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 de fects, and 10% to 15% to anatomical defects. Recurrent mis carriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, pre- screened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evalu ation. 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 pro coagulant 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 plasmin ogen 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, -ethanol amine, -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 miscar riage 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.