Are maternal antiplatelet antibodies a prothrombotic condition leading to miscarriage?

Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a condition characterized by thrombocytopenia in the newborn. If severe, the thrombocytopenia can lead to intracranial hemorrhage. FNAIT arises when maternal antibodies specific for platelet antigens, most commonly β3 integrin, cross the placenta and destroy fetal platelets. Surprisingly, few cases of FNAIT are associated with antibodies specific for the platelet antigen GPIbα, which is a common target in patients with immune thrombocytopenia. In this issue of the JCI, Li et al. have identified a potential reason for this - they find that in the majority of pregnant mice, anti-GPIbα antibodies enhance platelet activation and accelerate thrombus formation in the placenta and that this leads to miscarriage.

Figure 1. The effects of maternal alloimmune anti-β3 antibodies and anti-GPIbα antibodies in pregnancy.

Maternal alloimmune antiplatelet antibodies are most commonly directed to the HPA-1a epitope of β3 integrin and can cause FNAIT. This entity is most commonly associated with thrombocytopenia and, in severe cases, neonatal intracerebral hemorrhage. FNAIT associated with anti-GPIbα antibodies has been rarely recognized. In this issue of the JCI, Li et al. report that in mice with anti-GPIbα antibodies, a high percentage of pregnancies results in placental thrombosis due to increased thrombin formation and that this leads to miscarriage (12). In contrast, mouse anti-β3 antibodies were more commonly observed to produce thrombocytopenia and less commonly associated with placental thrombosis and miscarriage. This report suggests that FNAIT may be a cause of thrombosis in addition to hemorrhage and that some antiplatelet antibodies may induce miscarriage.