Microparticles Are Active Components of Therapeutic Plasma Exchange: Correlation with ADAMTS13 Activity in Patients with Thrombotic Thrombocytopenic Purpura

INTRODUCTION: Therapeutic plasma exchange (TPE) is a widely accepted therapy for TTP. A leading hypothesis for its benefit is that TPE replenishes ADAMTS13 with fresh frozen plasma (FFP) and removes inhibitory antibodies. We have reported that endothelial microparticles (EMP) positive for ULvWF are elevated in acute TTP, decline with repeated TPE, and can inhibit ADAMTS13. Presence of platelet microparticles (PMP) in FFP has been described. This led us to the hypothesis that the benefit of TPE is partly due to its effect on microparticles (MP). We investigated the effect of TPE on MP and ADAMTS13 in TTP. METHODS: Nine patients were studied longitudinally during an episode of TTP. Blood samples were obtained upon admission and daily pre- and post-TPE. Additionally, the infused and removed plasma were studied. EMP defined by CD31+/CD42b− (EMP31), CD62E+ (EMP62) and CD62E+/vWF+ (EMPVWF); PMP were defined by CD31+/CD42b+ (PMP42) and CD41+ (PMP41), all measured in platelet-poor plasma by flow cytometry; concentrations are in millions / mL. ADAMTS13 activity was assayed by a FRETS-vWF73 method of Kokame et al [Br J Haematol2005; 129:93]. vWF multimers were analyzed following Raines et al [Thromb Res1990; 60:201]. RESULTS: At admission, TTP patients exhibited very low ADAMTS13 levels, 0–10% of controls (ctl), and elevated EMP31 (2.5 ±0.7 vs. 0.35 ±0.09 ctl) and EMP62 (6.3 ±1.9 vs. 0.25 ±0.07 ctl), both p CONCLUSION: These results suggest that one action of TPE in TTP is to remove EMP which tend to bind and inactivate ADAMTS13. Thus, the basis of TPE is two-fold: infusion of ADAMTS13 by FFP infusion, and reduction of high levels of inhibitors including inhibitory antibodies as well as EMP.