The pathogenicity of von Willebrand factor in thrombotic thrombocytopenic purpura: reconsideration of treatment with cryopoor plasma.
New developments in the understanding of thrombotic thrombocytopenic purpura (TTP) provide opportunities for improved patient care. A widely held historical model of TTP microvascular thrombosis implicated circulating ultra large von Willebrand factor (ULVWF) in causing spontaneous platelet (PLT) aggregation. From this pathogenic model, concerns about ULVWF in fresh-frozen plasma (FFP) used to treat patients led to widespread use of cryopoor plasma (CPP) as an alternative. There is scant evidence, however, that circulating ULVWF contributes to microvascular thrombosis in TTP. New evidence suggests that the formation of PLT aggregates in TTP may be mediated by VWF in the process of being released from endothelium. Moreover, clinical studies do not demonstrate superior efficacy of CPP compared to FFP in the treatment of TTP. Because CPP may have reduced concentrations of factors important in the treatment of TTP, including ADAMTS13 metalloprotease, a reappraisal of the use of CPP in the treatment of TTP is warranted.
Raife
Thomas J
TJ
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. thomas-raife@uiowa.edu
Friedman
Kenneth D
KD
Dwyre
Denis M
DM
D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010951:Plasma Exchange; D010974:Platelet Aggregation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human