Keywords
recurrent abortions, thrombophilia, heparin
How to Cite
Grand, B. (2019). What yes or not do have thrombophilia and heparin studies added to recurrent abortions up to year 2017?. Journal of Hematology, 22(1), 44–54. Retrieved from https://revistahematologia.com.ar/index.php/Revista/article/view/111
Abstract
Recurrent miscarriage is a sad event for the couple and their family. Since the last 20 years there has been established an important division between science and daily life; women search for a causal etiology and thrombophilia is usually the first answer she receives. What the antiphospholipid syndrome taught us about the thrombotic mechanism of recurrent abortion was generalized and considering the presumed thrombotic pathophysiologic mechanism, the hypothesis of a beneficial effect of antithrombotic agents has arisen and women with either hereditary thrombophilia and/or no thrombophilia but with recurrent abortions are offered heparin therapy despite a low level of evidence. Since 2010 we are receiving information from registered and randomized trials, about the benefit of either studying or not hereditary thrombophilia and the role of heparin in these patients. The objectives of this paper are to make a comprehensive evaluation of the information up to date and to debate the unresolved issues.
References
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2011;105(2):3095-3699.
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11. Pasquier E, de Saint Martin L, Bohec C et al.
Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial. Blood. 2015; 125(14):2200.
12. Schleussner E, Kamin G, Seliger G et al. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.
ETHIG II. Ann Intern Med. 2015; 162:601.
13. Lissalde-Lavigne G, Fabbro-Peray P, Cochery-Nouvellon E et al. Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy:
the matched case-control ‘NOHA first’ study. J Thromb Haemost. 2005; 3: 2178-2184.
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16. Guías SAMeR 2017 - Hacia una Medicina basada en la evidencia científica - Editorial Ascune. 2017.
17. www.thinking wisely.com. Society of Maternal and Fetal Medicine. February 2016.
18. Ormesher L, Simcox LE, Tower C, Greer IA. ‘To test or not to test’, the arguments for and against thrombophilia testing in obstetrics. Obstet Med. 2017 Jun;10(2):61-66.
19. De Jesus G, Agmon-Levin N, Andrade C et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome. Autoimmunity Reviews. 2014, 13:795-813.
20. Marijnen MC, Scheres LJ, Middeldorp S. Aspirin, heparin or both to improve live birth in women with antiphospholipid syndrome and recurrent pregnancy loss. Res Pract Throm Haemost. 2017; 1S1:40 ASY22.3.
21. Bates S. Controversies in thromboprophylaxis for the prevention of recurrent pregnancy complications. Hematología, 2016;20:189-202.
22. Empson M, Lassere M, Craig JC. Prevention of recurrent miscarriages for women with antiphospholipid antibody or lupus anticoagulant. Cochrane database Sys Rev. 2005; 2 CD002859.
23. Middeldorp S. Anticoagulation in pregnancy complications. Hematology. 2014:393-399.
24. de JongP, Quenby S, Bloemenkamp K et al. ALIFE2 study: Low molecular weight heparin for women with recurrent miscarriage and inherited thrombophilia- study protocol for a randomized controlled trial. Trials. 2015; 16:208.
25. Kolte AM, van Oppenraaij RH, Quenby S y col. ESHRE Special Interest Group Early Pregnancy Non-visualized pregnancy losses are prognostically important for unexplained recurrent miscarriage. Hum Reprod. 2014; 29 (5):931-7.
26. Bertolaccini ML, Amengual O, Andreoli L y col. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and
trend. Autoimmun Rev. 2014; 13:917-930.
27. Mastrolia SA, Mazor M, Holcberg G et al. The physiologic anticoagulant and anti-inflamatory role of heparins and their utility in the prevention of pregnancy complications. Thromb Haemost 2015; 113:1236-1246.
28. Pasquier E, de Saint Martin L. Low-Molecular-Weight Heparin for Women with Unexplained Recurrent Pregnancy Loss. Ann Intern Med. 2015;163(6):484-485.
29. Patil R, Gosch K, Shetty S et al. Low-Molecular-Weight Heparin for Women with Unexplained Recurrent Pregnancy Loss. Ann Intern Med. 2015;163(6):483-484.
30. www.grupocaht.com Elegir con Prudencia y Evidencia Nota 3: Aspectos hematológicos del aborto recurrente, enero 2018.
31. Mekinian A, Cohen J, Alijotas-Reig J et al. Unexplained recurrent miscarriages and recurrent implantation failure: is there a place for immunomodulation? Am J Reprod Immunol. 2016; 76:8.
32. Fishel S, Baker D, Elson J et al. Precision Medicine in Assisted Conception: A multicenter observational treatment cohort study of the Annexin A5 Haplotype as a Biomarker for antithrombotic treatment to improve pregnancy outcome. EBio Medicine. 2016; 10:298-304.
33. Fishel S, Baker D, Greer I. LMWH in IVF-Biomarkers and benefits, Thromb Res. 2017; 151 Suppl 1 S65-69.
34. Kutteh W. Novel strategies for the management of recurrent pregnancy loss. Semin Reprod Med. 2015; 33:161-168.
35. Early pregnancy loss. Edited by Roy Farquarson and Mary Stephenson. Cambridge Medicine. Second Edition, 2017.
36. Sugiura-Ogasawara M, Ozaki Y, Katano K y col. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod. 2012; 27(8):2297-303.
3. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen, RHWM, de Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4:295-306.
