Recurrent Miscarriage Syndrome due to Blood Coagulation Protein/Platelet Defects: Prevalence, Treatment and Outcome Results

Abstract

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.

Improved Outcomes in ART Pregnancies Complicated by Thrombophilia, Treated with Low Molecular Weight Heparin in Comparison to Spontaneously Conceived Low-Risk, Untreated Pregnancies: A Case Control Study

“…In the present study, the magnitude of reduction of the incidence of prematurity, preeclampsia, fetal demise, and IUGR speaks in support of the concept that the cause of the infertility may potentially be the same as the cause of placental insufficiency with all adverse consequences noted in untreated ART pregnancies [19][20][21]. LMWH improves implantation rates in patients with thrombophilia; furthermore, LMWH improves pregnancy outcomes and reduces recurrent pregnancy loss in patients with thrombophilic disorders [22,23].…”

High factor XI, recurrent pregnancy loss, enoxaparin

“…However, lack of benefit of LMWH also has been reported (52,64,65), most importantly in the LMWH-acetylsalicylic acid versus acetylsalicylic acid randomized controlled trial of Laskin et al (52). Although the non-placebo-controlled trials of LMWH (22,(66)(67)(68) and heparin (23) show improvement over untreated previous pregnancies in the same women, ultimate proof of safety and efficacy of thromboprophylaxis in women with recurrent pregnancy lossspontaneous abortion must be delivered by placebo-controlled clinical trials (52).…”

“…Placental thrombosis may be a major final common pathway in recurrent pregnancy loss (12,22,23), interacting with the physiologic thrombophilic hyperestrogenemia of pregnancy to increase risk for thrombosis of the spiral arteries of the uterus, placental ischemia, and fetal loss (5,7,24,25).…”

Study the Correlation Between Polymorphism of MTHFR Thrombophilic Genes and Pregnancy Loss in Ahvaz City

“…It is usually known as a multi-factoral and complicated disease and various danger factors such as genetics, infections, anatomical, hormonal and immune problems are involved in it 4 . Although the cause of this disease may remain unknown in some cases, about 55% of the patients are report to be afflicted with thrombophilic disorders 5 .…”