Among patients with fetal and neonatal alloimmune thrombocytopenia (FNAIT), the presence of anti-GPIbα antibodies is associated with recurrent miscarriages, according to findings from a study presented at the Thrombosis & Hemostasis Summit of North America 2024 (THSNA 2024).
Understanding recurrent miscarriages
A recurrent miscarriage is defined as “the loss of three or more consecutive pregnancies before the 20th week of gestation.” It is recognized that between 1% and 2% of all couples experience recurrent miscarriages.
Recognizing that more than half of all cases of recurrent miscarriages cannot be explained, the researchers sought to describe the cases of three women who experienced repeated miscarriages.
Although FNAIT is known to be a suspected cause of miscarriages among pregnant patients, clinical data on the association remain sparse. In fact, “FNAIT is classically defined by maternal antibody generation against specific human platelet antigens (HPAs) on fetal platelets, leading to thrombocytopenia, severe bleeding diatheses, and other obstetric complications.”
Read more about FNAIT testing and diagnosis
Anti-GPIbα antibodies detected in two out of three patients
Between 70% and 90% of all cases of FNAIT are associated with maternal alloantibodies that target integrin β3 (HPA-1a), whereas those cases linked to GPIbα antibodies (HPA-2b) are extremely rare and reported in fewer than 1% of patients.
In the current study, the investigators aimed to explore whether anti-GPIbα antibodies are related to recurrent miscarriages in humans. They evaluated the sera obtained from women who had experienced “unexplained recurrent miscarriages” for the presence of antiplatelet antibodies and examined the effect on platelet function.
The three women in the study were recruited from the Prenatal Diagnosis and Medical Genetics Program in the Department of Obstetrics and Gynecology at Mount Sinai Hospital, located in Toronto, Ontario, Canada. Although a standard workup was conducted in the three participants, a definitive cause for their repeated miscarriages could not be established.
A monoclonal antibody immobilization of platelet antigen (MAIPA) assay and flow cytometry were used for detection of immunoglobulin G (IgG) against specific antigens in the serum from each of the patients.
Results of the analysis showed that based on MAIPA assays, high levels of antiplatelet antibodies were observed in two of the three patients. Of note, the serum from the first patient contained anti-GPIbα IgG. The serum from the second patient exhibited IgG against both GPIbα and integrin β3. In the third patient, there was no antiplatelet IgG detected.
Donor platelets that were incubated with sera from patient one and patient two, but not from patient three, induced platelet activation and desialylation. Notably, purified IgG from these two patients did the same, thus confirming that the effect on platelets was IgG-specific.
“We detected anti-GPIbα antibodies in [two of three] patients experiencing unexplained recurrent miscarriages, which may explain the paucity of such cases in neonates,” the authors noted. “GPIbα antibodies could cause miscarriage by inducing fetal platelet activation, promoting pathological blood clotting, and impaired blood flow to the placenta,” they explained. “These initial findings provide the first evidence that anti-GPIbα antibodies in FNAIT are associated with recurrent miscarriages in humans,” they concluded.
