Sepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study

Abstract

BackgroundPlatelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients.MethodsThis single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48 h later, and then at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded.MethodsOf the 99 patients, 19 developed sepsis after a median time of 5 days. These patients had a higher SOFA score at admission; levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were also significantly increased compared to the other patients. Levels 48 h after ICU admission no longer differed between the two patient groups. Platelet-Fg % was an independent predictor of sepsis (P = 0.0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was 50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and hospital stays and higher death rate.ConclusionsPlatelet-bound fibrinogen levels assayed by flow cytometry within 24 h of ICU admission help identifying critically ill patients at risk of developing sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0145-2) contains supplementary material, which is available to authorized users.

Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis

“…There was also a significant decrease in CD34 + platelets, which is suggestive of platelet activation, although platelet clusters, another sign of platelet activation, was not increased in sepsis patients 50 . Interestingly, this unique phenotype lacking platelet aggregation but having an increase in platelet activation is consistent with previous research demonstrating that platelets from patients with sepsis are more likely to spontaneously activate but are less likely to aggregate in response to various platelet agonists [51][52][53][54] . This platelet phenotype was also observed to revert to 'normal' over time as a patient was treated for sepsis, suggesting that this may also be an early indicator of sepsis.…”

Fibrinogen – A Practical and Cost Efficient Biomarker for Detecting Periprosthetic Joint Infection

“…In the literature, fibrinogen has proven to be a useful progress and/or prediction marker for a variety of inflammation-related pathologies including appendicitis 25 , periodontitis 26 , malaria 27 and sepsis 28 . In this context, the aim of this study was to analyze the plasma concentrations of fibrinogen with respect to its sensitivity and specificity in detecting bacterial joint infections in the field of RTKA and RTHA.…”

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

“…49,50 Evidence suggests a prominent role for inappropriate platelet activation and aggregation during sepsis, 51 and platelet indices beyond platelet count are useful to evaluate illness severity and prospectively identify critically ill patients. 52,53 In this regard, sGPVI represents an excellent candidate marker of pathological platelet activation in the setting of sepsis, as it is a platelet/megakaryocytespecific membrane protein that is stable on circulating platelets but released on ligand engagement of ITAM receptors, exposure to FXa, or abnormal fluid shear rates. 54 sGPVI levels are not elevated as a consequence of ablated platelet production.…”