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Hereditary thrombophilia and thromboprophylaxis in pregnancy

Year 2016, Volume: 5 Issue: 1, 83 - 90, 01.01.2016
https://doi.org/10.5505/abantmedj.2016.94803

Abstract

Hereditary Thrombophilia and Thromboprophylaxis in PregnancyObjective: To investigate the effect on maternal venous thromboembolism and negative pregnancy outcomes of widely-used anticoagulant treatments in pregnancies with hereditary thrombophilic defect.Material and Methods: A scan of literature was made using the key words of ‘thrombophilia’, ‘thromboprophylaxis’, ‘anticoagulant treatment’, ‘pregnancy’, and ‘venous thromboembolism’.Results: Thrombophilia is a genetic tendency to arterio-venous thrombotic events, primarily venous and in pregnancy the risk is increased. The causes of hereditary thrombophilia, which is most often seen in pregnancy, are factor V Leiden, prothrombin and methylentetrahydrofolate reductase gene mutations. High risk patients are those with a history of venous thromboemboli, antithrombin deficiency, combined defect, homozygote or combined heterozygote factor V Leiden and prothrombin gene mutations. In these patients, anti-coagulant treatment is indicated in the prevention and treatment of venous thromboembolism. It is a matter of debate as to whether or not there is a causal relationship between thrombophilia and negative outcomes of pregnancy such as recurrent miscarriages, pre-eclampsia, fetal growth restriction and placental abruption. While retrospective, case-control studies have determined a moderate relationship, prospective cohort studies have not provided evidence of this relationship. Conclusion: To determine the effect of thromboprophylaxis applied for hereditary thrombophilia in those with a history of VTE or high risk groups, on negative pregnancy outcomes such as recurrent miscarriages in particular, there is a need for prospective, double-blind randomised studies on larger patient groups with sub-groups of low-risk hereditary thrombophilia.

