Palabras clave
abortos recurrentes, trombofilia, heparina
Cómo citar
Grand, B. (2019). ¿Qué sí y qué no aportaron los estudios de trombofilia y heparina en aborto recurrente al 2017?. Revista Hematología, 22(1), 44–54. Recuperado a partir de https://revistahematologia.com.ar/index.php/Revista/article/view/111
Resumen
El aborto recurrente es un evento frecuente que se presenta en un momento inesperado de la vida, generando en la pareja la necesidad de una explicación sobre las causas que puedan haberlo provocado. Es a partir de aquí donde en los últimos 20 años se ha generado una amplia división entre el mundo de la ciencia y el de la vida cotidiana. La enseñanza aportada por el síndrome antifosfolípido obstétrico sobre una base trombótica y su tratamiento con heparina fue rápidamente trasladada al manejo de la abortadora recurrente con y sin trombofilia hereditaria. Recién a partir del 2010 empiezan a publicarse los resultados de los ensayos clínicos randomizados y registrados sobre el uso de heparina en abortadoras con y sin trombofilia. El objetivo de este trabajo es describir los aportes de todos estos estudios al día de la fecha en abortadoras recurrentes: con diagnóstico de SAF, sin trombofilia hereditaria y/o adquirida, sin antifosfolípidos, y con trombofilia hereditaria, para finalmente debatir sobre aquellos puntos que aún quedan por resolverse.
Citas
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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.
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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