Enoxaparin for prevention of unexplained recurrent miscarriage: A multicenter randomized double-blind placebo-controlled trial

Blood

Volumn 125, Issue 14, 2015, Pages 2200-2205

  Pasquier, Elisabeth ^a   De Saint Martin, Luc ^a   Bohec, Caroline ^b   Chauleur, Céline ^c   Bretelle, Florence ^d   Marhic, Gisèle ^e   Le Gal, Grégoire ^e   Debarge, Véronique ^f   Lecomte, Frédéric ^g   Denoual Ziad, Christine ^h   Lejeune Saada, Véronique ⁱ   Douvier, Serge ^j   Heisert, Michel ^k   Mottier, Dominique ^e  

^a BREST UNIVERSITY HOSPITAL   (France)

^b Service de Radiologie   (France)

^c UNIVERSITÉ JEAN MONNET   (France)

^d AIX MARSEILLE UNIVERSITY   (France)

^e SERVICE DE RHUMATOLOGIE   (France)

^f LILLE UNIVERSITY HOSPITAL   (France)

^g Quimper ICU   (France)

^h CHU Clemenceau   (France)

ⁱ HÔPITAL NECKER ENFANTS MALADES   (France)

^j DIJON UNIVERSITY HOSPITAL   (France)

^k Groupe Hospitalier Sud Reunion   (France)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ENOXAPARIN; PLACEBO; ANTICOAGULANT AGENT; LOW MOLECULAR WEIGHT HEPARIN;

ADULT; ARTICLE; CONGENITAL DISORDER; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; ECTOPIC PREGNANCY; EPISTAXIS; FEMALE; FETUS DEATH; GESTATIONAL AGE; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; INJECTION SITE REACTION; LIVE BIRTH; MAJOR CLINICAL STUDY; MULTICENTER STUDY; PREECLAMPSIA; PREGNANT WOMAN; PREMATURE LABOR; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SKIN MANIFESTATION; SMALL FOR DATE INFANT; SPONTANEOUS ABORTION; VAGINA BLEEDING; ABORTION, HABITUAL; CLINICAL TRIAL; FOLLOW UP; PREGNANCY; PREGNANCY COMPLICATIONS; PROGNOSIS;

ABORTION, HABITUAL; ADULT; ANTICOAGULANTS; DOUBLE-BLIND METHOD; ENOXAPARIN; FEMALE; FOLLOW-UP STUDIES; GESTATIONAL AGE; HEPARIN, LOW-MOLECULAR-WEIGHT; HUMANS; LIVE BIRTH; PREGNANCY; PREGNANCY COMPLICATIONS; PROGNOSIS;

EID: 84926620874     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-11-610857     Document Type: Article

References (36)

1. Stirrat GM. Recurrent miscarriage. Lancet. 1990;336(8716):673-675.
2. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368(9535):601-611.
3. Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. N Engl J Med. 2010;363(18):1740-1747.
4. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234-1243.
5. Farquharson RG, Jauniaux E, Exalto N; ESHRE Special Interest Group for Early Pregnancy (SIGEP). Updated and revised nomenclature for description of early pregnancy events. Hum Reprod. 2005;20(11):3008-3011.
6. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-908.
7. Robertson L, Wu O, Langhorne P, et al; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132(2):171-196.
8. Kovalevsky G, Gracia CR, Berlin JA, Sammel MD, Barnhart KT. Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med. 2004;164(5):558-563.
9. Gris JC, Mercier E, Quéré I, et al. Low-molecularweight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood. 2004;103(10):3695-3699.
10. Pasquier E, de Saint Martin L, Le Gal G. Antithrombotic medications and recurrent miscarriage. N Engl J Med. 2010;363(9):887, author reply 888.
11. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
12. Brigham SA, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod. 1999;14(11):2868-2871.
13. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326(7382):219.
14. DAMOCLES Study Group, NHS Health Technology Assessment Programme. A proposed charter for clinical trial data monitoring committees: helping them to do their job well. Lancet. 2005;365(9460):711-722.
15. Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H. A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. Fertil Steril. 2006;86(2):362-366.
16. Fawzy M, Shokeir T, El-Tatongy M, Warda O, El-Refaiey AA, Mosbah A. Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebocontrolled study. Arch Gynecol Obstet. 2008;278(1):33-38.
17. Badawy AM, Khiary M, Sherif LS, Hassan M, Ragab A, Abdelall I. Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology. J Obstet Gynaecol. 2008;28(3):280-284.
18. Kaandorp SP, Goddijn M, van der Post JA, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010;362(17):1586-1596.
19. Clark P, Walker ID, Langhorne P, et al; Scottish Pregnancy Intervention Study (SPIN) collaborators. 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):4162-4167.
20. Visser J, Ulander VM, Helmerhorst FM, et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial. Thromb Haemost. 2011;105(2):295-301.
21. Giancotti A, La Torre R, Spagnuolo A, et al. Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss. J Matern Fetal Neonatal Med. 2012;25(7):1191-1194.
22. Martinelli I. Low molecular weight heparin in pregnant women with previous obstetrical complications. A multicenter, randomized trial. Pathophysiol Haemost Thromb. 2010;37(Suppl 1):A3.
23. de Jong PG, Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev. 2014;4:CD004734.
24. Rai R, Tuddenham E, Backos M, et al. Thromboelastography, whole-blood haemostasis and recurrent miscarriage. Hum Reprod. 2003;18(12):2540-2543.
25. Laude I, Rongières-Bertrand C, Boyer-Neumann C, et al. Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight. Thromb Haemost. 2001;85(1):18-21.
26. de Saint Martin L, Duchemin J, Bohec C, et al. Increased thrombin generation measured in the presence of thrombomodulin in women with early pregnancy loss. Fertil Steril. 2011;95(5):1813-1815, e1.
27. Tyrell DJ, Kilfeather S, Page CP. Therapeutic uses of heparin beyond its traditional role as an anticoagulant. Trends Pharmacol Sci. 1995;16(6):198-204.
28. Bose P, Black S, Kadyrov M, et al. Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure. Am J Obstet Gynecol. 2005;192(1):23-30.
29. Johann S, Zoller C, Haas S, Blümel G, Lipp M, Förster R. Sulfated polysaccharide anticoagulants suppress natural killer cell activity in vitro. Thromb Haemost. 1995;74(4):998-1002.
30. Constância M, Hemberger M, Hughes J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002;417(6892):945-948.
31. Isermann B, Sood R, Pawlinski R, et al. The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med. 2003;9(3):331-337.
32. Kashif M, Isermann B. Role of the coagulation system in development. Thromb Res. 2013;131(Suppl 1):S14-S17.
33. An J, Waitara MS, Bordas M, et al. Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model. Blood. 2013;121(11):2127-2134.
34. Oberkersch R, Attorresi AI, Calabrese GC. Lowmolecularweight heparin inhibition in classical complement activation pathway during pregnancy. Thromb Res. 2010;125(5):e240-e245.
35. Di Simone N, Di Nicuolo F, Sanguinetti M, et al. Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors. Placenta. 2007;28(4):298-304.
36. Rodger MA, Hague WM, Kingdom J, et al; TIPPS Investigators. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet. 2014;384(9955):1673-1683.