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recurrent miscarriage

References for: Causes, evaluation, and treatment.

Medscape Women’s Health 1998 May;3(3):2 (ISSN: 1521-2076) Bick RL; Madden J; Heller KB; Toofanian A

Thrombosis Clinical Center, Department of Medicine (Hematology & Oncology), Presbyterian Hospital of Dallas, Tex., USA.

Blood Coagulation Protein or Platelet Defects

The coagulation protein and platelet defects associated with fetal wastage include factor XIII[9] and factor XII[10] defects; dysfibrinogenemia[11]; antiphospholipid syndrome,[12] including both anticardiolipin antibodies (ACLA) and lupus anticoagulant (LA); plasminogen defects[13]; other fibrinolytic system defects, such as elevated plasminogen activator inhibitor type 1 (PAI-1) or low-tissue plasminogen activator (t-PA)[14,15]; congenital protein S defects; and sticky platelet syndrome.

Factor XIII defects, as well as most cases of dysfibrinogenemia or other hereditary or acquired hemorrhagic defects, lead to inadequate fibrin-induced implantation of the fertilized ovum into the decidua. However, antiphospholipid syndrome, plasminogen defects, fibrinolytic system defects, some cases of dysfibrinogenemia, and other hypercoagulable blood protein and platelet defects are associated with thrombosis of the early placental vessels, precluding viability of the implanted ovum or fetus. It may be postulated, however, that any blood protein or platelet defect associated with hypercoagulability and thrombosis could be associated with placental vascular thrombosis and recurrent fetal loss.[16]

The differential diagnosis of RFL due to blood coagulation protein or platelet defects includes the occurrence of 2 or more unexplained, spontaneous abortions (usually in the first trimester) and a high index of suspicion based on clinical judgment and awareness of the syndrome, followed by appropriate clinical and laboratory evaluation. We have previously reported our experience, including identification and management of women who have had RFL due to blood protein or platelet defects.[16]


Evaluation of Patients with RFL Suspected to Have Blood Protein or Platelet Defects

Given that about 50% to 60% of patients with recurrent miscarriages harbor a coagulation defect and that identification of the defect, followed by appropriate therapy, will lead to normal-term delivery in 98%, the cost of evaluation (about $1200) can be justified. To contain costs of evaluation, patients who are suspected of having blood protein or platelet defects should be evaluated in 2 stages. Stage I consists of a complete history and physical examination, a routine complete blood count, and a panel of those blood protein and platelet defects commonly associated with RFL. If the first panel of blood protein and platelet defect tests is normal, a second panel (stage II) should be considered, consisting of those blood protein defects thought to be more rarely associated with RFL.[16]

Based on our prevalence studies (Table I),[16] a list of stage I blood-protein and platelet-defect assays was generated. A complete outline of panel I and panel II defect assays may be found in Table II.[17] If all tests in panel I are negative, panel II assays should be considered. All abnormal hemostasis results should be repeated at least once for confirmation. Preferred methodologies for these assays are discussed elsewhere in the literature.[16]


Treatment Considerations

All patients found to have a blood-protein or platelet defect associated with recurrent fetal loss caused by hypercoagulability and thrombosis (thrombosis/vasculitis) of placental vessels are treated preconception with low-dose aspirin at 81mg/day. The aspirin is initiated immediately upon (1) diagnosis of recurrent fetal loss; (2) association with a blood protein/platelet defect related to thrombosis; and (3) desire for subsequent pregnancy. To inhibit coagulation factor Xa, which can lead to placental thrombi during pregnancy, a fixed low dose of subcutaneous porcine heparin at 5000 units every 12 hours until term is added to the daily aspirin regimen immediately postconception.[16]

To make administration more comfortable for the patient, the injection volume of heparin should be small (20,000 units/mL), with a high drug concentration. Patients must be instructed as to the proper methods for self-administration of subcutaneous heparin. Both aspirin and heparin are used to term.

Following delivery, patients harboring a defect associated with hypercoagulability and thrombosis usually require ongoing antithrombotic therapy of some type. Therapeutic options depend on the nature of the thrombotic defect and on the patient’s history, if any, of thrombosis.[16] For patients placed on heparin, the plasma heparin levels are monitored by heparin anti-Xa assay.[16]

Recurrent fetal loss due to blood-protein or platelet defects may come about by 2 mechanisms: disorders associated with either a hemorrhagic tendency or a thrombotic tendency.

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