References

  • 1. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. Journal of thrombosis and haemostasis : JTH. 2005;3(2):292-9.
  • 2. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. The American journal of medicine. 2004;117(1):26-31.
  • 3. Bremme KA. Haemostatic changes in pregnancy. Best practice & research Clinical haematology. 2003;16(2):153-68.
  • 4. Yaşar Z, Talay F. The Management of Thromboembolic Diseases in Pregnancy. Abant Medical Journal. 2015;4(3):302-8.
  • 5. Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstetrics and gynecology. 1999;94(5 Pt 1):730-4.
  • 6. Weintraub AY, Sheiner E. Anticoagulant therapy and thromboprophylaxis in patients with thrombophilia. Archives of gynecology and obstetrics. 2007;276(6):567-71.
  • 7. Lussana F, Coppens M, Cattaneo M, Middeldorp S. Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis. Thrombosis research. 2012;129(6):673-80.
  • 8. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010;376(9751):1498-509.
  • 9. Sanson BJ, Friederich PW, Simioni P, Zanardi S, Hilsman MV, Girolami A, et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein Sdeficient women. Thrombosis and haemostasis. 1996;75(3):387-8.
  • 10. Said JM, Higgins JR, Moses EK, Walker SP, Borg AJ, Monagle PT, et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstetrics and gynecology. 2010;115(1):5-13.
  • 11. Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J, Investigators L-E. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVEENOX study. Journal of thrombosis and haemostasis : JTH. 2005;3(2):227-9.
  • 12. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-8.
  • 13. Vossen CY, Preston FE, Conard J, Fontcuberta J, Makris M, van der Meer FJ, et al. Hereditary thrombophilia and fetal loss: a prospective follow-up study. Journal of thrombosis and haemostasis : JTH. 2004;2(4):592-6.
  • 14. Laskin CA, Spitzer KA, Clark CA, Crowther MR, Ginsberg JS, Hawker GA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. The Journal of rheumatology. 2009;36(2):279-87.
  • 15. Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyak K, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. The New England journal of medicine. 2010;362(17):1586-96.
  • 16. Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood. 2010;115(21):4162-7.
  • 17. Visser J, Ulander VM, Helmerhorst FM, Lampinen K, Morin-Papunen L, Bloemenkamp KW, et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial. Thrombosis and haemostasis. 2011;105(2):295-301.
  • 18. Facco F, You W, Grobman W. Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstetrics and gynecology. 2009;113(6):1206-16.
  • 19. American College of O, Gynecologists Women's Health Care P. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstetrics and gynecology. 2013;122(3):706-17.
  • 20. Haemostasis, Thrombosis Task Force BCfSiH. Investigation and management of heritable thrombophilia. British journal of haematology. 2001;114(3):512-28.
  • 21. Zotz RB, Gerhardt A, Scharf RE. Inherited thrombophilia and gestational venous thromboembolism. Best practice & research Clinical haematology. 2003;16(2):243-59.
  • 22. Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. The New England journal of medicine. 2008;359(19):2025-33.
  • 23. Coppola A, Tufano A, Cerbone AM, Di Minno G. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism. Seminars in thrombosis and hemostasis. 2009;35(7):683-94.
  • 24. Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1995;108(4 Suppl):258S-75S.
  • 25. Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. American journal of obstetrics and gynecology. 1965;93(4):570-3.
  • 26. Pettila V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thrombosis and haemostasis. 2002;87(2):182-6.
  • 27. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al. Heparin-induced thrombocytopenia in patients treated with low-molecularweight heparin or unfractionated heparin. The New England journal of medicine. 1995;332(20):1330-5.
  • 28. Woo YL, Allard S, Cohen H, Letsky E, de Swiet M. Danaparoid thromboprophylaxis in pregnant women with heparin-induced thrombocytopenia. BJOG : an international journal of obstetrics and gynaecology. 2002;109(4):466-8.
  • 29. Huhle G, Geberth M, Hoffmann U, Heene DL, Harenberg J. Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin. Gynecologic and obstetric investigation. 2000;49(1):67-9.
  • 30. Holst J, Lindblad B, Bergqvist D, Garre K, Nielsen H, Hedner U, et al. Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 1994;5(5):795-803.
  • 31. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Archives of internal medicine. 2000;160(2):191-6.
  • 32. Panduranga P, El-Deeb M, Jha C. Mechanical Prosthetic Valves and Pregnancy: A therapeutic dilemma of anticoagulation. Sultan Qaboos University medical journal. 2014;14(4):e448-54.
  • 33. Geelani MA, Singh S, Verma A, Nagesh A, Betigeri V, Nigam M. Anticoagulation in patients with mechanical valves during pregnancy. Asian cardiovascular & thoracic annals. 2005;13(1):30-3.

Gebelikte kalıtsal trombofili ve tromboprofilaksi

Year 2016, Volume: 5 Issue: 1, 83 - 90, 01.01.2016
https://doi.org/10.5505/abantmedj.2016.94803

Abstract

Gebelikte Kalıtsal Trombofili ve TromboprofilaksiAmaç: Kalıtsal trombofilik defekti olan gebelerde yaygın olarak kullanılan antikoagulan tedavilerin maternal venöz tromboembolizm ve olumsuz gebelik sonuçlarına etkisini araştırmaktır.Gereç ve Yöntemler: “Kalıtsal trombofili”, “tromboprofilaksi”, “antikoagulan tedavi”, “gebelik”, “venöz tromboembolizm” anahtar kelimeleri ile literatür taraması yapıldı.Bulgular: Trombofili daha çok venöz olmak üzere arterio venöz trombotik olaylara genetik yatkınlık olmasıdır ve gebelikte risk artar. Gebelikte en sık görülen kalıtsal trombofili nedenleri faktör V Leiden, protrombin ve metilentetrahidrofolat redüktaz gen mutasyonlarıdır. Geçirilmiş venöz tromboemboli öyküsü, antitrombin eksikliği, kombine defekt, homozigot veya birleşik heterozigot faktör V Leiden ve protrombin gen mutasyonları olanlar yüksek riskli hastalardır. Bu hastalarda, antikoagulan tedavi venöz tromboembolizmin önlenmesinde ve tedavisinde endikedir. Trombofili ile tekrarlayan gebelik kaybı, preeklampsi, fetal büyüme kısıtlılığı ve ablasyo plasenta gibi olumsuz gebelik sonuçları arasında nedensel bir ilişki olup olmadığı tartışmalıdır. Retrospektif, vaka-kontrol çalışmalar ılımlı bir ilişki ortaya koyar iken, prospektif kohort çalışmalar ile bu ilişki kanıtlanmamıştır. Sonuç: Kalıtsal trombofilide, VTE öyküsü olanlarda ve yüksek riskli gruplarda uygulanan tromboprofilaksinin özellikle tekrarlayan gebelik kayıpları gibi olumsuz gebelik sonuçlarına etkisini ortaya koymak için kalıtsal trombofilinin düşük riskli subgruplarına yönelik daha geniş hasta gruplarında, prospektif, çift-kör, randomize çalışmalara ihtiyaç vardır.

