The Influence of micro-and Macro Vascular Dysfunction on Clinical Severity in Adults With Sickle Cell Anemia (SS) and Sickle Cell Hemoglobin C Disease (SC)

TSCD patients are characterized by vascular alterations, with vascular function being severely affected. However, the exact contribution of vascular dysfunction in the clinical severity and the risk for frequent vaso-occlusive crises in SCD is unknown. Furthermore the factors involved in this imbalance remain unclear but it is supposed that cerebral hypoxia, the deficit in nitric oxide, abnormal blood rheology, increased microparticles levels, autonomic nervous system imbalance and a low level of physical activity as well as poor physical fitness might be involved.

• Primary outcome: The primary outcome of the present study is to characterize the level of alteration of micro and macro vascular function in SCD (SS, SC and Sß°) adults measured by heat-mediated vasodilation and peripheral perfusion (Laser Doppler system) and pulse wave velocity and to test relationships between this measured vascular function and clinical severity which is based on the rate of vaso-occlusive crisis (severe if ≥ 3 per year), the rate of acute chest syndrome (severe if > 0 per year) and/or the presence of chronic complications.
• Secondary outcomes: To test the existence of relationships between several factors: biological (hematology, blood rheology, nitric oxide and microparticles), physiological (the autonomic nervous system activity measured by Holter electrocardiogram and tissue oxygenation (muscular and cerebral)) and physical activity level (estimated by questionnaire and accelerometer) and physical fitness (estimated by the six minute walk test with oxygen consumption measurements).
• Study design: This study has been designed as biomedical, monocentric prospective and interventional study

Inclusion criteria

• adults ≥ 18 years old,
• medical diagnosed with SCD (genotype SS, SC or Sß°) by isoelectrofocusing or HPLC at clinical steady state at the time of the study (i.e., no blood transfusion within the last three months,
• absence of acute episodes of infection, vaso-occlusive crisis or acute chest syndrome at least one month before inclusion in the study),
• regularly followed by the Sickle Cell Unit of the Academic Hospital of Pointe-à-Pitre (Guadeloupe) and having signed well informed the letter of agreement.

Exclusion criteria

• not at "steady-state";
• pregnancy or breast feeding;
• non-compliant patients to usual care;
• no signed informed consent