Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients

NCT02565082 | Completed

• 1 other identifier: CHUB-Drepanocytose-Hemostatic
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Hemostatic potential; Sickle cell disease; Thrombin generation test

Outcome Measures

Primary Outcomes (24)

• Coagulation markers

  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

• Coagulation markers

  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

• Coagulation markers

  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

• Coagulation markers

  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

• Coagulation markers

  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.

  healthy volunteers: after informed consent signature, within maximum two years time

• Hemolysis markers

  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

• Hemolysis markers

  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

• Hemolysis markers

  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

• Hemolysis markers

  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

• Hemolysis markers

  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.

  healthy volunteers: after informed consent signature, within maximum two years time

• Microparticles level

  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

• Microparticles level

  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

• Microparticles level

  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

• Microparticles level

  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

• Microparticles level

  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.

  healthy volunteers: after informed consent signature, within maximum two years time

• Inflammatory markers

  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

• Inflammatory markers

  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

• Inflammatory markers

  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

• Inflammatory markers

  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

• Inflammatory markers

  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.

  healthy volunteers - after informed consent signature, within maximum two years time

• Vascular markers

  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

• Vascular markers

  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

• Vascular markers

  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

• Vascular markers

  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.

  healthy volunteers - after informed consent signature, within maximum two years time

Study Arms (2)

Sickle cell disease

EXPERIMENTAL

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

Other: Blood sampling - sickle cell patients arm - stable condition; Other: Blood sampling - sickle cell patients arm- exsanguinotransfusion needed; Other: Blood sampling - sickle cell patients arm - vaso-occlusive crisis.

Control

OTHER

This arm will include an approximate number of 30 healthy volunteers.

Other: Blood sampling - healthy volunteers

Interventions

Blood sampling - healthy volunteers OTHER

Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

Control

Blood sampling - sickle cell patients arm - stable condition OTHER

Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

Sickle cell disease

Blood sampling - sickle cell patients arm- exsanguinotransfusion needed OTHER

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

Sickle cell disease

Blood sampling - sickle cell patients arm - vaso-occlusive crisis. OTHER

Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.

Sickle cell disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Brugmann University Hospital: lead

Study Sites (1)

CHU Brugmann Hospital

Brussels, 1020, Belgium

Location

Related Publications (8)

• Le PQ, Ferster A, Cotton F, Vertongen F, Vermylen C, Vanderfaeillie A, Dedeken L, Heijmans C, Ketelslegers O, Dresse MF, Gulbis B. Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management. Med Trop (Mars). 2010 Dec;70(5-6):467-70.

  PMID: 21516988 BACKGROUND

• Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010 Dec 11;376(9757):2018-31. doi: 10.1016/S0140-6736(10)61029-X. Epub 2010 Dec 3.

  PMID: 21131035 BACKGROUND

• Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91-6. doi: 10.1182/asheducation-2007.1.91.

  PMID: 18024615 BACKGROUND

• De Franceschi L, Cappellini MD, Olivieri O. Thrombosis and sickle cell disease. Semin Thromb Hemost. 2011 Apr;37(3):226-36. doi: 10.1055/s-0031-1273087. Epub 2011 Mar 31.

  PMID: 21455857 BACKGROUND

• Manci EA, Culberson DE, Yang YM, Gardner TM, Powell R, Haynes J Jr, Shah AK, Mankad VN; Investigators of the Cooperative Study of Sickle Cell Disease. Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003 Oct;123(2):359-65. doi: 10.1046/j.1365-2141.2003.04594.x.

  PMID: 14531921 BACKGROUND

• Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Beguin S. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003;33(1):4-15. doi: 10.1159/000071636.

  PMID: 12853707 BACKGROUND

• Noubouossie DF, Le PQ, Corazza F, Debaugnies F, Rozen L, Ferster A, Demulder A. Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children. Am J Hematol. 2012 Feb;87(2):145-9. doi: 10.1002/ajh.22206. Epub 2011 Nov 4.

  PMID: 22052675 BACKGROUND

• Noubouossie DC, Le PQ, Rozen L, Debaugnies F, Ferster A, Demulder A. Evaluation of the procoagulant activity of endogenous phospholipids in the platelet-free plasma of children with sickle cell disease using functional assays. Thromb Res. 2012 Aug;130(2):259-64. doi: 10.1016/j.thromres.2011.10.016. Epub 2011 Nov 12.

  PMID: 22079446 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Anne Demulder, MD

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

• Bhavna Mahadeb

  St Pierre Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Responsible of the Hematology laboratory

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: October 1, 2015
• Study Start: September 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 26, 2016

Record last verified: 2016-07

Locations

BE (1)