Optimizing chronic transfusion therapy for survivors of hemoglobin Barts hydrops fetalis.

Hemoglobin Barts hydrops fetalis (homozygous a-thalassemia) results from deletion of all 4 a-globin genes. It was previously considered a universally fatal condition; however,with recent advances in prenatal care and the availability of intrauterine blood transfusions, an increasing number of patients are now surviving into adulthood. Similar to patients with transfusion-dependent thalassemia due to b-thalassemia (TDT-b), these patients require lifelong and regular transfusions, as the option of curative stem cell transplant may not be available for the majority of these patients. Although the Thalassemia International Federation guidelines recommend a transfusion strategy similar to TDT-b for these patients, no report exists on the optimal transfusion management of patients with homozygous a-thalassemia, which could be referred to as transfusion-dependent thalassemia due to a-thalassemia (TDT-a). In TDT-b, initiation of transfusions results in improvement of anemia and suppression of ineffective erythropoiesis, the main underlying pathophysiologic processes. In early 2014, we critically reviewed the treatment strategy for four patients with homozygous a-thalassemia at our institution who were previously on regular blood transfusions to keep their hemoglobin levels .100 g/L. Research was approved by the institutional review board, and patients gave consent in accordance with the Declaration of Helsinki. All patients had significant splenomegaly, progressive peripheral blood reticulocytosis, and biochemical markers of hemolysis (high lactate dehydrogenase [LDH], aspartate aminotransferase, indirect bilirubin), erythropoiesis (elevated soluble transferrin receptor [STR]), and tissue hypoxia (high serum erythropoietin). In addition, 3 of the 4 showed brain magnetic resonance imaging changes in keeping with “silent” ischemic infarcts (Table 1; Figure 1). On further investigation, hemoglobin analysis (by high-performance liquid chromatography and capillary zone electrophoresis) showed hemoglobin H (Hb H) percentage ranging from 24% to 64% in our patients, with older patients having higher Hb H. Hb H, a tetramer of 4 b-globin chains, has extremely high oxygen affinity and poor tissue oxygen delivery, making it essentially nonfunctional. With the high Hb H levels observed in our chronically transfused patients with homozygous a-thalassemia, we estimated the patients’ “functional”