Full Length ArticlePlatelet function as a risk factor for venous thromboembolism in the Framingham Heart Study

- A large study of platelet reactivity with long surveillance for VTE incidence
- Paradoxical association of lower collagen reactivity with higher VTE risk
- Paradoxical association of higher epinephrine reactivity with lower VTE risk
- Results in this study and among the clinical literature are inconsistent.
- Further studies (e.g., for alternate platelet biomarkers) may be needed.

IntroductionThe relationship of venous thromboembolism (VTE) with platelet reactivity is unclear. Platelet function plays a key role in arterial thrombosis. Evidence suggests antiplatelet agents also effects in reducing VTE. Our aim is to describe the role of baseline platelet function in development of VTE in the community-based Framingham Heart Study (FHS) cohort.Materials and methodsParticipants in the Framingham Offspring cohort fifth examination and Omni cohort first examination were eligible. We used light transmission aggregometry to measure platelet aggregation in response to collagen and a range of ADP and epinephrine doses. The study population consisted of 2831 participants [average age 54.3 years; 57% female].Results and conclusionsDuring a median follow-up of 20.4 years, we observed 138 incident VTE events. In age-, sex- and cohort-adjusted analysis an increase in collagen lag time was associated with increased risk for incident VTE (HR 1.01 [1.00-1.02]; p = 0.049). Increased maximal aggregation to low dose epinephrine (1.0 μM) was associated with lower VTE risk (HR 0.84 [0.71-0.99]; p = 0.042]). However, additional multivariable analyses attenuated the collagen-VTE and epinephrine-VTE associations to trends, primarily due to adjustment for baseline body mass index (BMI), a VTE risk factor and potential modifier of platelet function. Secondary analyses considering varying follow-up periods, cancer incidence and interim aspirin use did not dramatically affect the collagen and epinephrine trends observed. Baseline platelet aggregability was only weakly associated with incident VTE, and in a paradoxical direction, in a community-based population. Other markers of platelet function and hemostasis could prove to be more useful predictors.