Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms

Aim. We investigated the occurrence and thrombin generating mechanisms of c irculating microparticles (MP) in patients with multiple organ dysfunction syndrome (MODS) and sepsis. Methods. MP, isolated from blood of patients (n = 9) and healthy controls ( n = 14), were stained with cell-specific monoclonal antibodies (MoAbs) or a nti-tissue factor (anti-TF) MoAb and annexin V. and analyzed by flow cytome try. To assess their thrombin-generating capacity. MP were reconstituted in normal plasma. The coagulation activation status in vivo was quantified by plasma prothrombin fragment F1+2- and thrombin-antithrombin (TAT) measurem ents. Results. Annexin V-positive MP in the patients originated predominantly fro m platelets (PMP), and to a lesser extent from erythrocytes. endothelial ce lls (EMP) and granulocytes (GMP). Compared to healthy controls. the numbers of annexin V-positive PMP and TF-exposing MP were decreased (p = <0.001 fo r both). EMP were decreased (E-selectin, p = 0.003) or found equal (CD144, p = 0.063). erythrocyte-derived MP were equal (p = 0.726), and GMP were inc reased (p = 0.008). GMP numbers correlated with plasma concentrations of el astase (r = 0.70, p = 0.036). but not with C-reactive-protein or interleuki n-6 concentrations. Patient samples also contained reduced numbers of annex in V-negative PMP. and increased numbers of erythrocyte-derived MP and GMP (p = 0.005, p = 0.021 and p <less than>0.001, respectively). Patient MP tri ggered thrombin formation, which was reduced compared to the healthy contro ls (p = 0.008) and strongly inhibited by an anti-factor XII MoAb (two patie nts). by anti-factor XI MoAb (eight patients) or by anti-TF MoAb (four pati ents). Concentrations of F,,? and TAT were elevated (p = 0.005 and p = 0.00 1, respectively) and correlated inversely with the number of circulating MP (and r = -0.51. p = 0.013, and r = -0.65, p = 0.001. respectively) and the ir thrombin generation capacity (F1+2: r = -0.62, p = 0.013). Conclusions. In patients with MODS and sepsis relatively low numbers of MP are present that differ from controls in their cellular origin. numbers and coagulation activation mechanisms.