Characterization of Erythropoiesis and Iron Metabolism in Young Patients With Hereditary Pyropoikilocytosis: A Multicenter Study From Thailand

BACKGROUND: Hereditary pyropoikilocytosis (HPP) is the most common among rare forms of severe hemolytic anemia in Thailand. Erythropoiesis and iron metabolism in patients with HPP are understudied, leading to a lack of pathology-guided transfusion and iron chelation management. METHODS: We conducted a multicenter cross-sectional study to quantify biomarkers of erythropoiesis and iron metabolism in 46 young patients with HPP and to compare these findings with those observed in 80 HbE/β-thalassemia. Clinical data were collected to identify factors associated with the severity of abnormal erythropoiesis or iron metabolism in patients with HPP. RESULTS: We identified elevated erythroferrone levels in HPP patients, supporting increased erythropoietic activity and consistent with a contribution from ineffective erythropoiesis. These levels were comparable to those observed in HbE/β-thalassemia. Patients with HPP had earlier iron overload than those with HbE/β-thalassemia (median [IQR] age 2.2 [1.9-2.9] vs. 3.4 [2.4-5.2] years, p < 0.001), and this was associated with a higher transfusion burden and a more pronounced hepcidin suppression. Among HPP patients, more severe hepcidin suppression was significantly associated with younger age at diagnosis and initiation of regular transfusion. Hepcidin suppression persisted in HPP patients with splenectomy (n = 23), and its levels were significantly lower than those of patients with intact spleen (n = 23). Additionally, liver iron concentration was strongly correlated with ferritin levels (R = 0.82) in HPP (n = 15). CONCLUSIONS: This study provides new insights into the pathological characteristics of HPP, specifically, comparable levels of erythroferrone and a greater degree of hepcidin suppression than those observed in HbE/β-thalassemia.