Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin. The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients.Sickle cell disease is considered nowadays as a hypercoagulable state. However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately.The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators already used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age. This test will be used to characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann Hospital.

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin. This is the most common genetic disease in the world. The majority of patients are in Sub-Saharan Africa; however, the increase in migratory movements of populations helps to move patients out of the initial zones of the disease. According to recent data, about 400 patients would be followed in the Belgian hospitals, and about 1 in 1500 newborns in Belgium would be a major carrier of hemoglobinopathies. The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients. Their contribution to the course of the disease is becoming increasingly stressing. Among them are intravascular hemolysis, hyper-adhesion of blood cells to vascular endothelium, inflammation, oxidative stress, vasculopathy and bleeding disorders. Sickle cell disease is considered nowadays as a hypercoagulable state. Indeed, sickle cell patients have a high risk of non-hemorrhagic stroke, thrombosis in the pulmonary arteries and deep vein thrombosis that are otherwise associated with mortality and high morbidity. Many anomalies at various levels in the hemostatic system demonstrate coagulation activation even in clinically stable condition. However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately. This scale is complex, this approach difficult to give a comprehensive and integrated picture of the various disturbances in the system. The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators have used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age. In this cohort high hemostatic potential was related to the rate of circulating microparticles and intravascular hemolysis rate. Studies are underway to look for correlations between the hemostatic potential and clinical complications in this pediatric cohort. The use of thrombin generation test for the study of hemostasis in adult patients with sickle cell disease, and the contribution of coagulation disorders with the occurrence of complications of the disease remain little known. The investigators will therefore: Characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann Search for links between the hemostatic potential and other biological phenomena observed during the disease (intravascular hemolysis, microparticles, vasculopathy, inflammation) Search for correlations with clinical complications Evaluate the effect of treatment (including exchange transfusions) on the hemostatic potential.

This arm will include an approximate number of 50 sickle cell disease patients, homozygous and heterozygous.

Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once, before and after the exsanguinotransfusion.

The following coagulation markers will be assessed in the blood samples: thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.

sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

The following markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each volunteer.

Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.

sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each volunteer.

Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.

sickle cell patients -if exsanguinotransfusion - immediately prior exsanguinotransfusion, within maximum two years time

Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

Will be measured both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.

sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.

The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.

sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time

The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each volunteer.

The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time

The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time

The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status

sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time

The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each volunteer.

Inclusion Criteria: - Sickle cell disease group: Sickle cell disease patients aged over 18 years - Healthy volunteers group: Healthy volunteers, age matching with the sickle cell disease group Exclusion Criteria: - Sickle cell disease group: Pregnant women, dialysis patients, patients with an hepatic impairment, patients under treatments that can interfere with coagulation - Healthy volunteers group: Pregnant women, known chronical disease, acute inflammatory syndrome, hemostasis disorder, abnormal complete blood count

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