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Semin Thromb Hemost 2016; 42(07): 732-740
DOI: 10.1055/s-0036-1587685
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Management of Factor XI Deficiency in Pregnancy

Joanna Davies
1   Department of Obstetrics and Gynaecology, The Royal Free Hospital, London, United Kingdom
,
Rezan Kadir
1   Department of Obstetrics and Gynaecology, The Royal Free Hospital, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
03 October 2016 (online)

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Abstract

Management of factor XI (FXI) deficiency in pregnancy is complicated by lack of correlation between FXI level and bleeding risk. Clinicians should be vigilant about the potential for prolonged or excessive bleeding following miscarriage or termination of pregnancy, or postpartum hemorrhage (PPH). A multidisciplinary approach along with an individual care plan is recommended to prevent bleeding complications. Assessment of bleeding history, FXI level, and global tests of hemostasis can aid management decisions regarding hemostatic prophylaxis. The risk of PPH can be minimized by obstetric measures to avoid uterine atony and genital trauma, in addition to provision of appropriate hemostatic prophylaxis for labor and delivery. Women with FXI deficiency can be given the option of regional anesthesia, provided that prior consideration has been given to assessment of potential bleeding risk and appropriate treatment strategies are implemented. Antifibrinolytic agents are effective for the majority of women with FXI deficiency, but those with severe deficiency/phenotype require FXI concentrate. Recombinant activated factor VII (rFVIIa) has also been used successfully to prevent bleeding in FXI deficiency. However, all treatments should be used with caution in pregnancy due to thrombogenic potential. Neonatal bleeding complications are rare in FXI deficiency; however, hemostatic assessment and cover are important for invasive procedures such as circumcision.