4. Mak A, Cheung MW, Cheak AA et al. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010; 49:281-288.
5. De Jong P, Goddijn M, Middeldorp S. Antithrombotic therapy for pregnancy loss. Hum Reprod. 2013; 1-18.
6. Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2012; 126(3
Suppl):627S-644S.
7. Kaandorp SP, Goddijn M, van der Post JAM et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010; 362:1586-1596.
8. Clark P, Walker ID, Langhorne P et al. The Scottish Pregnancy Intervention Study: a multicentre randomised controlled trial of low molecular heparin and low dose aspirin in women with recurrent miscarriage. Blood. 2010;115(21):4162-4167.
9. Visser J, Ulander VM, Helmerhost FM et al. Thromboprophilaxis for recurrent miscarriages with or without thrombophilia. HABENOX: a randomised multicentre trial. Thromb Haemost.
2011;105(2):3095-3699.
10. Skeith L, Carrier M, Kaaja R et al. A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia. Blood. 2016; 127(13):1650-1655.
11. Pasquier E, de Saint Martin L, Bohec C et al.
Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial. Blood. 2015; 125(14):2200.
12. Schleussner E, Kamin G, Seliger G et al. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.
ETHIG II. Ann Intern Med. 2015; 162:601.
13. Lissalde-Lavigne G, Fabbro-Peray P, Cochery-Nouvellon E et al. Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy:
the matched case-control ‘NOHA first’ study. J Thromb Haemost. 2005; 3: 2178-2184.
14. Middeldorp S. Inherited thrombophilia: a double-edged sword. Hematology- 2016:1-9.
15. RCOG RCoOaG. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. London: Royal College of Obstetricians and Gynaecologists (RCOG), 2011, 18 p. (Green-top guideline; no. 17).
16. Guías SAMeR 2017 - Hacia una Medicina basada en la evidencia científica - Editorial Ascune. 2017.
17. www.thinking wisely.com. Society of Maternal and Fetal Medicine. February 2016.
18. Ormesher L, Simcox LE, Tower C, Greer IA. ‘To test or not to test’, the arguments for and against thrombophilia testing in obstetrics. Obstet Med. 2017 Jun;10(2):61-66.
19. De Jesus G, Agmon-Levin N, Andrade C et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome. Autoimmunity Reviews. 2014, 13:795-813.
20. Marijnen MC, Scheres LJ, Middeldorp S. Aspirin, heparin or both to improve live birth in women with antiphospholipid syndrome and recurrent pregnancy loss. Res Pract Throm Haemost. 2017; 1S1:40 ASY22.3.
21. Bates S. Controversies in thromboprophylaxis for the prevention of recurrent pregnancy complications. Hematología, 2016;20:189-202.
22. Empson M, Lassere M, Craig JC. Prevention of recurrent miscarriages for women with antiphospholipid antibody or lupus anticoagulant. Cochrane database Sys Rev. 2005; 2 CD002859.
23. Middeldorp S. Anticoagulation in pregnancy complications. Hematology. 2014:393-399.
24. de JongP, Quenby S, Bloemenkamp K et al. ALIFE2 study: Low molecular weight heparin for women with recurrent miscarriage and inherited thrombophilia- study protocol for a randomized controlled trial. Trials. 2015; 16:208.
25. Kolte AM, van Oppenraaij RH, Quenby S y col. ESHRE Special Interest Group Early Pregnancy Non-visualized pregnancy losses are prognostically important for unexplained recurrent miscarriage. Hum Reprod. 2014; 29 (5):931-7.
26. Bertolaccini ML, Amengual O, Andreoli L y col. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and
trend. Autoimmun Rev. 2014; 13:917-930.
27. Mastrolia SA, Mazor M, Holcberg G et al. The physiologic anticoagulant and anti-inflamatory role of heparins and their utility in the prevention of pregnancy complications. Thromb Haemost 2015; 113:1236-1246.
28. Pasquier E, de Saint Martin L. Low-Molecular-Weight Heparin for Women with Unexplained Recurrent Pregnancy Loss. Ann Intern Med. 2015;163(6):484-485.
29. Patil R, Gosch K, Shetty S et al. Low-Molecular-Weight Heparin for Women with Unexplained Recurrent Pregnancy Loss. Ann Intern Med. 2015;163(6):483-484.
30. www.grupocaht.com Elegir con Prudencia y Evidencia Nota 3: Aspectos hematológicos del aborto recurrente, enero 2018.
31. Mekinian A, Cohen J, Alijotas-Reig J et al. Unexplained recurrent miscarriages and recurrent implantation failure: is there a place for immunomodulation? Am J Reprod Immunol. 2016; 76:8.
32. Fishel S, Baker D, Elson J et al. Precision Medicine in Assisted Conception: A multicenter observational treatment cohort study of the Annexin A5 Haplotype as a Biomarker for antithrombotic treatment to improve pregnancy outcome. EBio Medicine. 2016; 10:298-304.
33. Fishel S, Baker D, Greer I. LMWH in IVF-Biomarkers and benefits, Thromb Res. 2017; 151 Suppl 1 S65-69.
34. Kutteh W. Novel strategies for the management of recurrent pregnancy loss. Semin Reprod Med. 2015; 33:161-168.
35. Early pregnancy loss. Edited by Roy Farquarson and Mary Stephenson. Cambridge Medicine. Second Edition, 2017.
36. Sugiura-Ogasawara M, Ozaki Y, Katano K y col. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod. 2012; 27(8):2297-303.
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