Increased platelet count and reticulated platelets in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic signal-negative patient subgroups: results from the HaEmostasis In carotid STenosis (HEIST) study

The pathophysiological mechanisms responsible for the disparity in stroke risk between asymptomatic and symptomatic carotid stenosis patients are not fully understood. The functionally important reticulated platelet fraction and reticulocytes could play a role. We performed a prospective, multi-centre, observational analytical study comparing full blood count parameters and platelet production/turnover/activation markers in patients with asymptomatic versus recently symptomatic moderate (50-69%) or severe (70-99%) carotid stenosis. Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (4 weeks) and 37 of these patients in the 'late phase' (3 months) after TIA/ischaemic stroke. Reticulated platelets were quantified by whole blood flow cytometry and reticulated platelets and red cell reticulocytes by 'automated assays' (Sysmex XE-2100 (TM)). Bilateral simultaneous transcranial Doppler ultrasound monitoring classified patients as micro-embolic signal (MES)+ve or MES-ve. Mean platelet count was higher in early (216 x 10(9)/L; P = 0.04) and late symptomatic (219 x 10(9)/L; P = 0.044) than asymptomatic patients (194 x 10(9)/L). Mean platelet volume was higher in early symptomatic than asymptomatic patients (10.8 vs. 10.45 fl; P = 0.045). Automated assays revealed higher % reticulated platelet fractions in early (5.78%; P < 0.001) and late symptomatic (5.11%; P = 0.01) than asymptomatic patients (3.48%). Red cell reticulocyte counts were lower in early (0.92%; P = 0.035) and late symptomatic (0.93%; P = 0.036) than asymptomatic patients (1.07%). The automated % reticulated platelet fraction was also higher in early symptomatic than asymptomatic MES-ve patients (5.7 vs. 3.55%; P = 0.001). The combination of increased platelet counts and a shift towards production of an increased population of larger, young, reticulated platelets could contribute to a higher risk of first or recurrent cerebrovascular events in recently symptomatic versus asymptomatic carotid stenosis, including those who are MES-ve.