title: Prophylactic fresh frozen plasma may prevent development of hepatic VOD after stem cell transplantation via ADAMTS13-mediated restoration of von Willebrand factor plasma levels.
abstract: We initially conducted a multicenter, randomized trial (n=43), and subsequently a questionnaire study (n=209) of participating hospitals, to evaluate whether infused fresh frozen plasma (FFP) could prevent the occurrence of hepatic veno-occlusive disease (VOD) after stem cell transplantation (SCT). Forty-three patients were divided into two groups: 23 receiving FFP infusions and 20 not receiving it. VOD developed in three patients not receiving FFP. Plasma von Willebrand factor (VWF) antigen levels were lower at days 0, 7 and 28 after SCT in patients receiving FFP than in those not receiving it, whereas plasma ADAMTS13 activity (ADAMTS13:AC) did not differ between them. Plasma VWF multimer (VWFM) was demonstrated to be defective in the high approximately intermediate VWFM during the early post-SCT phase, but there was a significant increase in high VWFM just before VOD onset. This suggests that a relative enzyme-to-substrate (ADAMTS13/high-VWFM) imbalance is involved in the pathogenesis of VOD. To strengthen this hypothesis, the incidence of VOD was apparently lower in patients receiving FFP infusions than in those not receiving it (0/23 vs 3/20) in the randomized trial. Further, the results combined with the subsequent questionnaire study (0/36 vs 11/173) clearly showed the incidence to be statistically significant (0/59 vs 14/193, P=0.033).
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Kawa
authors.forename: M
authors.initials: M
authors.lastname: Uemura
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Ishizashi
authors.forename: A
authors.initials: A
authors.lastname: Isonishi
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: Y-D
authors.initials: YD
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Y
authors.initials: Y
authors.lastname: Kosaka
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Kai
authors.forename: A
authors.initials: A
authors.lastname: Kanamaru
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
authors.forename: M
authors.initials: M
authors.lastname: Hino
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: A
authors.initials: A
authors.lastname: Hiraoka
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
authors.forename: J
authors.initials: J
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000473:pathology / Q000628:therapy; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000201:enzymology; D033581:Stem Cell Transplantation; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human