New research suggests fetal and neonatal alloimmune thrombocytopenia (FNAIT), a rare but serious bleeding disorder, may be both triggered and potentially prevented through treatment options similar to those in hemolytic disease of the fetus and newborn (HDFN), according to a study published recently in Blood.
Results indicate that fetal-maternal hemorrhage can initiate the immune response that causes FNAIT, and that targeted preventive treatment may stop it before harm occurs.
FNAIT develops when a pregnant person’s immune system produces antibodies against fetal platelet proteins, most commonly HPA-1a. These antibodies can cross the placenta and destroy fetal platelets, leading to dangerously low platelet counts and, in severe cases, life-threatening bleeding such as intracranial hemorrhage. Unlike the related condition HDFN, the triggers of FNAIT have remained unclear, making prevention difficult.
“It has proven difficult to determine the nature, dose and timing of exposure to fetal HPAs that trigger the maternal alloimmune response during pregnancy, which has hampered efforts to develop and approve preventative therapies for FNAIT,” explained the authors of this research.
Read more about the causes and risk factors of FNAIT
In this study, researchers modeled fetal-maternal hemorrhage by transfusing mice with HPA-1a-positive platelets at levels corresponding to mild, moderate and severe fetal blood exposure in humans. They found that moderate and severe exposures, equivalent to about 30 mL and 250 mL of fetal blood, triggered strong immune responses, with production of anti–HPA-1a IgM and IgG antibodies by day 14. Lower exposure levels did not produce the same effect.
Importantly, the immune response that leads to FNAIT was not reduced during pregnancy. Pregnant and nonpregnant mice produced similar levels of antibodies after exposure to HPA-1a-positive platelets. In pregnancies where fetuses carried the HPA-1a antigen, these maternal antibodies caused FNAIT, as shown by significantly lower platelet counts in newborns.
The study also tested a preventive approach using an HPA-1a-specific monoclonal antibody called RLYB212. When given during pregnancy before platelet exposure, this treatment prevented the maternal immune system from becoming sensitized. As a result, newborns were protected from FNAIT and had normal platelet counts. The treatment worked at doses as low as about 1 μg/kg, which is comparable to levels used in related conditions.
Equally important for patients, the preventive antibody did not cause harm when given on its own. In the absence of fetal-maternal hemorrhage exposure, treated pregnancies resulted in normal platelet counts in newborns, suggesting the therapy is safe in this model. For patients and families affected by FNAIT, these findings offer hope that future screening and preventive treatments could reduce the risk of this unpredictable and potentially devastating condition.
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