/kg/day during the perioperative period starting from 1 day prior to surgery until 5 th post-operative day. Her APTT was within 1-1.5 times of control and factor XI assay showed 15% activity on post-operative day 5 without any clinical bleeding.
Recombinant factor VIIa has also been proposed as a treatment for various coagulation factor deficiencies. This has been prophylactically used in patients with factor XI deficiency to prevent the surgical bleeding. However, extreme caution should be exercised against risk of thrombosis. 
In a series of 13 pregnant patients with factor XI deficiency, Singh et al. described the anesthesia techniques. A total of 9 patients received neuraxial anesthesia without any complication and 5 of these 9 patients received prophylactic FFP transfusion. Rest 4 patients had factor level >15%, and neuraxial anesthesia was chosen without any prior FFP transfusion. However, anesthetic options and relevant risks were discussed with patients. 
Salomon et al. described obstetrical outcomes in a series of 62 patients. They found low incidence of hemorrhage despite severe factor XI deficiency and 70% patients had uncomplicated deliveries despite receiving no factor replacement. However, anesthesia techniques were not described. 
A spontaneous epidural hematoma presenting as Brown-Sequard syndrome has been reported in a male with factor XI deficiency, although he made a full recovery subsequently. 
Current evidence on the choice of anesthesia technique in parturient with factor XI deficiency is based on case series and reports only. It is difficult to draw a recommendation in favor of a particular technique. It appears that neuraxial anesthesia may be used in patients with partial factor XI deficiency and following FFP or factor XI transfusion in patients with severe deficiency. However, the consequence of spinal hematoma may make it an unacceptable risk to be taken on the basis of current limited evidence. We chose general anesthesia in our case. Although APTT was made normal by FFP transfusion prior to surgery, considering the facts that the patient had postpartum hemorrhage in a prior pregnancy, history of easy bruisability in the present pregnancy, specific factor transfusion was not given and the factor XI level was not available on the morning of surgery, general anesthesia was preferred over neuraxial blockade. In a review on the management of a pregnant woman with factor XI deficiency, Martín-Salces et al. advised to avoid neuraxial anesthesia in patients with severe factor deficiency with a history of bleeding. 
Neonatal hemorrhage in such cases is rare; however, care should be taken to avoid unnecessary trauma to the baby. Prolonged labor should be avoided, and early recourse to cesarean section should be considered. Vacuum extraction, mid cavity forceps, and forceps involving the rotation of the head should be avoided. Fetal scalp blood sampling and electrode placement should be avoided. 
In conclusion, early involvement of multidisciplinary team consisting of obstetrician, Anesthesiologist and Hematologist, preferring a less traumatic method of delivery, peripartum transfusion of factor XI or FFP to keep a near normal APTT and very careful selection of patients for neuraxial anesthesia with proper risk explanation hold the cornerstones of anesthesia management of parturient with severe factor XI deficiency.
| References|| |
|1.||Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med 1953;82:171-4. |
|2.||Kadir RA, Economides DL, Lee CA. Factor XI deficiency in women. Am J Hematol 1999;60:48-54. |
|3.||O'connell NM. Factor XI deficiency. Semin Hematol 2004;41 Suppl 1:76-81. |
|4.||Salomon O, Seligsohn U. New observations on factor XI deficiency. Haemophilia 2004;10 Suppl 4:184-7. |
|5.||Saunders RE, O'Connell NM, Lee CA, Perry DJ, Perkins SJ. Factor XI deficiency database: An interactive web database of mutations, phenotypes, and structural analysis tools. Hum Mutat 2005;26:192-8. |
|6.||Bolton-Maggs PH, Hill FG. The rarer inherited coagulation disorders: A review. Blood Rev 1995;9:65-76. |
|7.||Lee CA, Chi C, Pavord SR, Bolton-Maggs PH, Pollard D, Hinchcliffe-Wood A, et al. The obstetric and gynaecological management of women with inherited bleeding disorders - Review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors' Organization. Haemophilia 2006;12:301-36. |
|8.||Singh A, Harnett MJ, Connors JM, Camann WR. Factor XI deficiency and obstetrical anesthesia. Anesth Analg 2009;108:1882-5. |
|9.||O'Connell NM, Riddell AF, Pascoe G, Perry DJ, Lee CA. Recombinant factor VIIa to prevent surgical bleeding in factor XI deficiency. Haemophilia 2008;14:775-81. |
|10.||Salomon O, Steinberg DM, Tamarin I, Zivelin A, Seligsohn U. Plasma replacement therapy during labor is not mandatory for women with severe factor XI deficiency. Blood Coagul Fibrinolysis 2005;16:37-41. |
|11.||Mustafa MH, Bernstein RA. Spontaneous spinal epidural hematoma, Brown-Séquard syndrome, and factor XI deficiency. Ann Intern Med 1987;106:477-8. |
|12.||Martín-Salces M, Jimenez-Yuste V, Alvarez MT, Quintana M, Hernández-Navarro F. Review: Factor XI deficiency: Review and management in pregnant women. Clin Appl Thromb Hemost 2010;16:209-13. |