Platelet responsiveness in the post-acute phase of pulmonary embolism

Introduction Enhanced platelet activity is associated with an increased risk of venous thromboembolism, in particular acute pulmonary embolism (PE) and less so for deep vein thrombosis. This study aimed to investigate platelet function during and after partial cessation of antithrombotic therapies in the post-acute stage of PE.

Method A subgroup of 206 confirmed PE patients from the GMP-VTE project (Genotyping and Molecular Phenotyping of Venous ThromboEmbolism), a multicenter prospective cohort study of 693 confirmed VTE cases, was analyzed. Platelet fibrinogen binding, CD62P, CD63 surface expression and procoagulant activity (annexin-V) were assessed in citrated whole blood by flow cytometry as well as PFA-200; light transmission platelet aggregometry (LTA) and calibrated automated thrombinography (CAT) capacity were assessed in platelet-rich plasma at the acute PE event (BL) and at follow-up at 3/6, 12, and 24 months. Repeated-measures ANOVA was used to examine changes over time, and paired t tests were used for comparisons between time points (e.g., Δt1-t0).

Results Within the follow-up period the percentage of anticoagulant users declined (BL: 84.2%; 12 months: 72.8%; 24 months: 35.9%). In contrast, antiplatelet therapy was stopped immediately after confirmation of PE in most cases (BL: 37%; 3/6 months: 11.1%). Ex vivo platelet fibrinogen-binding (Δ12m-BL=-11%, p<0.0001), tissue factor (Δ12m-BL=-12%, p=0.028) and CD63 (Δ12m-BL=-3%, p<0.0001) surface expression were stably downregulated after 12 months independent of antiplatelet and anticoagulant therapies. In comparison, the PFA coll/epi but not the coll/ADP closure times showed a stable shortening at 3/6 months follow-up (Δ3/6m-BL=-35 sec, p=0.0033) independent of anticoagulant therapy. However, reduced levels of CD63-positive platelets and shortened PFA closure time were still within established normal reference ranges. Impaired arachidonic acid-induced platelet aggregation in the acute phase had increased after 3/6-month follow-up for non-antiplatelet drug users (Δ3/6m-BL=+17%, p=0,0021). Impaired collagen-induced platelet aggregation (Δ3/6m-BL=+18%, p<0.0001) and tissue factor-triggered endogenous thrombin potential (ETP) (Δ3/6m-BL=+696nM*min, p=0.015) in the acute phase had normalized at 3/6-months follow-up for non-antiplatelet drug and non-anticoagulant users, respectively.

Conclusion Platelet activation and reactivity are impaired in acute PE and recover over a period of 3 to 12 months after the acute event. Both antiplatelet and anticoagulant therapies are associated with platelet hypo-reactivity in post-acute PE.

Publication History

Article published online:
20 February 2023