title: Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke.
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.
authors: Department of Pediatrics Hematology/Oncology, Emory University School of Medicine, Atlanta, GA, United States of America; Stroke Centre, Department of Neurology, Medical University of South Carolina, Charleston, SC, United States of America.
authors: Hyacinth I
authors: HI
authors: Hyacinth
authors: Stroke Centre, Department of Neurology, Medical University of South Carolina, Charleston, SC, United States of America.
authors: Robert J
authors: RJ
authors: Adams
authors: Department of Hematology, Medical University of South Carolina, Charleston, SC, United States of America.
authors: Charles S
authors: CS
authors: Greenberg
authors: Stroke Centre, Department of Neurology, Medical University of South Carolina, Charleston, SC, United States of America.
authors: Jenifer H
authors: JH
authors: Voeks
authors: Department of Biology, College of Charleston, Charleston, SC, United States of America.
authors: Allyson
authors: A
authors: Hill
authors: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States of America.
authors: Jacqueline M
authors: JM
authors: Hibbert
authors: Department of Pediatrics and Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, United States of America; Children's Healthcare of Atlanta, Atlanta, GA, United States of America.
authors: Beatrice E
authors: BE
authors: Gee
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications* / Q000000981:diagnostic imaging; D000990:Antithrombin III / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D001803:Blood Transfusion; D002648:Child; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology*; D013917:Thrombin / Q000378:metabolism*; D017585:Ultrasonography, Doppler, Transcranial; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D014841:von Willebrand Factor; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin