Diagnosis and Management of Prenatal Hereditary Pyropoikilocytosis.

Abstract

Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia caused by variants in SPTA1, SPTB, and EPB41. These weaken horizontal interactions in the erythrocyte cytoskeleton, causing membrane fragmentation and splenic sequestration. It will readily cause fetal anemia and often hydrops fetalis. Prenatal diagnosis requires first ruling out immune and other non-immune causes of fetal anemia. Diagnosis is made using characteristic blood smear morphology, ideally examined on a native blood sample, paired with exome sequencing. When these are inconclusive, laboratory tests such as ektacytometry and eosin-5-maleimide flow cytometry can help distinguish HPP from other membranopathies. Prenatal disease almost always requires intrauterine transfusion. In the neonatal period, HPP will continue to cause severe anemia, and patients usually remain transfusion dependent until definitive intervention. For some patients, splenectomy relieves or reduces their transfusion requirements while others continue to be transfusion dependent. This response may be related to a patient's genotype. Allogeneic stem cell transplant (SCT) is an emerging therapy that has been performed in a few patients with good outcomes. We report three additional patients with membranopathy who have undergone SCT. All were diagnosed prenatally and required transfusion support pre- and post-natally. Following SCT, all patients became transfusion independent and are doing well.