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Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple
K Joop1, R J Berckmans, R Nieuwland
1Department of Clinical Chemistry, Leiden University Medical Center, The Netherlands.
Aim:
We investigated the occurrence and thrombin generating mechanisms of circulating 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 anti-tissue factor (anti-TF) MoAb and annexin V, and analyzed by flow cytometry. 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) measurements.
Results:
Annexin V-positive MP in the patients originated predominantly from platelets (PMP), and to a lesser extent from erythrocytes, endothelial cells (EMP) and granulocytes (GMP). Compared to healthy controls, the numbers of annexin V-positive PMP and TF-exposing MP were decreased (p = <0.001 for 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 increased (p = 0.008). GMP numbers correlated with plasma concentrations of elastase (r = 0.70, p = 0.036), but not with C-reactive-protein or interleukin-6 concentrations. Patient samples also contained reduced numbers of annexin V-negative PMP, and increased numbers of erythrocyte-derived MP and GMP (p = 0.005, p = 0.021 and p <0.001, respectively). Patient MP triggered thrombin formation, which was reduced compared to the healthy controls (p = 0.008) and strongly inhibited by an anti-factor XII MoAb (two patients), by anti-factor XI MoAb (eight patients) or by anti-TF MoAb (four patients). Concentrations of F1+2 and TAT were elevated (p = 0.005 and p = 0.001, 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 their 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.
Insights
Patients with multiple organ dysfunction syndrome (MODS) and sepsis have fewer circulating microparticles (MP) than healthy individuals. These MP exhibit altered origins and reduced thrombin generation capacity, impacting coagulation activation.
Area of Science:
- Hematology
- Critical Care Medicine
- Coagulation Science
Background:
- Circulating microparticles (MP) are cell-derived vesicles implicated in hemostasis and thrombosis.
- Their role in sepsis and multiple organ dysfunction syndrome (MODS) is complex and not fully understood.
- Investigating MP origin and function is crucial for understanding coagulation dysregulation in critical illness.
Purpose of the Study:
- To investigate the occurrence and thrombin-generating mechanisms of circulating microparticles (MP) in patients with MODS and sepsis.
- To compare MP profiles and coagulation activation markers between patients and healthy controls.
Main Methods:
- MP were isolated from the blood of 9 MODS/sepsis patients and 14 healthy controls.
- Flow cytometry was used to analyze MP stained with cell-specific antibodies, anti-tissue factor (anti-TF), and annexin V.
- Thrombin generation capacity of MP was assessed, and plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin (TAT) were measured.
Main Results:
- Patients exhibited decreased numbers of annexin V-positive platelet-derived MP (PMP) and TF-exposing MP, and decreased endothelial cell-derived MP (EMP).
- Granulocyte-derived MP (GMP) were increased in patients and correlated with elastase levels.
- Patient MP showed reduced thrombin generation capacity, and elevated F1+2 and TAT levels correlated inversely with MP numbers and thrombin generation.
Conclusions:
- Patients with MODS and sepsis have altered circulating MP populations with distinct cellular origins and reduced thrombin generation.
- These findings suggest a complex role for MP in the coagulation abnormalities observed in MODS and sepsis.
- Further research is needed to elucidate the precise mechanisms and clinical implications of these MP alterations.
