Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke

• Type of Material: Article
• Authors: Hyacinth Hyacinth, Emory University; Robert J. Adams, Medical University of South Carolina; Charles S. Greenberg, Medical University of South Carolina; Jenifer H. Voeks, Medical University of South Carolina; Allyson Hill, College of Charleston; Jacqueline M Hibbert, Morehouse School of Medicine; Beatrice E. Gee, Morehouse School of Medicine
• Language: English
• Date: 2015-08-25
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Hyacinth et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0134193
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 10
• Issue: 8
• Start Page: e0134193
• End Page: e0134193
• Grant/Funding Information: National Institute on Minority Health and Health Disparities (NIMHD) Grant Number 8 U54 MD007588-04 (Formerly Grant Number U54 RR026137) from the National Centre for Research Resources (NCRR); NIMHD Grant Number S21 MD000101-05; MUSC/Department of Defense Cooperative Agreement (SE VIEW) number: W81XWH-10-2-0057; The National Centre for Advancing Translational Sciences (NCATS) of the National Institutes of Health, under Award Number UL1TR000454; Cooperative Agreements with the National Heart, Lung, and Blood Institute (U10 HL 52193 and U10 HL 52016); NIH/NHLBI grant number R21HL092358 and NIH/NCRR grant number 5P20RR0111044, pilot; Children's Healthcare of Atlanta Friends Pilot Project Award, Emory/Pediatrics Pilot project, grant number 00051285
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, General

Abstract

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke.