Decreased Threshold of Aggregation to Low-Dose Epinephrine is Evidence of Platelet Hyperaggregability in Patients with Thrombosis

Abstract

Sticky platelet syndrome has been described as a hereditary thrombophilic condition. The aim of this study is to identify the presence of platelet hyperaggregability in patients who have experienced thrombosis. Light-transmittance platelet aggregometry was used to assess for spontaneous platelet aggregation, aggregation in response to full and low-dose (LD) epinephrine (Epi) and adenosine diphosphate, as well as arachidonic acid, and identify a distinct pattern of platelet hyperaggregability. Light-transmittance platelet aggregometry results were correlated with PFA-100® (Dade-Behring, Marburg, Germany) results, when available. An exaggerated response to LD Epi was found in 68% of patients with thrombosis compared to only 36% of healthy controls (P=0.034). Patients with thrombosis, either arterial or venous, demonstrated an exaggerated response to LD Epi nearly twice as frequently as healthy controls, even without significant family history of thrombophilia or other known risk factors for thrombosis. This suggests that platelet hyperaggregability may be multifactorial in nature and not necessarily hereditary.

Platelet function as a risk factor for venous thromboembolism in the Framingham Heart Study

“…The association of platelet aggregability with VTE was studied cross-sectionally in 63 patients with a history of VTE, with a control sample of 14 healthy volunteers. [8] In the study patients with arterial events (n=31) were further combined in analysis with VTE patients for a total of 94 samples. Light transmission aggregometry with normal and low-dose epinephrine or ADP as well as spontaneous aggregation were recorded within a few weeks after venous or arterial thrombosis.…”

“…No association with ADP or arachidonic acid was reported by Hayes et al, and responses to collagen were not measured. [8]…”

“…However, higher percent aggregation to low dose collagen (0.05 u M) was associated VTE (P=0.00076), as was higher aggregation to low dose TRAP-6 (2.0 u M) (P=0.006). In our current study we did not have data available to evaluate thrombin or low dose collagen effects in order to compare to the results of Weber et al [9], and these pathways of activation were not evaluated by Hayes et al [8]…”

“…Inclusion criteria adopted in many of these studies focusing on unexplained thrombosis or cases without family history of thromboembolic events, or bleeding or coagulation disorders, differs significantly from our population-based study. Hayes et al [8] and many of the SPS [17] studies conducted dichotomized threshold tests for ADP and epinephrine whereas most of our analyses focused on continuous trait data. Some studies have combined arterial and venous events in their analysis, making it possible that their findings were driven in part by associations with arterial events.…”

“…[6,7] Several small studies have variously reported an exaggerated platelet aggregation response to epinephrine, collagen or thrombin in patients with thrombosis but have not been completely consistent. [8,9] However, to our knowledge, no studies on platelet aggregation measures as prospective predictors of VTE risk have been published to date. Our aim is to describe the role of platelet function at baseline in the development of VTE in the community-based Framingham Heart Study (FHS) cohort.…”