Modulation of systemic hemostatic parameters by enoxaparin during gestation in women with thrombophilia and pregnancy loss.
Recurrent pregnancy loss (PL) is associated with maternal thrombophilia and prophylaxis with low molecular weight heparin (LMWH) can improve pregnancy outcome in this setting. The aim of this study was to investigate the modulation of systemic hemostatic parameters by enoxaparin in women with recurrent PL and to evaluate plasmatic parameters that would potentially enable monitoring LMWH prophylaxis effect during pregnancy. Study group included 87 women with thrombophilia and PL treated with enoxaparin 40 mg daily vs. 40 mg twice daily. The control group comprised 40 women with normal pregnancies. Blood samples have been collected throughout the period starting at 5-10 weeks of gestation until 6-10 weeks postpartum. The determined plasmatic markers included: anti-Xa activity, total and free tissue factor pathway inhibitor (TFPI), D-dimer, prothrombin fragment 1+2 (PT1+2), activated protein C resistance (APC-SR) and free protein S. Successful pregnancy outcome was recorded in 70 (80.5%) women treated with enoxaparin, without correlation to enoxaparin dosage. Seventeen women (19.5%) had pregnancy loss at 16+/-7 (6-32) weeks of gestation. Anti-Xa levels at 10-15 weeks of gestation were higher (0.39+/-0.38 u/ml) in the successful pregnancy outcome group compared to the abortion group (0.22+/-0.2 u/ml). Prophylactic anti-Xa activity levels (0.28+/-0.13 u/ml) were documented from 15 weeks of gestation until delivery in the successful pregnancy outcome group. Significant increase in anti-Xa, total TFPI and free TFPI levels (P<0.001) was achieved after beginning of LMWH prophylaxis in successful pregnancy outcome group but not in the abortion group. D-dimer and PT1+2 levels appeared to be significantly increased while APC-SR and free protein S levels gradually decreased during pregnancy, with no difference between study groups. These results suggest that LMWH prophylaxis during pregnancy enables modulation of systemic hemostatic parameters via inhibition of factor Xa and increase in plasmatic total and free TFPI levels.
Sarig
Galit
G
Thrombosis and Hemostasis Unit, Rambam Medical Center, Haifa 31096, Israel. g_sarig@rambam.health.gov.il
Blumenfeld
Zeev
Z
Leiba
Ronit
R
Lanir
Naomi
N
Brenner
Benjamin
B
D000026:Abortion, Habitual / Q000517:prevention & control*; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D017984:Enoxaparin / Q000008:administration & dosage*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011486:Protein C / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood; D017293:Protein S / Q000378:metabolism; D011516:Prothrombin; D019851:Thrombophilia / Q000188:drug therapy*
D000925:Anticoagulants; D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; D010446:Peptide Fragments; D011486:Protein C; D011498:Protein Precursors; D017293:Protein S; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin