Coagulation disorders and immunological causes of recurrent miscarriage

Thrombophilia and recurrent miscarriage

The hemostatic system has an important function in the establishment and preservation of
pregnancy. A thrombophilic defect is an aberration in the coagulation system that
predisposes an individual to thrombosis. During the last few years, the function of anti phospholipid syndrome (APS), an acquired thrombophilic defect, has become an recognized and treatable basis of recurrent miscarriage and the potential role of other thrombophilic defects (acquired or inherited) has been explored. The assumed hypothesis is that some cases of recurrent miscarriage and later pregnancy complications are caused by an exessive hemostatic response during pregnancy, causes thrombosis of the uteroplacental vasculature and subsequent fetal death.


Antiphospholipid Antibodies and recurrent miscarriage

Antiphospholipid antibodies (aPLs) are a family of heterogeneous autoantibodies that react with epitopes on proteins that are complexed with negatively charged phospholipids. In the causes of recurrent pregnancy loss, the two most clinically important aPLs are lupus anticoagulant and anticardiolipin antibodies.

APS is the association between aPLs and pregnancy morbidity or vascular thrombosis.
Pregnancy morbidity includes recurrent first-trimester miscarriage, one or more morphologically normal fetal deaths after the 10th week of gestation, and one or more preterm births before the 34th week of gestation as a result of severe preeclampsia, eclampsia, or placental insufficiency.

APS in patients with chronic inflammatory systemic connective tissue disorders, such as systemic lupus erythematosus (SLE), is referred to as "secondary APS." In contrast, "primary APS" affects patients with no identifiable underlying systemic connective tissue disease.

A major characteristic of APS is recurrent miscarriage. In 15% of women with recurrent miscarriage, aPLs (lupus anticoagulant and anticardiolipin IgG or IgM antibodies) are present. In untreated pregnancies, the chance of successful pregnancy outcome in women with aPLs is very poor and the live birth rate may be as low as 10%.

The mechanisms by which aPLs are responsible for adverse pregnancy outcome are diverse, due to their heterogeneity. The earlier explanations of aPL-related pregnancy loss was placental thrombosis. However, thrombosis is neither specific nor generalized. The recent research explains, defective decidualization of the endometrium and abnormal early trophoblastic function and differentiation may be the primary pathologic mechanisms for fetal loss.

Inherited Thrombophilic Defects and recurrent miscarriage

Inherited thrombophilic defects are recognized causes of systemic thrombosis. These defects include activated protein C resistance ; protein C, protein S, and antithrombin III deficiencies; hyperhomocysteinemia; and prothrombin gene mutation. Recently, these defects were reported to be associated with fetal loss and late pregnancy complications. Evidence of this association is largely retrospective, and prospective data are inadequate to prove a causal relationship

Disorders of Maternofetal Alloimmune Relationships and recurrent miscarriage

The assumption that successful pregnancy depends on maternal immunologic tolerance of the fetus and that some cases of recurrent miscarriage is due to failure of maternal alloimmune recognition of the pregnancy has not been substantially proved. No alloimmune mechanisms have been shown indisputably to cause recurrent miscarriage in humans. No clear substantiation supports the hypothesis that HLA incompatibility between couples, the absence of maternal leukocytotoxic antibodies, or the absence of maternal blocking antibodies as a basis of recurrent miscarriage.