Abstract Number: PB1701
Meeting: ISTH 2020 Congress
Background: Sepsis is the leading cause of death at intensive care units (ICU) worldwide. During sepsis, patients frequently suffer from disseminated bleeding and thrombosis events as a consequence of hemorrhagic diathesis and edema formation due to loss of vascular integrity. Hemostasis and the maintenance of vascular integrity mainly depend on the function of platelet immunoreceptors including the immunoreceptor tyrosine activation motif (ITAM) receptor glycoprotein GPVI rather than on the mere platelet count. Thrombocytopenia during sepsis has been closely investigated and is a diagnostic criterium. Platelet function, in contrast, remains ill-defined due to few studies with overall contradictory results.
Aims: We assessed platelet function and immunoreceptor signaling longitudinally over the course of sepsis.
Methods: Blood withdrawal was scheduled for three time points (t1) ICU admission day; (t2) day five to seven; (t3) ICU discharge. Platelet activation was determined in 15 patients with sepsis by flow cytometry indicated by P-selectin exposure and integrin GPIIb/IIIa activation. Light transmission aggregometry (LTA) was performed with washed platelets (500/nl). ITAM signaling cascades were assessed by immunoblot and ELISA.
Results: We found unaltered platelet receptor expression, but markedly reduced reactivity to various agonists (for all patients), assessed by flow cytometry and LTA. This defect was most prominent after GPVI stimulation with collagen-related peptide (Mean Geo-MFI ± SD; Control: 9356 ± 3460; Sepsis: 1438 ± 2090; p< 0.0001). In 14/15 patients GPVI-dysfunction was already present at ICU admission, considerably before the critical drop in platelet counts. Sepsis platelets failed to transduce the GPVI-mediated signal to induce tyrosine phosphorylation of Syk kinase or LAT. Platelet aggregation upon GPVI stimulation increased only in those patients whose condition ameliorated. We found a strong correlation (r=0.63; p< 0.01) of restored platelet aggregation with patient survival.
Conclusions: GPVI dysfunction is a bona fide indicator for early sepsis diagnosis while restored GPVI function clearly indicates patient recovery and survival.
To cite this abstract in AMA style:Weiss LJ, Manukjan G, Nagler N, Kredel M, Lâm T-, Nieswandt B, Weismann D, Schulze H. Acquired GPVI Deficiency Is a Biomarker for Early Diagnosis and Prognostic Assessment of Patients with Sepsis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/acquired-gpvi-deficiency-is-a-biomarker-for-early-diagnosis-and-prognostic-assessment-of-patients-with-sepsis/. Accessed January 26, 2022.
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