Keywords

factor XI deficiency - pregnancy - delivery
 

  • References

  • 1 Seligsohn U. High gene frequency of factor XI (PTA) deficiency in Ashkenazi Jews. Blood 1978; 51 (6) 1223-1228
    PubMedGoogle Scholar
  • 2 Kadir RA, Kingman CE, Chi C , et al. Screening for factor XI deficiency amongst pregnant women of Ashkenazi Jewish origin. Haemophilia 2006; 12 (6) 625-628
    CrossrefPubMedGoogle Scholar
  • 3 Bolton-Maggs PH. Bleeding problems in factor XI deficient women. Haemophilia 1999; 5 (3) 155-159
    CrossrefPubMedGoogle Scholar
  • 4 Rapaport SI, Proctor RR, Patch MJ, Yettra M. The mode of inheritance of PTA deficiency: evidence for the existence of major PTA deficiency and minor PTA deficiency. Blood 1961; 18: 149-165
    PubMedGoogle Scholar
  • 5 Leiba H, Ramot B, Many A. Heredity and coagulation studies in ten families with Factor XI (plasma thromboplastin antecedent) deficiency. Br J Haematol 1965; 11 (6) 654-665
    CrossrefPubMedGoogle Scholar
  • 6 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 (3) 192-198
    CrossrefPubMedGoogle Scholar
  • 7 Ragni MV, Sinha D, Seaman F, Lewis JH, Spero JA, Walsh PN. Comparison of bleeding tendency, factor XI coagulant activity, and factor XI antigen in 25 factor XI-deficient kindreds. Blood 1985; 65 (3) 719-724
    PubMedGoogle Scholar
  • 8 Bolton-Maggs PH, Patterson DA, Wensley RT, Tuddenham EG. Definition of the bleeding tendency in factor XI-deficient kindreds—a clinical and laboratory study. Thromb Haemost 1995; 73 (2) 194-202
    PubMedGoogle Scholar
  • 9 Peyvandi F, Palla R, Menegatti M , et al; European Network of Rare Bleeding Disorders Group. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10 (4) 615-621
    CrossrefPubMedGoogle Scholar
  • 10 Santoro C, Di Mauro R, Baldacci E , et al. Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre. Haemophilia 2015; 21 (4) 496-501
    CrossrefPubMedGoogle Scholar
  • 11 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 (1) 37-41
    CrossrefPubMedGoogle Scholar
  • 12 Brenner B, Laor A, Lupo H, Zivelin A, Lanir N, Seligsohn U. Bleeding predictors in factor-XI-deficient patients. Blood Coagul Fibrinolysis 1997; 8 (8) 511-515
    CrossrefPubMedGoogle Scholar
  • 13 Peyvandi F, Lak M, Mannucci PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica 2002; 87 (5) 512-514
    PubMedGoogle Scholar
  • 14 Guéguen P, Galinat H, Blouch MT , et al. Biological determinants of bleeding in patients with heterozygous factor XI deficiency. Br J Haematol 2012; 156 (2) 245-251
    CrossrefPubMedGoogle Scholar
  • 15 Rugeri L, Quélin F, Chatard B, De Mazancourt P, Negrier C, Dargaud Y. Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia 2010; 16 (5) 771-777
    CrossrefPubMedGoogle Scholar
  • 16 Zucker M, Seligsohn U, Salomon O, Wolberg AS. Abnormal plasma clot structure and stability distinguish bleeding risk in patients with severe factor XI deficiency. J Thromb Haemost 2014; 12 (7) 1121-1130
    CrossrefPubMedGoogle Scholar
  • 17 Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiency in Ashkenazi Jews in Israel. N Engl J Med 1991; 325 (3) 153-158
    CrossrefPubMedGoogle Scholar
  • 18 Bolton-Maggs PH, Young Wan-Yin B, McCraw AH, Slack J, Kernoff PB. Inheritance and bleeding in factor XI deficiency. Br J Haematol 1988; 69 (4) 521-528
    CrossrefPubMedGoogle Scholar
  • 19 Zivelin A, Bauduer F, Ducout L , et al. Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene. Blood 2002; 99 (7) 2448-2454
    CrossrefPubMedGoogle Scholar
  • 20 Livnat T, Shenkman B, Martinowitz U , et al. The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency. Thromb Res 2015; 136 (2) 465-473
    CrossrefPubMedGoogle Scholar
  • 21 Davies J, Harper A, Kadir RA. The role of rotational thromboelastometry in assessment of haemostasis during pregnancy in women with factor XI deficiency. Haemophilia 2015;
    PubMedGoogle Scholar
  • 22 Hellgren M, Blombäck M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest 1981; 12 (3) 141-154
    CrossrefPubMedGoogle Scholar
  • 23 Beller FK, Ebert C. The coagulation and fibrinolytic enzyme system in pregnancy and in the puerperium. Eur J Obstet Gynecol Reprod Biol 1982; 13 (3) 177-197
    CrossrefPubMedGoogle Scholar
