Long Term Effects of Erythrocyte Lysis
Long Term Effects of Erythrocyte Lysis
In this prospective observational trial, participants with chronic hemolysis will be assessed
 with echocardiogram for elevated tricuspid jet velocity and other evidence of pulmonary
 hypertension. Participants will have laboratory studies evaluating: severity of hemolysis,
 splenic function, inflammation, endothelial dysfunction, and hypercoagulability. There will
 be 3 main categories of participants enrolled in this study: (1) pediatric participants with
 severe sickle cell disease (SCD) (HbSS, HbS/β° thalassemia ) who are not receiving treatment
 (e.g., hydroxyurea or chronic transfusions); (2) pediatric participants with other forms of
 SCD or severe SCD (HbSS, HbS/β° thalassemia) patients being treated with hydroxyurea or
 chronic transfusions; and (3) pediatric and adult participants with other non-sickling
 hematological disorders.
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.
Inclusion Criteria:

 1. Established Diagnosis of Hemolysis

 -  Sickle Cell Disease (e.g., HbSS, HbS/β-thalassemia, HbSC)

 -  Other conditions with hemolysis (e.g., RBC membranopathies, enzymopathies,
 unstable hemoglobinopathies, PNH)

 2. Age

 -  SCD participants: 5 years of age up to 19th birthday

 -  All other participants: 5 years of age and up (no age limit)

 Exclusion Criteria:

 1. Previous cardiac surgery

 2. Known left ventricle dysfunction (i.e. shortening fraction < 28%)

 3. Known right sided congenital heart defect such as atrial septal defect or pulmonary
 valve stenosis