References

  • 1. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. Journal of thrombosis and haemostasis : JTH. 2005;3(2):292-9.
  • 2. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. The American journal of medicine. 2004;117(1):26-31.
  • 3. Bremme KA. Haemostatic changes in pregnancy. Best practice & research Clinical haematology. 2003;16(2):153-68.
  • 4. Yaşar Z, Talay F. The Management of Thromboembolic Diseases in Pregnancy. Abant Medical Journal. 2015;4(3):302-8.
  • 5. Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstetrics and gynecology. 1999;94(5 Pt 1):730-4.
  • 6. Weintraub AY, Sheiner E. Anticoagulant therapy and thromboprophylaxis in patients with thrombophilia. Archives of gynecology and obstetrics. 2007;276(6):567-71.
  • 7. Lussana F, Coppens M, Cattaneo M, Middeldorp S. Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis. Thrombosis research. 2012;129(6):673-80.
  • 8. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010;376(9751):1498-509.
  • 9. Sanson BJ, Friederich PW, Simioni P, Zanardi S, Hilsman MV, Girolami A, et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein Sdeficient women. Thrombosis and haemostasis. 1996;75(3):387-8.
  • 10. Said JM, Higgins JR, Moses EK, Walker SP, Borg AJ, Monagle PT, et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstetrics and gynecology. 2010;115(1):5-13.
  • 11. Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J, Investigators L-E. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVEENOX study. Journal of thrombosis and haemostasis : JTH. 2005;3(2):227-9.
  • 12. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-8.
  • 13. Vossen CY, Preston FE, Conard J, Fontcuberta J, Makris M, van der Meer FJ, et al. Hereditary thrombophilia and fetal loss: a prospective follow-up study. Journal of thrombosis and haemostasis : JTH. 2004;2(4):592-6.
  • 14. Laskin CA, Spitzer KA, Clark CA, Crowther MR, Ginsberg JS, Hawker GA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. The Journal of rheumatology. 2009;36(2):279-87.
  • 15. Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyak K, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. The New England journal of medicine. 2010;362(17):1586-96.
  • 16. Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood. 2010;115(21):4162-7.
  • 17. Visser J, Ulander VM, Helmerhorst FM, Lampinen K, Morin-Papunen L, Bloemenkamp KW, et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial. Thrombosis and haemostasis. 2011;105(2):295-301.
  • 18. Facco F, You W, Grobman W. Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstetrics and gynecology. 2009;113(6):1206-16.
  • 19. American College of O, Gynecologists Women's Health Care P. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstetrics and gynecology. 2013;122(3):706-17.
  • 20. Haemostasis, Thrombosis Task Force BCfSiH. Investigation and management of heritable thrombophilia. British journal of haematology. 2001;114(3):512-28.
  • 21. Zotz RB, Gerhardt A, Scharf RE. Inherited thrombophilia and gestational venous thromboembolism. Best practice & research Clinical haematology. 2003;16(2):243-59.
  • 22. Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. The New England journal of medicine. 2008;359(19):2025-33.
  • 23. Coppola A, Tufano A, Cerbone AM, Di Minno G. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism. Seminars in thrombosis and hemostasis. 2009;35(7):683-94.
  • 24. Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1995;108(4 Suppl):258S-75S.
  • 25. Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. American journal of obstetrics and gynecology. 1965;93(4):570-3.
  • 26. Pettila V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thrombosis and haemostasis. 2002;87(2):182-6.
  • 27. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al. Heparin-induced thrombocytopenia in patients treated with low-molecularweight heparin or unfractionated heparin. The New England journal of medicine. 1995;332(20):1330-5.
  • 28. Woo YL, Allard S, Cohen H, Letsky E, de Swiet M. Danaparoid thromboprophylaxis in pregnant women with heparin-induced thrombocytopenia. BJOG : an international journal of obstetrics and gynaecology. 2002;109(4):466-8.
  • 29. Huhle G, Geberth M, Hoffmann U, Heene DL, Harenberg J. Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin. Gynecologic and obstetric investigation. 2000;49(1):67-9.
  • 30. Holst J, Lindblad B, Bergqvist D, Garre K, Nielsen H, Hedner U, et al. Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 1994;5(5):795-803.
  • 31. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Archives of internal medicine. 2000;160(2):191-6.
  • 32. Panduranga P, El-Deeb M, Jha C. Mechanical Prosthetic Valves and Pregnancy: A therapeutic dilemma of anticoagulation. Sultan Qaboos University medical journal. 2014;14(4):e448-54.
  • 33. Geelani MA, Singh S, Verma A, Nagesh A, Betigeri V, Nigam M. Anticoagulation in patients with mechanical valves during pregnancy. Asian cardiovascular & thoracic annals. 2005;13(1):30-3.
There are 33 citations in total.

