Comparison of von Willebrand factor antigen, von Willebrand factor‐cleaving protease and protein S in blood components used for treatment of thrombotic thrombocytopenic purpura

Abstract

Replacement of normal levels of von Willebrand factor-cleaving protease (VWF:CP, ADAMTS13) activity from infused plasma is important in plasma exchange (PEX) for the treatment of thrombotic thrombocytopenic purpura (TTP) patients. We have studied the VWF:CP activity, VWF multimer distribution, VWF:Ag, protein S (PS) activity and free PS antigen levels in fresh frozen plasma (FFP), cryosupernatant (CSP) and virally inactivated components treated with methylene blue/light (MB) or solvent detergent (SD) processes. VWF:CP activity was normal in all components tested and was retained following overnight storage at room temperature. CSP and SD plasma contained reduced levels of the highest molecular weight VWF multimers. Protein S activity was reduced below the normal range in SD plasma, but within the normal range for the other components tested. Virally inactivated SD- and MB-treated plasma may be an effective alternative to FFP and CSP in PEX for TTP. Reduced PS activity in SD plasma may predispose to venous thromboembolism, especially if infused in large volumes.

A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

“…10,11 ADAMTS13 activity was expressed as a percentage relative to the activity in pooled normal plasma (normal range 55%-126%; lower limit of detection 5%).…”

Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency

“…However, large VWF multimers may continue to derive from endothelial cells, and cryoprecipitate-depleted plasma is comparable to fresh frozen plasma in the ADAMTS13 activity level [83][84][85]. Two small randomized controlled trials have failed to demonstrate that the use of cryoprecipitate-depleted plasma is superior to fresh frozen plasma as initial replacement therapy [86;87].…”

“…The ADAMTS13 activity levels have been investigated in a variety of plasma products [83][84][85]. Levels comparable to that in fresh frozen plasma are present in various plasma fractions and some of its derived products.…”

Thrombin Generation Capacity of Methylene Blue-Treated Plasma Prepared by the Theraflex MB Plasma System

“…Garwood et al [6] have shown that, although a freeze-thaw step has little effect on fibrinogen and FVIII levels, losses due to MB treatment are 5-10% lower in fresh plasma compared to frozenthawed plasma. Other plasma factors like von WillebrandFactor, ADAMTS 13, AT, protein C and protein S, however, are only slightly or not at all affected [3,[7][8][9]]. The decrease in the level of fibrinogen is seen by the Clauss assay, but not in the antigen assay [9].…”