Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update

Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9 (2-9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand's and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects. All patients with thrombophilia were treated with preconception ASA at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin/LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 24 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U/day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. All patients were carefully monitored with CBC and platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1-4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.