Unraveling hereditary hemolytic anemia: Clinical sequelae and pathophysiology

Abstract

This thesis was designed to contribute to unraveling various aspects of hereditary hemolytic anemia (HHA), and to outline the first steps towards creating an evidence based framework for future guidelines regarding diagnosis and treatment of HHA. In the first part of the thesis we focused on the clinical burden of HHA. For this we describe quality of life of patients with HHA, as well as organ involvement. including the rare, but dangerous complication pulmonary hypertension. The second part of the thesis was dedicated to the association between clinical symptoms and pathophysiology. For this we studied the relation between hypercoagulability after splenectomy and cell derived membrane enclosed PS-exposing extracellular vesicles. Second, we studied the role of the currently not fully understood elevated levels of red cell 2,3-diphopshoglycerate (2,3-DPG) in SCD and their relation to oxidative stress. In the last part of this thesis we evaluated current diagnostic and treatment strategies for HHA. For this we studied occurence of iron overload, and evaluated the effectiveness of currently used guidelines to diagnose iron overload. Lastly, we describe an inventory of stem cell transplantation as a treatment for pyruvate kinase deficiency.