  • 24 Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52 (2) 176-182
    PubMedGoogle Scholar
  • 25 Kruithof EK, Tran-Thang C, Gudinchet A , et al. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood 1987; 69 (2) 460-466
    PubMedGoogle Scholar
  • 26 Clark P. Changes of hemostasis variables during pregnancy. Semin Vasc Med 2003; 3 (1) 13-24
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Chi C, Kulkarni A, Lee CA, Kadir RA. The obstetric experience of women with factor XI deficiency. Acta Obstet Gynecol Scand 2009; 88 (10) 1095-1100
    CrossrefPubMedGoogle Scholar
  • 28 Myers B, Pavord S, Kean L, Hill M, Dolan G. Pregnancy outcome in Factor XI deficiency: incidence of miscarriage, antenatal and postnatal haemorrhage in 33 women with Factor XI deficiency. BJOG 2007; 114 (5) 643-646
    CrossrefPubMedGoogle Scholar
  • 29 Kadir RA, Lee CA, Sabin CA, Pollard D, Economides DL. Pregnancy in women with von Willebrand's disease or factor XI deficiency. Br J Obstet Gynaecol 1998; 105 (3) 314-321
    CrossrefPubMedGoogle Scholar
  • 30 Myers B, Neal R, Curry N, Kadir RA, Pavord S. Abstracts of the XXV Congress of the International Society on Thrombosis and Haemostasis, June 20-25, 2015. J Thromb Haemost 2015; 13 (Suppl. 02) 1-997
    PubMedGoogle Scholar
  • 31 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69 (6) 1691-1695
    CrossrefPubMedGoogle Scholar
  • 32 Yan J, Saravelos SH, Ma N, Ma C, Chen ZJ, Li TC. Consecutive repeat miscarriages are likely to occur in the same gestational period. Reprod Biomed Online 2012; 24 (6) 634-638
    CrossrefPubMedGoogle Scholar
  • 33 Sinha P, Kuruba N. Ante-partum haemorrhage: an update. J Obstet Gynaecol 2008; 28 (4) 377-381
    CrossrefPubMedGoogle Scholar
  • 34 Jadon A. Complications of regional and general anaesthesia in obstetric practice. Indian J Anaesth 2010; 54 (5) 415-420
    CrossrefPubMedGoogle Scholar
  • 35 Ruppen W, Derry S, McQuay H, Moore RA. Incidence of epidural hematoma, infection, and neurologic injury in obstetric patients with epidural analgesia/anesthesia. Anesthesiology 2006; 105 (2) 394-399
    CrossrefPubMedGoogle Scholar
  • 36 Chi C, Lee CA, England A, Hingorani J, Paintsil J, Kadir RA. Obstetric analgesia and anaesthesia in women with inherited bleeding disorders. Thromb Haemost 2009; 101 (6) 1104-1111
    PubMedGoogle Scholar
  • 37 Singh A, Harnett MJ, Connors JM, Camann WR. Factor XI deficiency and obstetrical anesthesia. Anesth Analg 2009; 108 (6) 1882-1885
    CrossrefPubMedGoogle Scholar
  • 38 El-Refaey H, Rodeck C. Post-partum haemorrhage: definitions, medical and surgical management. A time for change. Br Med Bull 2003; 67: 205-217
    CrossrefPubMedGoogle Scholar
  • 39 Hoveyda F, MacKenzie IZ. Secondary postpartum haemorrhage: incidence, morbidity and current management. BJOG 2001; 108 (9) 927-930
    PubMedGoogle Scholar
  • 40 Chi C, Bapir M, Lee CA, Kadir RA. Puerperal loss (lochia) in women with or without inherited bleeding disorders. Am J Obstet Gynecol 2010; 203 (1) 56.e1-56.e5
    CrossrefPubMedGoogle Scholar
  • 41 Huq FY, Kulkarni A, Agbim EC, Riddell A, Tuddenham E, Kadir RA. Changes in the levels of factor VIII and von Willebrand factor in the puerperium. Haemophilia 2012; 18 (2) 241-245
    CrossrefPubMedGoogle Scholar
  • 42 James AH, Konkle BA, Kouides P , et al. Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis. Haemophilia 2015; 21 (1) 81-87
    CrossrefPubMedGoogle Scholar
  • 43 Saha P, Stott D, Atalla R. Haemostatic changes in the puerperium ‘6 weeks postpartum’ (HIP Study) - implication for maternal thromboembolism. BJOG 2009; 116 (12) 1602-1612
    CrossrefPubMedGoogle Scholar
  • 44 Andrew M, Paes B, Milner R , et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (1) 165-172
    PubMedGoogle Scholar
  • 45 Chalmers EA. Neonatal coagulation problems. Arch Dis Child Fetal Neonatal Ed 2004; 89 (6) F475-F478
    CrossrefPubMedGoogle Scholar
  • 46 Bolton-Maggs PH. Factor XI deficiency and its management. Haemophilia 2000; 6 (Suppl. 01) 100-109
    CrossrefPubMedGoogle Scholar
  • 47 Collins PW, Goldman E, Lilley P, Pasi KJ, Lee CA. Clinical experience of factor XI deficiency: the role of fresh frozen plasma and factor XI concentrate. Haemophilia 1995; 1 (4) 227-231
