Associations of hemolysis and anemia with cardiopulmonary dysfunction in an adult sickle cell disease cohort.

Background: Hemolysis contributes to the anemia of sickle cell disease (SCD). Hemolysis and anemia are distinct but inter-related pathophysiological processes that underlie end-organ dysfunction in this condition. We hypothesized that real-world medical tests would reveal distinct contributions of hemolysis and anemia to certain cardiopulmonary changes in adults with SCD.

Methods: We assessed laboratory and clinical tests of cardiopulmonary function obtained during routine delivery of care in 442 adult SCD patients. We characterized hemolysis by the first principal component (PC1) of reticulocyte percent, lactate dehydrogenase (LDH), aspartate amino transferase (AST) and total bilirubin- the hemolytic component. The relationships of hemoglobin concentration and hemolysis to organ dysfunction were analyzed by multiple regression and path analysis to identify independent associations.

Results: Degree of hemolysis and degree of anemia both associated independently with elevated values for left atrial diameter (LAD) and left ventricular end-diastolic diameter (LVED), and with lower percent predicted forced expiratory volume in first second (FEV1). Degree of hemolysis, but not anemia, associated independently with low values for oxygen saturation, forced vital capacity (FVC), and total lung capacity (TLC)]. Path analysis reinforced the trend by multiple regression for association of both degree of hemolysis and anemia with elevated TRV but not with lower diastolic blood pressure.

Discussion: Analysis of real-world clinical tests suggest that, although they are inter-related, the degrees of hemolysis and of anemia make independent contributions to cardiopulmonary dysfunction and that treatments that specifically target both aspects of sickle cell disease may be of maximal benefit.