Recurrent miscarriage is not associated with a higher prevalence of inherited and acquired thrombophilia.
Abortion, Habitual
/ blood
Activated Protein C Resistance
Adolescent
Adult
Antibodies, Anticardiolipin
/ blood
Antithrombins
/ blood
Case-Control Studies
Factor V
/ analysis
Factor VIII
/ analysis
Female
Humans
Lupus Coagulation Inhibitor
/ blood
Mutation
Pregnancy
Prevalence
Protein C
/ analysis
Prothrombin
/ genetics
Thrombophilia
/ blood
antiphospholipid syndrome
factor V Leiden
meta-analysis
prothrombin
recurrent miscarriage
thrombophilia
Journal
American journal of reproductive immunology (New York, N.Y. : 1989)
ISSN: 1600-0897
Titre abrégé: Am J Reprod Immunol
Pays: Denmark
ID NLM: 8912860
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
11
05
2020
revised:
07
07
2020
accepted:
17
08
2020
pubmed:
30
8
2020
medline:
6
10
2021
entrez:
30
8
2020
Statut:
ppublish
Résumé
Although not being recommended in guidelines, many physicians perform routine screening for thrombophilia in RM patients suspecting a higher prevalence in these patients. The aim of this study was to analyze the prevalence of inherited and acquired thrombophilia in a large cohort of RM patients. Within a multicenter case-control study, n = 820 RM patients and n = 141 controls were included. The prevalence of inherited and acquired thrombophilia including deficiency of protein C/S and antithrombin, elevation of factor VIII activity, APC resistance including mutation in the factor V Leiden gene, mutation in the prothrombin gene and antiphospholipid antibodies were assessed. Further, we performed a meta-analysis of the prevalence of thrombophilia in RM patients including studies between 01/2000 and 01/2020. An antiphospholipid syndrome (APLS) was only present in RM patients. Increased factor VIII concentration was significantly more prevalent in controls (RM vs controls: 5.8% vs 11.0%). None of the other thrombophilia did differ significantly between RM patients and controls. The meta-analysis revealed no significant difference in the occurrence of these thrombophilia between RM patients and controls. The prevalence of inherited thrombophilia does not differ between RM patients and controls. When analyzing rare events like thrombophilia, a high number of patients are needed to obtain reliable results, which might explain contradictory findings in previous studies analyzing small cohorts of RM patients. Despite being less prevalent than previously described, we still recommend screening for APLS as it is associated with severe pregnancy complications.
Substances chimiques
Antibodies, Anticardiolipin
0
Antithrombins
0
Lupus Coagulation Inhibitor
0
Protein C
0
anti-beta 2 glycoprotein I autoantibody
0
factor V Leiden
0
F8 protein, human
839MOZ74GK
Factor V
9001-24-5
Prothrombin
9001-26-7
Factor VIII
9001-27-8
Types de publication
Journal Article
Meta-Analysis
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13327Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Carrington B, Sacks G, Regan L. Recurrent miscarriage: pathophysiology and outcome. Curr Opin Obstet Gynecol. 2005;17:591-597.
Bender Atik R, Christiansen OB, Elson J, et al. ESHRE guideline: recurrent pregnancy loss. Human Reproduction Open. 2018;2018(2). https://doi.org/10.1093/hropen/hoy004
Toth B, Wurfel W, Bohlmann M, et al. Recurrent miscarriage: diagnostic and therapeutic procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050). Geburtshilfe Frauenheilkd. 2018;78:364-381.
Bogdanova N, Markoff A. Hereditary thrombophilic risk factors for recurrent pregnancy loss. J Community Genet. 2010;1:47-53.
Stevens SM, Woller SC, Bauer KA, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016;41:154-164.
Coppola A, Tufano A, Cerbone AM, Di Minno G. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism. Semin Thromb Hemost. 2009;35:683-694.
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;164:558-563.
Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361:901-908.
Baumann K, Beuter-Winkler P, Hackethal A, Strowitzki T, Toth B, Bohlmann MK. Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients. Am J Reprod Immunol. 2013;70:518-521.
Rodger MA, Betancourt MT, Clark P, et al. The association of factor V Leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Medicine. 2010;7:e1000292.
Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med. 2000;342:374-380.
Raziel A, Kornberg Y, Friedler S, Schachter M, Sela BA, Ron-El R. Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss. Am J Reprod Immunol. 2001;45:65-71.
Krabbendam I, Franx A, Bots ML, Fijnheer R, Bruinse HW. Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature. Eur J Obstet Gynecol Reprod Biol. 2005;118:143-153.
Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98:1103-1111.
RCOG. Green-top Guideline No. 17 The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. April 2011, 2011.
Dossenbach-Glaninger A, van Trotsenburg M, Krugluger W, et al. Elevated coagulation factor VIII and the risk for recurrent early pregnancy loss. Thromb Haemost. 2004;91:694-699.
Kutteh WH, Triplett DA. Thrombophilias and recurrent pregnancy loss. Semin Reprod Med. 2006;24:54-66.
Mekinian A, Alijotas-Reig J, Carrat F, et al. Refractory obstetrical antiphospholipid syndrome: features, treatment and outcome in a European multicenter retrospective study. Autoimmun Rev. 2017;16:730-734.
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;4:295-306.
Schreiber K, Radin M, Sciascia S. Current insights in obstetric antiphospholipid syndrome. Curr Opin Obstet Gynecol. 2017;29:397-403.
Kamphuisen PW, Eikenboom JC, Bertina RM. Elevated factor VIII levels and the risk of thrombosis. Arterioscler Thromb Vasc Biol. 2001;21:731-738.
Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114:409-414.
Rai R, Shlebak A, Cohen H, et al. Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage. Human Reproduction (Oxford, England). 2001;16:961-965.
Mtiraoui N, Borgi L, Gris JC, Almawi WY, Mahjoub T. Factor V Leiden, prothrombin G20210A and antibodies against phospholipids in recurrent spontaneous abortion. J Thromb Haemost. 2004;2:1482-1484.
Reznikoff-Etievan MF, Cayol V, Carbonne B, Robert A, Coulet F, Milliez J. Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage. BJOG. 2001;108:1251-1254.
WHO. Recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths. Modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 1977;56:247-253.
Pihusch R, Buchholz T, Lohse P, et al. Thrombophilic gene mutations and recurrent spontaneous abortion: prothrombin mutation increases the risk in the first trimester. Am J Reprod Immunol. 2001;46:124-131.
Marietta M, Facchinetti F, Sgarbi L, et al. Elevated plasma levels of factor VIII in women with early recurrent miscarriage. J Thromb Haemost. 2003;1:2536-2539.
Koster T, Vandenbroucke JP, Rosendaal FR, Briët E, Rosendaal FR, Blann AD. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995;345:152-155.
O'Donnell J, Tuddenham EGD, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost. 1997;77:825-828.
in 't Anker P, Koopman M, Reitsma P, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost. 2000;83:5-9.
Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med. 2000;343:457-462.
Mumford A, Manning R, Laffan M, O'Donnell J. Elevation of FVIII: C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost. 2000;83:10-13.
Ali A, Mohan P, Kareem H, Muhammed MK. Elevated factor VIII levels and shortened APTT in recurrent abortions. J Clin Diagn Res. 2016;10:EC04-06.
Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. N Engl J Med. 2010;363:1740-1747.
Santos TDS, Ieque AL, de Carvalho HC, et al. Antiphospholipid syndrome and recurrent miscarriage: a systematic review and meta-analysis. J Reprod Immunol. 2017;123:78-87.
Cervera R. Antiphospholipid syndrome. Thromb Res. 2017;151(Suppl 1):S43-S47.
Bowman ZS, Wunsche V, Porter TF, Silver RM, Branch DW. Prevalence of antiphospholipid antibodies and risk of subsequent adverse obstetric outcomes in women with prior pregnancy loss. J Reprod Immunol. 2015;107:59-63.
Clark CA, Davidovits J, Spitzer KA, Laskin CA. The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic. Blood. 2013;122(3):341-347; quiz 466.
Mousa HA, Alfirevic Z. Thrombophilia and adverse pregnancy outcome. Croat Med J. 2001;42:135-145.
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;362:1586-1596.
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;2014:CD004734.