E. Didem ÖZDEMİR, Gamze S. ÇAĞLAR, EFSER ÖZTAŞ, Sevim Dinçer CENGİZ

Herediter trombofili tanısı alan hastalarda aspirin ve düşük molekül ağırlıklı heparin tedavisi ile gebelik sonuçları

Amaç: Herediter trombofililer, kötü gebelik sonuçları ve tromboembolik olaylarla ilişkili bir durumdur. Herediter trombofili gen mutasyonları saptandığında tedavi ile ilgili halen tartışmalar mevcuttur. Bulgular: Bu çalışmada polikliniğimize tekrarlayan gebelik kayıpları, önceki gebeliklerinde tromboz şikayeti ve bebek istemi ile başvuran hastaları ele aldık. Yapılan taramalarda trombofili gen analizinde mutasyonları olan 54 hasta herediter trombofili tanısı aldı. Takipte 42 hastanın 46 gebeliği aspirin ve düşük molekül ağırlıklı heparin tedavisi ile izlendi. Sonuç: Gebelik sonuçlarını retrospektif olarak değerlendirdik. Hastaların tedavi almadıkları önceki gebeliklerine baktığımızda %81 oranında düşük/biyokimyasal abort ve %14 erken doğum, erken membran rüptürü ve preeklampsiye bağlı fetal kayıp mevcuttu. Tedavi sonrası ise %4,3 abortus izlenirken, canlı doğum oranları %95,6 olarak tespit edildi. Tartışma: Bu veriler ışığında heparin ve aspirin tedavisi muhtemel plasental patolojiye bağlı erken gebelik komplikasyonlarını azaltıyor olabilir ancak intrauterin gelişme geriliğinin %25 ve oligohidramniosun %20 oranında tespit edilmesi plasental mikrotrombüslere bağlı tedavi ile önlenemeyen bir patolojiyi akla getirmektedir.

Anahtar Kelimeler:

Gebelik sonucu, Düşük, tekrarlayan, Heparin, düşük molekül ağırlıklı, Gebelik komplikasyonları, Trombofili, Aspirin

Outcome of hereditary thrombophilia managed with salicylic acid and low molecular weight heparin in pregnancy

Objective: Hereditary thrombophilia is associated with adverse pregnancy outcomes and thromboembolic events during pregnancy. There is still controversy on the management and optimal treatment when gene mutations of hereditary thrombophilias are detected. Methods: Patients with a past medical history of more than two pregnancy losses and pregnancies associated with thrombosis are investigated. Fifty four patients were detected to have genetic mutations of thrombophilia. Fourty six pregnancies of 42 patients were followed and managed with salicylic acid and low molecular weight heparin when pregnancy was diagnosed. Results: Pregnancy outcomes of these cases were analyzed. Pregnancies occurring before the diagnosis of the hereditary trombophilias resulted in abortion or biochemical pregnancy in 81% and 14% of these pregnancies were complicated by preterm delivery, preterm premature rupture of membranes or preeclampsia. After the administration of salicylic acid and low molecular weight heparin, only 4,3% of these pregnancies resulted in abortion and the live birth rate was 95,6%. Conclusions: Considering the above results, salicylic acid and low molecular weight heparin therapy might help in early pregnancy complications that might be related with placental pathologies. However, intrauterine growth retardation and oligohydroamnios seen in 25% and 20% of the cases respectively, might indicate placental microthrombosis despite salicylic acid and low molecular weight heparin therapy.

Keywords:

Pregnancy Outcome, Abortion, Habitual, Heparin, Low-Molecular-Weight, Pregnancy Complications, Thrombophilia, Aspirin,

