Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

Abstract

BackgroundSickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and MethodsIn the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. ResultsThe majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=-0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). ConclusionsWe conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles.Key words: microparticles, sickle cell disease, coagulation activation, hemolysis. Citation

Robust Label-free, Quantitative Profiling of Circulating Plasma Microparticle (MP) Associated Proteins

“…4). In fact, higher concentrations of erythrocyte-derived MP would probably indicate hemolysis of blood during the preanalytical preparation of PFP, or a disease like sickle cell disease (32). Platelet-derived MP are known to be the most abundant population (33,34) and clearly confirmed by our profiling data (Fig.…”

Hypercoagulability and thrombotic complications in hemolytic anemias

“…33 In their study published in this issue of the Journal, van Beers and colleagues report that the majority of microparticles in SCD patients originate from platelets and erythrocytes, and that the numbers of these microparticles do not differ significantly between crisis and steady state. 34 Unlike a previous study by Shet and colleagues, 17 no microparticles originating from monocytes or endothelial cells were detectable and no microparticles expressing tissue factor were identified. Erythrocyte-derived microparticles correlated strongly with plasma levels of hemolytic markers, as well as to von Willebrand factor, D-dimer and F1+2 levels.…”

Excess of heme induces tissue factor-dependent activation of coagulation in mice

“…30 Platelet-and erythrocyte-derived MPs, which are TF negative, contribute to thrombin generation in a FXII/FXI-dependent manner, whereas thrombin generation induced by TF-positive leukocyte-derived MPs requires FVII but not FXII. 32,33 In our dose titration and time course experiment, we did not observe any increase in the total number of PS-positive MPs at 1, 3 or 6 h after heme treatment (data not shown), which may explain the lack of FXI contribution to the heme-induced activation of coagulation. Furthermore, it is unlikely that increased levels of free heme can lead to the activation of FXII because treatment of heme-injected mice with 14E11 antibody (an inhibitor of FXIIa-mediated activation of FXI), had no effect on plasma TAT levels.…”