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DOI: 10.1055/s-0037-1613894
Gestational Outcome in Thrombophilic Women with Recurrent Pregnancy Loss Treated by Enoxaparin
Publication History
Received
07 October 1999
Accepted after revision
05 January 2000
Publication Date:
08 December 2017 (online)
Summary
Inherited and acquired thrombophilia are associated with recurrent pregnancy loss (RPL). We have evaluated the efficacy and safety of the low molecular weight heparin enoxaparin in 50 women, (mean age 26 ± 3 years) with RPL (>3 losses in 1st, >2 losses in 2nd and >1 loss in 3rd trimester) who were found to harbor thrombophilia. Twentyseven had a solitary thrombophilic defect, and twenty-three women had combined thrombophilic defects: 17 – two defects and 6 – three defects. Following diagnosis of thrombophilia, sixty-one subsequent pregnancies were treated with the low molecular weight heparin enoxaparin throughout gestation until 4 weeks after delivery. Dosage was 40 mg/day in women with solitary defect and 80 mg/day in combined defects. Aspirin, 75 mg daily was given in addition to enoxaparin to women with antiphospholipid syndrome. Forty-six out of 61 (75%) gestations treated by enoxaparin resulted in live birth compared to only 38/193 (20%) of the untreated pregnancies in these 50 women prior to diagnosis of thrombophilia (p <0.00001). In 23 women without a single living child following 82 untreated gestations, antithrombotic therapy resulted in 26/31 (84%) successful deliveries (p <0.0001). In 20 women with a prior living child, antithrombotic therapy improved successful delivery from 33/86 (38%) to 20/21 (95%) (p <0.0001). Enoxaparin dose of 40 mg/day resulted in live birth in 24/35 (69%) of gestations, compared to 19/23 (83%) gestations in women treated with 80 mg/day (p = 0.37). Only one thrombotic episode and one mildbleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.
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References
- 1 Clifford K, Rai R, Wason H, Regan L. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Human Reprod 1994; 09: 1328-32.
- 2 Hatasaka HH. Recurrent miscarriage: epidemiologic factors, definitions, and incidence. Clin Obstet Gynecol 1994; 37: 625-34.
- 3 Triplett DA, Harris EN. Antiphospholipid antibodies and reproduction. Am J Reprod Immunol 1989; 21: 123-31.
- 4 Brenner B. Inherited thrombophilia and pregnancy loss. Thromb Haemost 1999; 82 (02) 634-40.
- 5 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia Report on a study of the SSC Subcommittee of Fibrinogen. Thromb Haemost 1995; 73: 151-61.
- 6 Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, Fontcuberta J, Makris M, Mariani G, Noteboom W, Pabinger I, Legnani C, Scharrer I, Schulman S, van der Meer FJ. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-6.
- 7 Rai R, Regan L, Hadley E, Dave M, Cohen H. Second trimester pregnancy loss is associated with activated protein C resistance. Br J Haematol 1996; 92: 489-90.
- 8 Grandone E, Margaglione M, Colaizzo D, d’Addedda M, Cappucci G, Vecchione G, Scianname N, Pavone G, Di Minno G. Factor V Leiden is associated with repeated and recurrent unexplained fetal losses. Thromb Haemost 1997; 77: 822-4.
- 9 Ridker PM, Miletich JP, Buring JE, Ariyo AA, Price DT, Manson JE, Hill JA. Factor V Leiden mutation as a risk factor for recurrent pregnancy loss. Ann Intern Med 1998; 128: 1000-3.
- 10 Brenner B, Sarig G, Weiner Z, Younis J, Blumenfeld Z, Lanir N. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost 1999; 82: 6-9.
- 11 Nelen WL, Blom HJ, Thomas CM, Steegers EA, Boers CH, Eskes TK. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr 1998; 128: 1336-41.
- 12 Deitcher SR, Park VM, Kuteh WH. Prothrombin 20210G > A mutation analysis in Caucasian women with early first trimester recurrent pregnancy loss. Blood. 1998 92. (suppl 01) 118b (Abstr).
- 13 Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Fait G, Lessing JB. Increased frequency of genetic thrombophilias in women with complications of pregnancy. N Engl J Med 1999; 340: 9-13.
- 14 Brenner B, Mandel H, Lanir N, Younis J, Rothbart H, Ohel G, Blumenfeld Z. Activated protein C resistance can be associated with recurrent fetal loss. Br J Haematol 1997; 97: 551-4.