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1. Brenner B. Should thromboprophylaxis be used in hereditary thrombophilias with RPL? in: Ja Carp H, editors. 1st ed. Recurrent Pregnancy Loss Causes, Controversies and Treatment. Taylor&Francis 2007; p: 139-42.
2. Backos M, Regan L. Recurrent Miscarriage. in: James DK, Steer PJ, Weiner CP, Gonik B, editors. 3rd ed. High risk pregnancy. Saunders: Elsevier 2006; p: 105-6.
3. Simpson JL, Jaunıaux ERM. Pregnancy loss. in: Gabbe SG, Niebyl JR, Simpson JL, editors. 5th ed. Obsterics Normal and Problem Pregnancies. Churchill Livingstone: Elsevier 2007; p: 628-49.
4. Inbal A, Ja Carp H. Defects in coagulation factor leading to recurrent pregnancy loss. in: Ja Carp H, editors. 1st ed. Recurrent Pregnancy Loss Causes Controversies and Treatment. Taylor&Francis 2007; p: 127-37.
5. Lindqvist PG. Should thromboprophylaxis be used in hereditary thrombophilias with RPL? Against. in : Ja Carp H, editors. 1st ed. Recurrent Pregnancy Loss Causes, Controversies and Treatment. Taylor&Francis 2007; p: 143-64.
6. Rodger MA, Paidas M, McLintock C, Middeldorp S, Kahn S, Martinelli I, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008;112(2 Pt 1):320-4.
7. Patnaik MM, Haddad T, Morton CT. Pregnancy and thrombophilia. Expert Rev Cardiovasc Ther 2007;5(4):753-65.
8. Xu WH, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, et al. Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 2007;16(2):281-7.
9. Paynter RA, Hankinson SE, Hunter DJ, De Vivo I. No association between MTHFR 677 C->T or 1298 A->C polymorphisms and endometrial cancer risk. Cancer Epidemiol Biomarkers Prev 2004;13(6):1088-9.
10. Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N. Termolabile methylenetetrahydrofolate reductase:an inherited risk factor for coroner artery disease. Am J Hum Genet 1991;48(3):536-45.
11. Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 1992;1;52(7 suppl): 2071s-2077s.
12. Sharp L, Little J. Polymorphism in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 2004 1;159(5):423-43.
13. Gülec S, Aras O, Akar E, Tutar E, Ömürlü K, Avci F, et al. Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction. Clin Cardiol 2001;24(4):281-4.
14. Souza SS, Ferriani RA, Pontes AG, Zago MA, Franco RF. Factor V leiden and factor II G20210A mutations in patients with recurrent abortion. Hum Reprod 1999;14(10):2448-50.
15. Rai R, Backos M, Elgaddal S, Shlebak A, Regan L. Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies. Hum Reprod 2002;17(2):442-5.
16. Ogueh O, Chen MF, Spurli G, Benjamin A. Outcome of pregnancy in women with hereditary thrombophilia. Int J Gynaecol Obstet 2001;74 (3):247-53.
17. Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996;5;348(9032):913-6.
18. Dekker GA, de Vries JI, Doelitzch PM, Huijgens PC, von Blomberg BM, Jakobs C, et al. Underlying disorders associated with severe earlyonset preeclampsia. Am J Obstet Gynecol 1995;173(4):1042-8.
19. Lindoff C, Ingermarsson I, Martinsson G, Segelmark M, Thysell H, Astedt B. Preeclampsia is associated with a reduced response to activated protein C. Am J Obstet Gynecol 1997;176(2):457-60.
20. Facco F, You W, Grobman W. Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstet Gynecol 2009;113 (6):1206-16.
21. Akbaş F, Oral E. Kalıtsal trombofili ve gebelik. Perinatoloji Dergisi 2002;10(1):4-10.
22. Lockwood CJ. Heritable coagulopathies in pregnancy. Obstet Gynecol Surv 1999;54(12):754-65.
23. Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated with enoxaparin. Thromb Haemost 2000;83(5):693-7.
24. Grandone E, Brancaccio V, Colaizzo D, Scianname N, Pavone G, Di Minno G, et al. Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril 2002;78(2):371-75.
25. Kupferminc MJ, Peri H, Zwang E, Yaron Y, Wolman I, Eldor A. High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss. Acta Obstet Gynecol Scand 2000;79(11):963-67.
26. Paidas MJ, Ku DH, Arkel YS. Screening and management of inherited thrombophilias in the setting of adverse pregnancy outcome. Clin Perinatol. 2004;31(4):783-805.
27. Gris JC, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood. 2004 May 15;103(10): 3695-9.
28. Kocher O, Cirovic C, Malynn E, Rowland CM, Bare LA, Young BA, et al. Obstetric complications in patients with hereditary thrombophilia identified using the LCx microparticle enzyme immunoassay: a controlled study of 5,000 patients. Am J Clin Pathol 2007;127(1):68-75.
29. Girling J, de Swiet M. Inherited thrombophilia and pregnancy. Curr Opin Obstet Gynecol 1998;10(2):135-44.
30. Zotz RB, Gerhardt A, Scharf RE. Inherited thrombophilia and gestational venous thromboembolism. Womens Health (Lond Engl) 2007;3 (2):215-25.
31. Dao V, Rodger M. Anticoagulants to prevent placenta-mediated pregnancy complications: a review of current evidence. Curr Opin Hematol 2009;16(5):386-90.