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

Hyacinth HI, Adams RJ, Greenberg CS, Voeks JH, Hill A, Hibbert JM, Gee BE - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Baseline and study exit values of von Willibrand Factor (vWF), thrombin antithrombin (TAT) complex, D-dimer and transcranial Doppler (TCD) velocity.HbAA, SNTCD, SC and Tx refers to healthy African American children with normal hemoglobin, sickle cell subjects with normal TCD velocity, STOP subjects randomized to the Standard Care arm and sickle cell subjects randomized to the Transfusion arm respectively. * = p <0.05, ** = p <0.01, *** = p <0.001 and **** = p <0.0001.
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pone.0134193.g001: Baseline and study exit values of von Willibrand Factor (vWF), thrombin antithrombin (TAT) complex, D-dimer and transcranial Doppler (TCD) velocity.HbAA, SNTCD, SC and Tx refers to healthy African American children with normal hemoglobin, sickle cell subjects with normal TCD velocity, STOP subjects randomized to the Standard Care arm and sickle cell subjects randomized to the Transfusion arm respectively. * = p <0.05, ** = p <0.01, *** = p <0.001 and **** = p <0.0001.

Mentions: The clinical characteristics of STOP study subjects whose samples were analyzed are shown in Table 1. Except for median hemoglobin level (7.6 [6.7, 8.9] vs. 7.2 [6.1, 8.5]) mg/dL, which was significantly higher among the Standard Care (SC) (p = 0.021) compared to the Transfusion (Tx) arm, there were no significant differences in baseline characteristics and TCD velocity between study arms. At study exit, median hemoglobin level was significantly higher (8.8 [7.2, 10.4] vs. 8.0 [6.9, 9.3]) mg/dL and median TCD velocity significantly lower (157 [133, 236] vs. 203 [144, 244]) cm/sec among the Tx arm compared to the SC arm, p = 0.006 and 0.002 respectively (Table 1 and Fig 1H). At the one year post-trial time point, those randomized to the Tx arm had significantly lower median TCD velocity (166 [121, 220] vs. 189 [120, 266]) cm/s and body mass index (16.1 [14.2, 21.2] vs. 18.4 [14.0, 26.1]) kg/m2 compared to those randomized to the SC arm, p = 0.034 and 0.031 respectively (Table 1).


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

Hyacinth HI, Adams RJ, Greenberg CS, Voeks JH, Hill A, Hibbert JM, Gee BE - PLoS ONE (2015)

Baseline and study exit values of von Willibrand Factor (vWF), thrombin antithrombin (TAT) complex, D-dimer and transcranial Doppler (TCD) velocity.HbAA, SNTCD, SC and Tx refers to healthy African American children with normal hemoglobin, sickle cell subjects with normal TCD velocity, STOP subjects randomized to the Standard Care arm and sickle cell subjects randomized to the Transfusion arm respectively. * = p <0.05, ** = p <0.01, *** = p <0.001 and **** = p <0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549306&req=5

pone.0134193.g001: Baseline and study exit values of von Willibrand Factor (vWF), thrombin antithrombin (TAT) complex, D-dimer and transcranial Doppler (TCD) velocity.HbAA, SNTCD, SC and Tx refers to healthy African American children with normal hemoglobin, sickle cell subjects with normal TCD velocity, STOP subjects randomized to the Standard Care arm and sickle cell subjects randomized to the Transfusion arm respectively. * = p <0.05, ** = p <0.01, *** = p <0.001 and **** = p <0.0001.
Mentions: The clinical characteristics of STOP study subjects whose samples were analyzed are shown in Table 1. Except for median hemoglobin level (7.6 [6.7, 8.9] vs. 7.2 [6.1, 8.5]) mg/dL, which was significantly higher among the Standard Care (SC) (p = 0.021) compared to the Transfusion (Tx) arm, there were no significant differences in baseline characteristics and TCD velocity between study arms. At study exit, median hemoglobin level was significantly higher (8.8 [7.2, 10.4] vs. 8.0 [6.9, 9.3]) mg/dL and median TCD velocity significantly lower (157 [133, 236] vs. 203 [144, 244]) cm/sec among the Tx arm compared to the SC arm, p = 0.006 and 0.002 respectively (Table 1 and Fig 1H). At the one year post-trial time point, those randomized to the Tx arm had significantly lower median TCD velocity (166 [121, 220] vs. 189 [120, 266]) cm/s and body mass index (16.1 [14.2, 21.2] vs. 18.4 [14.0, 26.1]) kg/m2 compared to those randomized to the SC arm, p = 0.034 and 0.031 respectively (Table 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus