Original ArticlesThrombogenesis in sickle cell disease☆,★
Section snippets
Subjects
Thirty-three subjects with SCD (hemoglobin SS), 11 during episodes of pain and 22 while pain-free, were studied for in vivo platelet activation and platelet and red blood cell thrombogenic activities by using flow cytometry. Concurrent studies for circulating plasma markers of platelet secretion, thrombin generation, and fibrinolysis were done with enzyme-linked immunosorbant assays.
Pain episodes were defined as acute events characterized by diffuse pain occurring in the extremities, back,
Flow cytometric methods for detecting activated platelets
Three-color flow cytometric analysis of periph-eral blood labeled with lineage-specific probes readily discriminated erythrocytes, leukocytes, and platelets by immunofluorescence and light-scatter properties. The flow cytometric detection of platelets activated in vitro is shown in Fig 1.
DISCUSSION
The present study establishes that patients with SCD demonstrate increased platelet activation, thrombin generation, and fibrinolysis during clinically quiescent periods and that during SCD pain episodes these thrombogenic activities become amplified. Both platelets and erythrocytes contribute procoagulant activities promoting the generation of thrombin, leading to the development of thrombo-occlusive complications of SCD. This interpretation is supported by significant correlations among the
Acknowledgements
We thank Scott Clark, PhD, for assistance with the statistical analysis.
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Supported by grants 5 P60 HL48482 and 1R01 HL61703 from the National Institutes of Health.
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Reprint requests: James Eckman, MD, Emory University School of Medicine, Department of Hematology and Oncology, 69 Butler St, SE, Atlanta, GA 30303.