Long Term Effects of Erythrocyte Lysis

Study Overview
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Brief Summary
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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.

Detailed Description
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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) 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: 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. 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). To estimate the prevalence of elevated TRV in adults with non-sickling hemolytic anemia, with or without splenic function. To investigate the association between TRV and splenic function 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.) To evaluate genetic determinants of elevated TRV in children and adults with hemolytic anemia. To investigate changes in TRV and hemolysis over time using serial measurements 2 ± 0.5 years after initial enrollment testing.

Official Title
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Long Term Effects of Erythrocyte Lysis

Conditions
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Sickle Cell Disease, Hemolytic Anemia

Intervention / Treatment
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* Procedure: Clinical Evaluations
* Other: Laboratory Studies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) 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: Previous cardiac surgery Known left ventricle dysfunction (i.e. shortening fraction < 28%) Known right sided congenital heart defect such as atrial septal defect or pulmonary valve stenosis

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Pediatric participants with severe sickle cell disease (HbSS or Hb S/β°-thalassemia) who are not receiving treatment, e.g., hydroxyurea or chronic transfusions | Procedure: Clinical Evaluations<br>* All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.<br>Other: Laboratory Studies<br>* Blood for: Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array, Serum for: Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha Plasma for: Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1 Urine for: Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin<br>|
| 2<br>Pediatric participants with other forms of SCD or severe sickle cell disease patients (HbSS or Hb S/β°-thalassemia) being treated with hydroxyurea or chronic transfusions | Procedure: Clinical Evaluations<br>* All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.<br>Other: Laboratory Studies<br>* Blood for: Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array, Serum for: Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha Plasma for: Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1 Urine for: Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin<br>|
| 3<br>Pediatric and adult participants with other non-sickling hematological disorders | Procedure: Clinical Evaluations<br>* All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.<br>Other: Laboratory Studies<br>* Blood for: Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array, Serum for: Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha Plasma for: Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1 Urine for: Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1.To 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 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Hemolytic Anemia, Hemolysis