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Quantitative assessment of platelet function and clot structure in patients with severe coronary artery disease
P E Greilich1, M E Carr, S L Zekert
1Coagulation Special Studies Laboratory, Department of Anesthesiology, Walter Reed Army Medical Center, Washington, DC.
Insights
Patients with coronary artery disease (CAD) show persistent platelet activation and rigid clots, even with aspirin. New methods reveal this enhanced platelet force development, offering insights into managing CAD's prothrombotic state.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biophysics
Background:
- Patients with coronary artery disease (CAD) exhibit a prothrombotic state linked to platelet hyperreactivity.
- Current methods for assessing hemostatic function in CAD patients are insufficient.
- Platelet activity significantly contributes to the pathophysiology of CAD.
Purpose of the Study:
- To evaluate a novel technique for measuring platelet force development during clot retraction in CAD patients.
- To compare platelet function and clot structure between CAD patients and healthy volunteers.
- To assess the efficacy of aspirin therapy in modulating platelet activity in CAD.
Main Methods:
- Measurement of platelet force development and clot elastic modulus.
- Assays for fibrinopeptide A, D-Dimer, von Willebrand's factor, and thromboxane B2.
- Platelet aggregation studies and bleeding time measurements.
Main Results:
- CAD patients, even on aspirin, demonstrated significantly elevated platelet force development and clot elastic modulus compared to controls.
- Aspirin therapy suppressed thromboxane B2 and prolonged bleeding times but did not normalize platelet force development.
- Elevated levels of fibrinopeptide A, von Willebrand's factor, D-Dimer, and increased fibrin mass-length ratios were observed in CAD patients.
Conclusions:
- Severe CAD is associated with persistent platelet activation and a rigid clot structure, irrespective of aspirin treatment.
- The novel technique of monitoring platelet force development shows promise for assessing enhanced platelet function in CAD.
- Findings highlight the limitations of aspirin in fully controlling platelet hyperreactivity in CAD patients.
Abstract:
The prothrombotic state of patients with coronary artery disease (CAD) can be attributed partially to platelet activity. Management of such patients is hindered by a lack of techniques to assess hemostatic function. This study used a sensitive technique to monitor platelet function by measuring platelet force development during clot retraction. This technique allowed simultaneous measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio (mu), fibrinopeptide A, D-Dimer, von Willebrand's factor, thromboxane A2, platelet aggregation studies, and bleeding times also were performed. Fourteen patients with CAD were compared with 10 healthy volunteers. Despite more than 95% suppression of thromboxane B2 and prolongation bleeding times in patients taking aspirin, force development remained significantly elevated over healthy control patients (8,279 +/- 476 dynes versus 4,857 +/- 380 dynes, p < 0.0006). Patients not taking aspirin had normal bleeding times and force development of 19,110 +/- 3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced platelet aggregation were insensitive to the effect of aspirin in patients with CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were significantly elevated, and fibrin mass-length ratios were significantly larger in patients with CAD. Therefore, despite aspirin therapy, patients with severe CAD have evidence of persistent platelet activation and rigid clot structure. Monitoring of platelet force development may prove useful in delineating enhanced platelet function.