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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

Plots of coagulation biomarker levels or TCD velocity against total number of PRBC transfusions received over the course of the trial.von Willibrand Factor (vWF) (A), thrombin antithrombin (TAT) complex (B), D-dimer (C) levels and TCD velocity (D) All 3 biomarkers and TCD velocity show significant negative correlation with number of blood PRBC transfusion. Note in the figure the almost clear separation of subjects randomized to no transfusion (open diamond) and transfusion (solid circles) arms based on the number of PRBC transfusions received. Standard care arm = Open diamond. Transfusion arm = Solid circle.
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pone.0134193.g004: Plots of coagulation biomarker levels or TCD velocity against total number of PRBC transfusions received over the course of the trial.von Willibrand Factor (vWF) (A), thrombin antithrombin (TAT) complex (B), D-dimer (C) levels and TCD velocity (D) All 3 biomarkers and TCD velocity show significant negative correlation with number of blood PRBC transfusion. Note in the figure the almost clear separation of subjects randomized to no transfusion (open diamond) and transfusion (solid circles) arms based on the number of PRBC transfusions received. Standard care arm = Open diamond. Transfusion arm = Solid circle.

Mentions: We used partial correlation to test the associations between the number of blood transfusions received, TCD velocity and hematological variables (white cell, red cell and platelet counts, also Hb and HbF level) to levels of biomarkers of coagulation activation and thrombin generation at study exit, adjusted for baseline levels. Figs 3 and 4 shows the result of those tests that were statistically significant. Fig 3A and 3B shows that there was a significant positive correlation between TCD velocity and both serum vWF and TAT levels (r = 0.36, p = 0.0028) and (r = 0.27, p = 0.025), respectively. There was a trend to a positive correlation (r = 0.22, p = 0.079) between serum D-dimer levels and TCD velocity (Fig 3C). These results show a relationship between biomarkers of coagulation activation and TCD velocity.


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)

Plots of coagulation biomarker levels or TCD velocity against total number of PRBC transfusions received over the course of the trial.von Willibrand Factor (vWF) (A), thrombin antithrombin (TAT) complex (B), D-dimer (C) levels and TCD velocity (D) All 3 biomarkers and TCD velocity show significant negative correlation with number of blood PRBC transfusion. Note in the figure the almost clear separation of subjects randomized to no transfusion (open diamond) and transfusion (solid circles) arms based on the number of PRBC transfusions received. Standard care arm = Open diamond. Transfusion arm = Solid circle.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134193.g004: Plots of coagulation biomarker levels or TCD velocity against total number of PRBC transfusions received over the course of the trial.von Willibrand Factor (vWF) (A), thrombin antithrombin (TAT) complex (B), D-dimer (C) levels and TCD velocity (D) All 3 biomarkers and TCD velocity show significant negative correlation with number of blood PRBC transfusion. Note in the figure the almost clear separation of subjects randomized to no transfusion (open diamond) and transfusion (solid circles) arms based on the number of PRBC transfusions received. Standard care arm = Open diamond. Transfusion arm = Solid circle.
Mentions: We used partial correlation to test the associations between the number of blood transfusions received, TCD velocity and hematological variables (white cell, red cell and platelet counts, also Hb and HbF level) to levels of biomarkers of coagulation activation and thrombin generation at study exit, adjusted for baseline levels. Figs 3 and 4 shows the result of those tests that were statistically significant. Fig 3A and 3B shows that there was a significant positive correlation between TCD velocity and both serum vWF and TAT levels (r = 0.36, p = 0.0028) and (r = 0.27, p = 0.025), respectively. There was a trend to a positive correlation (r = 0.22, p = 0.079) between serum D-dimer levels and TCD velocity (Fig 3C). These results show a relationship between biomarkers of coagulation activation and TCD velocity.

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