Association of coagulation activation with clinical complications in sickle cell disease

Kenneth I Ataga, Julia E Brittain, Payal Desai, Ryan May, Susan Jones, John Delaney, Dell Strayhorn, Alan Hinderliter, Nigel S Key, Kenneth I Ataga, Julia E Brittain, Payal Desai, Ryan May, Susan Jones, John Delaney, Dell Strayhorn, Alan Hinderliter, Nigel S Key

Abstract

Background: The contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD.

Design and methods: Plasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records.

Results: No significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sβ⁰ thalassemia and SC/Sβ+ thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sβ⁰ thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactate dehydrogenase, NT-proBNP and history of stroke; soluble CD40 ligand was associated with WBC count and platelet count; and MPTF procoagulant activity was associated with hemoglobin and history of acute chest syndrome.

Conclusions: This study supports the association of coagulation activation with hemolysis in SCD. The association of D-dimer with a history of stroke suggests that coagulation activation may contribute to the pathophysiology of stroke in clinically severe forms of SCD. More research is needed to evaluate the contribution of coagulation and platelet activation to clinical complications in SCD.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. TAT is correlated with D-dimer…
Figure 1. TAT is correlated with D-dimer in sickle cell disease.
Plasma TAT is significantly correlated with plasma D-dimer in our study cohort (r = 0.66; p

Figure 2. TAT is correlated with lactate…

Figure 2. TAT is correlated with lactate dehydrogenase in sickle cell disease.

TAT is correlated…

Figure 2. TAT is correlated with lactate dehydrogenase in sickle cell disease.
TAT is correlated with lactate dehydrogenase in our study cohort (r = 0.57, p

Figure 3. D-dimer is correlated with lactate…

Figure 3. D-dimer is correlated with lactate dehydrogenase in sickle cell disease.

D-dimer is correlated…

Figure 3. D-dimer is correlated with lactate dehydrogenase in sickle cell disease.
D-dimer is correlated with lactate dehydrogenase in our study cohort (r = 0.56; p

Figure 4. D-dimer is correlated with soluble…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.

D-dimer is correlated…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.
D-dimer is correlated with soluble VCAM-1 in our study cohort (r = 0.49; p
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References
    1. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91–96. - PubMed
    1. Stein PD, Beemath A, Meyers FA, Skaf E, Olson RE. Deep venous thrombosis and pulmonary embolism in hospitalized patients with sickle cell disease. Am J Med. 2006;119:897.e7–e11. - PubMed
    1. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors and mortality. Am J Obst Gynecol. 2006;194:1311–1315. - PubMed
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Figure 2. TAT is correlated with lactate…
Figure 2. TAT is correlated with lactate dehydrogenase in sickle cell disease.
TAT is correlated with lactate dehydrogenase in our study cohort (r = 0.57, p

Figure 3. D-dimer is correlated with lactate…

Figure 3. D-dimer is correlated with lactate dehydrogenase in sickle cell disease.

D-dimer is correlated…

Figure 3. D-dimer is correlated with lactate dehydrogenase in sickle cell disease.
D-dimer is correlated with lactate dehydrogenase in our study cohort (r = 0.56; p

Figure 4. D-dimer is correlated with soluble…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.

D-dimer is correlated…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.
D-dimer is correlated with soluble VCAM-1 in our study cohort (r = 0.49; p
Similar articles
Cited by
References
    1. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91–96. - PubMed
    1. Stein PD, Beemath A, Meyers FA, Skaf E, Olson RE. Deep venous thrombosis and pulmonary embolism in hospitalized patients with sickle cell disease. Am J Med. 2006;119:897.e7–e11. - PubMed
    1. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors and mortality. Am J Obst Gynecol. 2006;194:1311–1315. - PubMed
    1. Francis RB. Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. Blood Coagul Fibrinolysis. 1991;2:341–353. - PubMed
    1. Key NS, Slungaard A, Dandelet L, Nelson SC, Moertel C, et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood. 1998;91:4216–4223. - PubMed
Show all 33 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI
Figure 3. D-dimer is correlated with lactate…
Figure 3. D-dimer is correlated with lactate dehydrogenase in sickle cell disease.
D-dimer is correlated with lactate dehydrogenase in our study cohort (r = 0.56; p

Figure 4. D-dimer is correlated with soluble…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.

D-dimer is correlated…

Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.
D-dimer is correlated with soluble VCAM-1 in our study cohort (r = 0.49; p
Similar articles
Cited by
References
    1. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91–96. - PubMed
    1. Stein PD, Beemath A, Meyers FA, Skaf E, Olson RE. Deep venous thrombosis and pulmonary embolism in hospitalized patients with sickle cell disease. Am J Med. 2006;119:897.e7–e11. - PubMed
    1. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors and mortality. Am J Obst Gynecol. 2006;194:1311–1315. - PubMed
    1. Francis RB. Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. Blood Coagul Fibrinolysis. 1991;2:341–353. - PubMed
    1. Key NS, Slungaard A, Dandelet L, Nelson SC, Moertel C, et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood. 1998;91:4216–4223. - PubMed
Show all 33 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 4. D-dimer is correlated with soluble…
Figure 4. D-dimer is correlated with soluble VCAM-1 in sickle cell disease.
D-dimer is correlated with soluble VCAM-1 in our study cohort (r = 0.49; p

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