ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: Implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment

摘要

Background Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective. Study Design and Methods To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA). Results IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products. Conclusion Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 in complex with larger VWF multimers.