Details

Primary Language English
Journal Section Collection
Authors

Hüsnü Alptekin This is me

Şeref Ulucan This is me

Türkan Cengiz This is me

Refika Selimoğlu This is me

Publication Date January 1, 2016
Published in Issue Year 2016 Volume: 5 Issue: 1

Cite

APA Alptekin, H., Ulucan, Ş., Cengiz, T., Selimoğlu, R. (2016). Hereditary thrombophilia and thromboprophylaxis in pregnancy. Abant Medical Journal, 5(1), 83-90. https://doi.org/10.5505/abantmedj.2016.94803
AMA Alptekin H, Ulucan Ş, Cengiz T, Selimoğlu R. Hereditary thrombophilia and thromboprophylaxis in pregnancy. Abant Med J. January 2016;5(1):83-90. doi:10.5505/abantmedj.2016.94803
Chicago Alptekin, Hüsnü, Şeref Ulucan, Türkan Cengiz, and Refika Selimoğlu. “Hereditary Thrombophilia and Thromboprophylaxis in Pregnancy”. Abant Medical Journal 5, no. 1 (January 2016): 83-90. https://doi.org/10.5505/abantmedj.2016.94803.
EndNote Alptekin H, Ulucan Ş, Cengiz T, Selimoğlu R (January 1, 2016) Hereditary thrombophilia and thromboprophylaxis in pregnancy. Abant Medical Journal 5 1 83–90.
IEEE H. Alptekin, Ş. Ulucan, T. Cengiz, and R. Selimoğlu, “Hereditary thrombophilia and thromboprophylaxis in pregnancy”, Abant Med J, vol. 5, no. 1, pp. 83–90, 2016, doi: 10.5505/abantmedj.2016.94803.
ISNAD Alptekin, Hüsnü et al. “Hereditary Thrombophilia and Thromboprophylaxis in Pregnancy”. Abant Medical Journal 5/1 (January 2016), 83-90. https://doi.org/10.5505/abantmedj.2016.94803.
JAMA Alptekin H, Ulucan Ş, Cengiz T, Selimoğlu R. Hereditary thrombophilia and thromboprophylaxis in pregnancy. Abant Med J. 2016;5:83–90.
MLA Alptekin, Hüsnü et al. “Hereditary Thrombophilia and Thromboprophylaxis in Pregnancy”. Abant Medical Journal, vol. 5, no. 1, 2016, pp. 83-90, doi:10.5505/abantmedj.2016.94803.
Vancouver Alptekin H, Ulucan Ş, Cengiz T, Selimoğlu R. Hereditary thrombophilia and thromboprophylaxis in pregnancy. Abant Med J. 2016;5(1):83-90.