Increased procoagulant platelet levels are predictive of death in COVID-19

Abstract

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan–Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2–12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680–1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

“…Anti-PS antibodies correlated with high levels of platelets. Although a low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19 (Lippi et al, 2020), it has also been observed that platelets are hyperactivated during the disease (Zaid et al, 2020) and that immature platelets (Welder et al, 2021) and coated-platelet levels (Khattab et al, 2021) correlate with severity and death in COVID-19 patients, suggesting that they may be involved in thrombo-inflammation and contribute to disease severity.…”

Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation—A Conceptual Review Summarizing Current Knowledge

“…Moreover, since Ca 2+ influxes are important to trigger the procoagulant response, physiological levels of Ca 2+ are required in the medium [ 45 , 46 ]. Nowadays, convulxin/thrombin (COAT) dual agonist stimulation in Ca 2+ buffer—generally recognized as standard—is extensively used by many research groups to assess procoagulant function of platelets [ 3 , 4 , 12 , 22 , 47 , 48 , 49 , 50 , 51 ]. Common model such as procoagulant COAT platelets are required in order to compare observations between research groups [ 51 ].…”

“…This balance seems to be altered in bleeding diatheses [ 6 , 7 ] and hemorrhagic strokes [ 8 , 9 ] where a low procoagulant potential has been observed. On the other hand, in ischemic strokes [ 10 , 11 ] and in conditions as diverse as COVID-19 [ 12 ] and coronary artery disease [ 13 ], a high procoagulant potential was associated with a worse outcome. The clinical implications of procoagulant COAT platelets are addressed in a recent review [ 2 ].…”

Platelets and Antiplatelet Medication in COVID-19-Related Thrombotic Complications

“…However, the impact of COVID-19 on prothrombotic and procoagulatory platelet function is multifaceted, and the underlying molecular mechanisms remain largely obscure. Although high levels of procoagulant fibrinogen-binding platelets, so-called coated platelets, are predictive of death in COVID-19, most patients exhibit lower levels of coated platelets than hospitalized SARS-CoV-2-negative controls ( 24 ). In line, despite the reported association of platelet PS expression with thrombosis and disease severity, the capacity of platelets to respond to stimulation is reduced in COVID-19 ( 25 ).…”