Current Insights Into K-associated Fetal Anemia and Potential Treatment Strategies for Sensitized Pregnancies

K-associated anemic disease of the fetus and newborn (K-ADFN) is a rare but life-threatening disease in which maternal alloantibodies cross the placenta and can mediate an immune attack on fetal red blood cells expressing the K antigen. A considerably more common disease, D-associated hemolytic disease of the fetus and newborn (D-HDFN), can be prophylactically treated using polyclonal alpha-D antibody preparations. Currently, no such prophylactic treatment exists for K-associated fetal anemia, and disease is usually treated with intrauterine blood transfusions. Here we review current understanding of the biology of K-associated fetal anemia, how the maternal immune system is sensitized to fetal red blood cells, and what is understood about potential mechanisms of prophylactic HDFN interventions. Given the apparent challenges associated with preventing alloimmunization, we highlight novel strategies for treating sensitized mothers to prevent fetal anemia that may hold promise not only for K-mediated disease, but also for other pathogenic alloantibody responses.