Trial Information

Long Term Effects of Erythrocyte Lysis

1. The study will investigate the relationship between tricuspid regurgitation jet
velocity (TRV) and intravascular hemolysis, as measured by serum lactate dehydrogenase
(LDH), in untreated children with severe sickle cell disease (HbSS or Hb
S/β°-thalassemia)

2. The Study will estimate the prevalence of elevated TRV (≥ 2.5 m/s) in untreated
children with severe sickle cell disease (HbSS or Hb S/β°-thalassemia), as measured by
echocardiography.

Secondary objectives for this study include the following:

1. To estimate the prevalence of elevated TRV in children with severe sickle cell disease
(HbSS or Hb S/β°-thalassemia) receiving hydroxyurea or chronic transfusion therapy.

2. To estimate the prevalence of elevated TRV in children with other forms of hemolytic
anemia, including other sickling disorders (such as HbSC or HbS/β+-thalassemia) and
non-sickling hemolytic anemia (such as hereditary spherocytosis).

3. To estimate the prevalence of elevated TRV in adults with non-sickling hemolytic
anemia, with or without splenic function.

4. To investigate the association between TRV and splenic function

5. To investigate the associations between TRV and laboratory parameters of inflammation
and hypercoagulability, such as white blood cell count, platelet count, serum
N-terminal pro-brain natriuretic peptide (NT-proBNP),endothelial dysfunction, and other
markers of hemolysis (bilirubin, plasma free hemoglobin, haptoglobin, etc.)

6. To evaluate genetic determinants of elevated TRV in children and adults with hemolytic
anemia.

7. To investigate changes in TRV and hemolysis over time using serial measurements 2 ± 0.5
years after initial enrollment testing.