The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients

Key Points• Among women with pure obstetric APS, late pregnancy complications are more frequent in cases of prior fetal loss.• Late pregnancy complications are more frequent among women treated for pure obstetric APS than among nontreated controls.The incidence of pregnancy outcomes for women with the purely obstetric form of antiphospholipid syndrome (APS) treated with prophylactic low-molecular-weight heparin (LMWH) plus low-dose aspirin (LDA) has not been documented. We observed women without a history of thrombosis who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal loss at or beyond the 10th week.We compared the frequencies of complications during new pregnancies between treated women with APS (n 5 513; LMWH 1 LDA) and women negative for antiphospholipid antibodies as controls (n 5 791; no treatment). Among APS women, prior fetal loss was a risk factor for fetal loss, preeclampsia (PE), premature birth, and the occurrence of any placenta-mediated complication. Being positive for anticardiolipin immunoglobulin M antibodies was a risk factor for any placenta-mediated complication. Among women with a history of recurrent abortion, APS women were at a higher risk than other women of PE, placenta-mediated complications, and neonatal mortality. Among women with prior fetal loss, LMWH 1 LDA-treated APS women had lower pregnancy loss rates but higher PE rates than other women. Improved therapies, in particular better prophylaxis of late pregnancy complications, are urgently needed for obstetric APS and should be evaluated according to the type of pregnancy loss. (Blood. 2014;123(3):404-413)

The protein Z-protein Z-dependent inhibitor complex is a factor Xa inhibitor. Protein Z deficiencies have recently been described in patients with ischemic stroke. As placenta infarction leads to poor pregnancy outcome, we studied protein Z plasma concentrations in nonthrombotic, nonthrombophilic consecutive patients with unexplained pregnancy wastage. A significant amount of protein Z deficiencies was only found in the early fetal loss group (< 1 mg/L; 44 of 200, P < 10 ؊4 ) and mainly in the case of fetal demise between the beginning of the 10th and the end of the 15th week of gestation (odds ratio, 6.7 [3.1-14.8], P < 10 ؊3 ). These deficiencies were not due to partial vitamin K1 deficiency, and at least some of them were constitutional ones. In women, protein Z deficiency may induce an enhanced risk of severe placental insufficiency soon after the connection of maternal and fetal circulations. IntroductionProtein Z is a vitamin K-dependent plasma protein that serves as a cofactor for the control of the coagulation factor Xa by the protein Z-dependent protease inhibitor. 1,2 Protein Z null mice have an apparently normal phenotype, but protein Z deficiency dramatically increases the thrombotic phenotype in mice carrying the factor V Leiden genotype. 3 Studies to determine the role of protein Z in human thrombosis have, to date, led to the description of an association between prior ischemic stroke and protein Z deficiency. 4 Ultrasonographic data indicate that the placenta replaces the yolk sac as the source of blood supply to the embryo from the beginning of the 8th to the end of the 9th week of gestation. 5 From this crucial step, pregnancy outcome is dependent on sustained placental development; thrombosis in the maternal placenta may lead to fetal demise.Here we describe the incidence of protein Z deficiency in women with unexplained pregnancy loss. Study design PatientsAll the women we studied had given their informed consent for participation to our Abnormal Pregnancy Study Program, based on the recruitment of a vast cohort of patients from the South of France with at least one miscarriage/fetal loss, and of healthy parity-and age-matched control subjects (NOHA studies 6-9 ). In this program, they were all investigated for classical prothrombotic factors as described (essential thrombocythemia; antiphospholipid/anticofactor antibodies; dysfibrinogenemia; deficiency in antithrombin, protein C, or protein S; factor V Leiden mutation; 20210A allele in the prothrombin gene; high plasminogen activator inhibitor 1 plasma levels; or hyperhomocysteinemia).We studied 4 groups of consecutive women with negative thrombotic antecedents and prothrombotic factors: 200 patients with unexplained primary recurrent miscarriages before the 8th week of gestation (3 episodes; median age, 26.2 years), 200 patients with one unexplained primary episode of early fetal death from the 10th to the end of the 19th week (median age, 23.1 years), 50 patients with one unexplained primary episode of late fetal death from the beginning ...