Hemostasis in Sickle Cell Disease--Infancy to Adulthood

To assess in older children and adults with sickle cell disease (SCD) whether intrinsic activation (relevant to the origin of pain and acute inflammation) occurs only during vasocclusive crisis (VOC).

Study Overview

• Status: Completed
• Conditions: Anemia, Sickle Cell; Blood Disease

Detailed Description

BACKGROUND:

Investigations into hemostatic abnormalities associated with sickle cell disease have been numerous. The data suggested that thrombin generation and fibrin formation were increased during steady state, with conflicting data whether further activation occurred in vaso-occlusive crisis. Platelet activation during VOC occurred, with variable findings during steady state. A selective, concomitant evaluation of the hemostatic pathways i.e. intrinsic, tissue factor (TF) or extrinsic activation, fibrinolysis, and platelet-endothelial activation had not been reported. Neither had a longitudinal evaluation been performed in infants during the unique transition period when HbF levels fall from 70 to 80 percent to less than 10 percent.

The study was part of an initiative on "Coagulation, Platelets and Thrombosis in Sickle Disease Pathophysiology". The Request for Applications was released in October 1994.

DESIGN NARRATIVE:

The studies used appropriate 'negative' and 'positive' control groups. Studies included intrinsic markers [kininogen profiling, high molecular weight kininogen (HK) and low molecular weight kininogen (LK) cleavages, western blotting of HK and LK, and kallikrein-alpha2 macroglobulin; extrinsic markers [TF and factor V11a]; other activation and fibrinolytic markers [prothrombin F1.2, FPA, TAT, tPA, PAI-I, D-dimer and plasma alpha2 antiplasmin]; platelet- endothelial markers [evaluation of activation dependent epitopes]. Unequivocal demonstration of contact pathway activation during VOC provided a crucial link between VOC and its accompanying phenomenon including pain, and inflammation. Finally, the studies provided a unique perspective on the continuum of hemostatic changes that unfolded during the course of SCD, and those that developed as vascular insufficiencies supervened in the adult.

The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

No eligibility criteria

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Marie Stuart, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: July 1, 1995
• Study Completion (Actual): July 1, 1998

Study Registration Dates

• First Submitted: May 25, 2000
• First Submitted That Met QC Criteria: May 25, 2000
• First Posted (Estimate): May 26, 2000

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: March 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Hematologic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: 4310; R01HL055185 (U.S. NIH Grant/Contract)