- 15 Goddijn-Wessel TA, Wouters MG, van der Molen EF, Spuijbrock MD, Steegers-Theunissen RP, Blom HJ, Boers GH, Eskes TK. Hyper-homocysteinemia: a risk factor for placental abruption or infarction. Eur J Obstet Gynecol Rep Biol 1996; 66: 23-9.
- 16 Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 1996; 174: 1584-9.
- 17 Rai R, Cohen H, Dave M, Regan L. Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with antiphospholipid antibodies. Br Med J 1997; 314: 253-7.
- 18 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulant. Blood 1986; 68: 869-74.
- 19 Exner T. Diagnostic methodologies for circulating anticoagulants. Thromb Haemost 1995; 74: 338-44.
- 20 Mandel H, Brenner B, Berant M, Rosenberg N, Lanir N, Jakobs C, Fowler B, Seligsohn U. Coexistence of hereditary homocysteinuria and factor V Leiden – effect on thrombosis. N Engl J Med 1996; 334: 763-8.
- 21 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
- 22 De Franchis R, Mancini FP, D’Angelo A, Sebastio G, Fermo I, De Stefano V, Margaglione M, Mazzalo G, Di Minno G, Andria G. Elevated total plasma homocysteine and C→T mutation of 5,10 methylenetetrahydro-folate reductase gene in thrombotic vascular disease. Am J Hum Genet 1996; 59: 262-4.
- 23 Sarig G, Hoffman R, Younis J, Lanir N, Blumenfeld Z, Brenner B. Thrombophilia is common in women with pregnancy loss and is associated with late pregnancy wastage. Thromb Haemost. 1999 226. (Suppl.): (abstr).
- 24 Infante-Rivard C, David M, Gauthier R, Riverd GE. Lupus anticoagulants, anticardiolipin antibodies and fetal loss. N Engl J Med 1991; 325: 1063-6.
- 25 Brenner B, Zivelin A, Lanir N, Greengard JS, Griffin JH, Seligsohn U. Venous thrombo-embolism associated with double heterozygosity for R506Q mutation of factor V and for T298M mutation of protein C in a large family of a previously described homozygous protein C deficient newborn with massive thrombosis. Blood 1996; 88: 877-88.
- 26 Salomon O, Steinberg DM, Zivelin A, Gitel S, Dardik R, Rosenberg N, Berliner S, Inbal A, Many A, Lubetsky A, Varon D, Martinowitz U, Seligsohn U. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism, prevalence and risk assessment. Arterioscler Thromb Vasc Biol 1999; 19: 511-8.
- 27 Sanson BJ, Lensing AWA, Prins MH, Ginsberg JS, Barkagan ZS, Labenne-Pardonge E, Brenner B, Duitzky M, Nielsen JD, Boda Z, Turi S, Mac MRGillavry, Hamulyak K, Theunissen IM, Hunt BJ, Büller HR. Safety of low-molecular-weight heparin in pregnancy: A systematic review. Thromb Haemost 1999; 81: 668-72.
- 28 Gris JC, Neveu S, Tailland ML, Courtieu C, Mares P, Schved JF. Use of low-molecular weight heparin (Enoxaparin) or of a phenformin-like substance (Moroxydine Chloride) in primary early recurrent aborters with an impaired fibrinolytic capacity. Thromb Haemost 1995; 73: 362-7.
- 29 Riyazi N, Leeda M, de Vries JI, Huijgens PC, van Geijn HP, Dekker GA. Low-molecular-weight heparin combined with aspirin in pregnant women with thrombophilia and a history of preeclampsia or fetal growth restriction: a preliminary study. Eur J Obstet Reprod Biol 1998; 80: 49-54.
- 30 Eldor A, Kupferminc MJ, Steinman N, Many A, Baram A, Jaffa A, Fait G, Lessing JB. High incidence of thrombophilia in women with obstetric complications and the beneficial effects of LMW heparin and aspirin in subsequent pregnancies. Blood. 1998 92. (suppl 01): 556a (Abstr).
- 31 Hunt BJ, Doughty HA, Majumdar G, Copplestone A, Kerslake S, Buchanan N, Hughes G, khamashta M. Thromboprophylaxis with low molecular weight heparin (Fragmin) in high-risk pregnancies. Thromb Haemost 1997; 77: 39-41.