long term effects of erythrocyte lysis

Conditions: Sickle Cell Disease; Hemolytic Anemia

Summary: 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.

Eligibility criteria:
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

Keywords: sickle cell disease, hemolytic anemia hemolysis