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

Abstract

Coronavirus disease 2019 (COVID-19) induces a hypercoagulatory state that frequently leads to thromboembolic complications. Whereas anticoagulation is associated with reduced mortality, the role of antiplatelet therapy in COVID-19 is less clear. We retrospectively analyzed the effect of anticoagulation and antiplatelet therapy in 578 hospitalized patients with COVID-19 and prospectively monitored 110 patients for circulating microthrombi and plasma markers of coagulation in the first week of admission. Moreover, we determined platelet shape change and also thrombi in postmortem lung biopsies in a subset of patients with COVID-19. We observed no association of antiplatelet therapy with COVID-19 survival. Adverse outcome in COVID-19 was associated with increased activation of the coagulation cascade, whereas circulating microthrombi did not increase in aggravated disease. This was in line with analysis of postmortem lung biopsies of patients with COVID-19, which revealed generally fibrin(ogen)-rich and platelet-low thrombi. Platelet spreading was normal in severe COVID-19 cases; however, plasma from patients with COVID-19 mediated an outcome-dependent inhibitory effect on naïve platelets. Antiplatelet medication disproportionally exacerbated this platelet impairment in plasma of patients with fatal outcome. Taken together, this study shows that unfavorable outcome in COVID-19 is associated with a profound dysregulation of the coagulation system, whereas the contribution of platelets to thrombotic complications is less clear. Adverse outcome may be associated with impaired platelet function or platelet exhaustion. In line, antiplatelet therapy was not associated with beneficial outcome.

Breakthrough infections after COVID-19 vaccinations do not elicit platelet hyperactivation and are associated with high platelet–lymphocyte and low platelet–neutrophil aggregates

“…To determine if the circulating platelets of patients with COVID-19 could form pathological platelet–platelet aggregates in vivo, we quantified directly in whole blood the CD41a+ events that were larger than regular platelets but did not bind leukocytes, previously described as circulating microthrombi [ 15 , 16 ]. Platelet–platelet aggregates were detected in the blood of unvaccinated COVID-19, most frequently in patients admitted to the ICU, but not in vaccinated patients with COVID-19 (fold change non-ICU: 2.3 ± 2.6; ICU: 3.5 ± 4.1; vaccinated: 0.9 ± 1.0) ( Figure 4 A).…”

The impact of platelets on pulmonary microcirculation throughout COVID-19 and its persistent activating factors

“…As for the controversies about the efficacy of antiplatelet drugs, different conclusions may be drawn based on the bias in clinical trials, such as patients with different disease severity, the phase and duration of drug use, combinations of other drugs, diverse primary outcomes, and so on ( Table 1 ). Analysis of a retrospective study showed no association of antiplatelet therapy (aspirin and/or P2Y 12 receptor antagonists) with survival in hospitalized patients with COVID-19 ( 119 ). In a randomized controlled study, in-hospital antiplatelet therapy was less likely to improve organ support-free days within 21 days in critically ill patients, but it improved the probability of survival to discharge (97%) and survival over 90 days (99.7%) ( 120 ).…”

Complications of COVID-19 and possible role of angiotensin converting enzyme inhibitors and anti-platelet medications in lowering the risk of COVID -19 infection

“…COVID-19 induced hypercoagulatory state that frequently leads to thromboembolic complications, whereas anticoagulation is associated with reduced mortality and role of anti-platelet therapy is very less clear [17]. It is very evident that anti-platelet therapy might be effective in improving the ventilation in COVID-19 patients with severe respiratory failure.…”

“…The hypercoagulatory state induced in COVID-19 shows clinical and laboratory features with partially overlapped bacterial sepsis induced coagulopathy (SIC) but represents a unique condition that has been termed "COVID Associated Coagulopathy" (CAC) [24] which is characterized by wide spread deregulation coagulation parameters such as D-dimer, prolonged prothrombin time and slight reduction in platelet count [25]. The precise mechanism of COVID Associated Coagulopathy (CAC) is under investigation and seems very complexed due to several patho-physiological environmental conditions created by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection which is influenced by plethora of mediators [17]. Immunothrombosis represents crucial link with hypercoagulability, endothelial dysfunction, severe respiratory failure wherein neutrophils, platelets are dysregulated in coagulation cascade work [26][27][28].…”