Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation

Abstract

Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis of MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p < 0.05) that correlated with severity of disease (r = 0.597, p = 0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p < 0.05) which well with severity of MOF (GMP-140, r = 0.611, p = 0.013; TSP, r = 0.643, p = 0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

TREM-1 ligand expression on platelets enhances neutrophil activation

“…17,18,21,25 In sepsis, it has been demonstrated that platelets show enhanced adherence to leukocytes 17 and are activated, 18 although the severity only of multiorgan failure, but not of sepsis, correlates with irreversible platelet activation. 26 Under experimental flow conditions, platelets seem to interact preferentially with monocytes rather than PMNs, which are dependent on divalent cations and the expression of PSGL-1 and in part also on ␤1-and ␤2-integrins for fMLP-activated monocytes. 27,28 However, after severe trauma or sepsis, platelets associate significantly with both monocytes as well as PMNs.…”

Changes in the Mean Platelet Volume Levels after Bloodstream Infection Have Prognostic Value

“…Platelet formation from megakaryocytes is an important determinant of the platelet size (21), although to the best of our knowledge, no studies have investigated changes in platelet formation in patients with severe sepsis. The release of platelet granules, another factor influencing the platelet size, was found to be elevated in severely septic patients with multiple organ failure (22), although that study included cardiovascular patients. We assume that changes in the MPV levels may be attributed to a combination of several factors, including decreases in platelet formation by megakaryocytes, platelet consumption in peripheral tissue and degranulation in larger platelets, and that the impact of inflammation on MPV elevation after BSI in nonsurvivors is stronger than that observed in survivors.…”

Platelets and innate immunity

“…Activation of both leukocytes and platelets is commonly observed in sepsis. There is increasing evidence that activation of these cells contributes to the development of disseminated intravascular coagulation (DIC) and multiple organ failure, as blood flow and consequent oxygen delivery is reduced and activation of both pro-and anti-inflammatory cytokine networks are induced [71,74]. CD62P is increased on platelets from septic versus non-septic patients [75,76] and activated platelets release platelet microparticles (MP) that express functional surface receptors that allow them to adhere to leukocytes [76].…”