Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan

Abstract

BackgroundHeritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. Unlike in the Caucasian populations, protein S and protein C deficiencies, instead of Factor V Lieden and Prothrombin mutations, are relatively common in the Han Chinese population. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein S deficiency.MethodsDuring 2011–2016, 68 women with recurrent pregnancy loss (RPL) and protein S deficiency (both the free antigen and function of protein S were reduced) were initially enrolled. All the women must have experienced at least three recurrent miscarriages. After excluding those carrying balanced translocation, medical condition such as diabetes mellitus, chronic hypertension, and autoimmune disorders (including systemic lupus erythematosus and anti-phospholipid syndrome), coexisting thrombophilias other than persistent protein S deficiency (including transient low protein S level, protein C deficiency, and antithrombin III), only 51 women with RPL and sole protein S deficiency were enrolled. Initially they were prescribed low dose Aspirin (ASA: 100 mg/day) and unfortunately there were still 39 women ended up again with early pregnancy loss (12 livebirths were achieved though). Low-molecular-weight-heparin (LMWH) was given for the 39 women in a dose of 1 mg/Kg every 12 h from the day when the next clinical pregnancy was confirmed to the timing at least 24 h before delivery. The perinatal outcomes were assessed.ResultsOf 50 treatment subjects performed for the 39 women (i.e. 11 women enrolled twice for two pregnancies), 46 singletons and one twin achieved livebirths. The successful live-birth rate in the whole series was 94 % (47/50). Nineteen livebirths delivered vaginally whereas 28 delivered by cesarean section. The cesarean delivery rate is thus 59.57 %. Emergent deliveries occurred in 3 but no postpartum hemorrhage had been noted.ConclusionsOur pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency.Trial registration ISRCTN64574169. Retrospectively registered 29 Jun 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s12959-016-0118-9) contains supplementary material, which is available to authorized users.

Reply

“…We therefore remind them with courtesy that our conclusion, as stated in the title of our paper, was based on the fact that a much lower fetal fraction of 1.60% was noted in the first test, which was false‐negative, as compared with 5.76% in the second test, which was true‐positive, and LMWH is the only factor that was changed between the two tests. Nevertheless, we agree that further studies regarding fetal fraction and thrombophilia are important because protein‐S deficiency is a common condition in East Asian populations and cfDNA testing for fetal aneuploidy is popular in this part of the world.…”

Low‐molecular‐weight heparin associated with reduced fetal fraction and subsequent false‐negative cell‐free DNA test result for trisomy 21

“…Here we present a false‐negative case of trisomy 21 resulting from low fetal DNA fraction in maternal plasma associated with the use of low‐molecular‐weight heparin (LMWH) treatment for protein‐S deficiency. The case is that of an individual who had participated in a cohort study at our institution (approved by the institutional review board (IRB) with the number: CCH‐IRB‐151209).…”

“…This 39‐year‐old pregnant woman with protein‐S deficiency (a prevalent form of hereditary thrombophilia among the Taiwanese population) who experienced recurrent pregnancy loss (gravida 4, para 0), underwent regular anticoagulation therapy with the LMWH Enoxaparin (1 mg/kg body weight every 12 h) from 7 + 1 weeks' gestation according to our clinical trial and published protocol. She opted for amniocentesis at 15 + 1 weeks (fetal biparietal diameter, 35 mm), which showed 47,XX + 21.…”

“…The case is that of an individual who had participated in a cohort study at our institution (approved by the institutional review board (IRB) with the number: CCH-IRB-151209) 5 .…”

“…The role of LMWH in the treatment of high-risk pregnancy, for example, those with pre-eclampsia, intrauterine growth restriction, antiphospholipid syndrome or recurrent pregnancy loss, is controversial 5 . Our cohort study demonstrated a benefit of LMWH in women with recurrent pregnancy loss and protein-S deficiency 5 .…”