Platelet Aggregation Alterations in Patients with Severe Viral Infection Treated at the Intensive Care Unit: Implications for Mortality Risk

Abstract

Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis (p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.

Keywords: ARDS; COVID-19; ECMO; intensive care; platelet aggregation; platelet desensitization; viral sepsis.

Figure 1

Graphs comparing platelet receptor activity between survivors and nonsurvivors on days 1, 3, and 5 of ECMO treatment. Dotted lines represent the lower and upper reference ranges for each test: ASPI 745–1361 AU/min (A), ADP 534–1220 AU/min (B), TRAP 941–1536 AU/min (C), RISTO 896–2013 AU/min (D). The p-values represent differences between the study groups at each time point. The box plots represent the median values (middle line) with upper and lower quartiles (box); the whiskers represent the minimum and maximum values.

Figure 1

Graphs comparing platelet receptor activity between survivors and nonsurvivors on days 1, 3, and 5 of ECMO treatment. Dotted lines represent the lower and upper reference ranges for each test: ASPI 745–1361 AU/min (A), ADP 534–1220 AU/min (B), TRAP 941–1536 AU/min (C), RISTO 896–2013 AU/min (D). The p-values represent differences between the study groups at each time point. The box plots represent the median values (middle line) with upper and lower quartiles (box); the whiskers represent the minimum and maximum values.

Figure 2

Kaplan–Meier curves stratified by the presence of platelet aggregation results recorded on day 1 in all tests (ASPI, ADP, TRAP, and RISTO) below vs. within the reference range (log-rank test).

Figure 3

ROC curve statistics for aggregometry results measured on day 1 as predictors of ICU mortality. AUC, area under the curve.