    CrossrefPubMedGoogle Scholar
  • 48 Wiewel-Verschueren S, Arendz IJ, M. Knol H, Meijer K. Gynaecological and obstetrical bleeding in women with factor XI deficiency - a systematic review. Haemophilia 2015;
    PubMedGoogle Scholar
  • 49 Lee CA, Chi C, Pavord SR , et al; UK Haemophilia Centre Doctors' Organization. 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 (4) 301-336
    CrossrefPubMedGoogle Scholar
  • 50 O'Brien P, El-Refaey H, Gordon A, Geary M, Rodeck CH. Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study. Obstet Gynecol 1998; 92 (2) 212-214
    PubMedGoogle Scholar
  • 51 Gomez K, Bolton-Maggs P. Factor XI deficiency. Haemophilia 2008; 14 (6) 1183-1189
    PubMedGoogle Scholar
  • 52 Ducloy-Bouthors AS, Jude B, Duhamel A , et al; EXADELI Study Group. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 2011; 15 (2) R117
    CrossrefPubMedGoogle Scholar
  • 53 Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynaecol Obstet 2011; 115 (3) 224-226
    CrossrefPubMedGoogle Scholar
  • 54 Gungorduk K, Yıldırım G, Asıcıoğlu O, Gungorduk OC, Sudolmus S, Ark C. Efficacy of intravenous tranexamic acid in reducing blood loss after elective cesarean section: a prospective, randomized, double-blind, placebo-controlled study. Am J Perinatol 2011; 28 (3) 233-240
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Peitsidis P, Kadir RA. Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother 2011; 12 (4) 503-516
    CrossrefPubMedGoogle Scholar
  • 56 Gerbasi FR, Bottoms S, Farag A, Mammen E. Increased intravascular coagulation associated with pregnancy. Obstet Gynecol 1990; 75 (3, Pt 1): 385-389
    PubMedGoogle Scholar
  • 57 Ferrer P, Roberts I, Sydenham E, Blackhall K, Shakur H. Anti-fibrinolytic agents in post partum haemorrhage: a systematic review. BMC Pregnancy Childbirth 2009; 9: 29
    CrossrefPubMedGoogle Scholar
  • 58 Shakur H, Elbourne D, Gülmezoglu M , et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 2010; 11: 40
    CrossrefPubMedGoogle Scholar
  • 59 Bolton-Maggs PH. Factor XI deficiency—resolving the enigma?. Hematology Am Soc Hematol Educ Program 2009; 97-105
    PubMedGoogle Scholar
  • 60 Bolton-Maggs PH, Colvin BT, Satchi BT, Lee CA, Lucas GS. Thrombogenic potential of factor XI concentrate. Lancet 1994; 344 (8924) 748-749
    PubMedGoogle Scholar
  • 61 Hoffman C, Hultin MB. Factor IX concentrate therapy and thrombosis: relation to changes in plasma antithrombin III. Thromb Res 1986; 43 (2) 143-151
    CrossrefPubMedGoogle Scholar
  • 62 Keeling D, Tait C, Makris M. Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. A United Kingdom Haemophilia Center Doctors' Organisation (UKHCDO) guideline approved by the British Committee for Standards in Haematology. Haemophilia 2008; 14 (4) 671-684
    CrossrefPubMedGoogle Scholar
  • 63 Lindgren L, Yli-Hankala A, Halme L, Koskimies S, Orko R. Transfusion-related acute lung injury (TRALI) after fresh frozen plasma in a patient with coagulopathy. Acta Anaesthesiol Scand 1996; 40 (5) 641-644
    CrossrefPubMedGoogle Scholar
  • 64 Salomon O, Zivelin A, Livnat T , et al. Prevalence, causes, and characterization of factor XI inhibitors in patients with inherited factor XI deficiency. Blood 2003; 101 (12) 4783-4788
    CrossrefPubMedGoogle Scholar
  • 65 Kenet G, Lubetsky A, Luboshitz J , et al. Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors. Haemophilia 2009; 15 (5) 1065-1073
    CrossrefPubMedGoogle Scholar
  • 66 Livnat T, Tamarin I, Mor Y , et al. Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies. Thromb Haemost 2009; 102 (3) 487-492
    PubMedGoogle Scholar
  • 67 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 (4) 775-781
    CrossrefPubMedGoogle Scholar
  • 68 Riddell A, Abdul-Kadir R, Pollard D, Tuddenham E, Gomez K. Monitoring low dose recombinant factor VIIa therapy in patients with severe factor XI deficiency undergoing surgery. Thromb Haemost 2011; 106 (3) 521-527
    Article in Thieme ConnectPubMedGoogle Scholar
  • 69 Mumford AD, Ackroyd S, Alikhan R , et al; BCSH Committee. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol 2014; 167 (3) 304-326
    CrossrefPubMedGoogle Scholar