Platelet reactivity in sepsis syndrome: results from the PRESS study

Abstract

Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244 ± 66.7 vs 187.33 ± 60.98, p < 0.001 and 192.17 ± 47.51, p < 0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F = 8.836, p < 0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA + PRU, 0.867 vs SOFA, 0.824, p < 0.003 and AUC qSOFA + PRU, 0.842 vs qSOFA, 0.739, p < 0.001), making them comparable (AUC SOFA + PRU vs qSOFA + PRU, p = 0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

“…Platelet reactivity, measured by numerous assays, is increased during acute inflammatory states, for example, sepsis [31]. Platelets themselves are acute phase reactants and inflammation induces thrombocytosis, mediated by an increase in thrombopoetin levels, potentiated by interleukin-6 [32].…”

Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis

“…However, platelet function in sepsis has yielded conflicting data based on previous studies. Human septic platelets have shown increased surface P-selectin expression causing high soluble P-selectin plasma levels [3], elevated thrombospondin exposure [4], and augmented platelet reactivity at early time points of the disease [5]. In contrast, hyporeactive platelets with decreased ex vivo aggregability have been reported in sepsis by others [6,7].…”

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

“…However, it is essential to get further insights on the time course of platelet activation during sepsis, on the consequences of sepsis on platelet prothrombotic properties at arterial shear rate and to evaluate the impact of platelet PI3Kβ inhibition. Only a few studies have investigated platelet activation during sepsis in humans 13 , 23 – 26 or in experimental animal models 27 , 28 . Recently, a study of platelet activation dynamics during the progression of a streptococcus pyogenes infection has proposed that monitoring platelet activation may provide prognostic information in this type of sepsis 29 .…”