title: Predictive markers for hepatic veno-occlusive disease after hematopoietic stem cell transplantation in adults: a prospective single center study.
abstract: Hepatic veno-occlusive disease (VOD) is a major complication after hematopoietic stem cell transplantation (HSCT). Aetiological determinants, diagnosis and treatment remain unclear. Changes in coagulation-fibrinolysis parameters and N-terminal propeptide for type III procollagen (P-III-P) have been studied in patients with or without VOD after HSCT. We prospectively measured protein C activity, tissue plasminogen activator (t-PA), antithrombin III (AT-III), plasminogen activity (PLG), thrombin-antithrombin III (TAT), alpha2-plasmin inhibitor (alpha2-PI),fibrinogen (Fbg) and P-III-P in 44 consecutive adult patients undergoing allogeneic HSCT. Each parameter was determined before conditioning, on day 0 of HSCT and weekly for 5 weeks. Five of the 44 patients developed VOD at a median post HSCT of day 3 (range, day 3 to 12). On repeated analysis of variance (ANOVA), there were significant differences between patients with and without VOD in P-III-P (P < 0.0001), protein C (P < 0.0001), t-PA (P < 0.0001), PLG (P < 0.0001), AT-III(P < 0.0001), Fbg (P < 0.0001), alpha2-PI (P = 0.0002). Levels of P-III-P were significantly higher in patients with VOD than without VOD, before preparative chemotherapy (P < 0.005) and on days 0 and 7 (P < 0.001). On day 0, levels of t-PA were significantly higher in patients with VOD than without VOD (P < 0.05). On day 7, levels of protein C were significantly lower in patients with VOD than without VOD (P < 0.01). On day 0, there were trends of differences (P = 0.0515) between patients with and without VOD in the levels of protein C. These results suggest P-III-P, t-PA and protein C are predictive markers for VOD after HSCT in adults. Moreover, the serum P-III-P level before start of conditioning might indicate patients at risk for developing VOD.
authors.affiliation: Bone Marrow Transplantation Team, Tokyo Metropolitan Komagome Hospital, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tanikawa
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Ohhashi
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Kaku
authors.forename: K
authors.initials: K
authors.lastname: Hiruma
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: H
authors.initials: H
authors.lastname: Sakamaki
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000032:analysis
chemical_list: D010446:Peptide Fragments; D011347:Procollagen; D011486:Protein C; C041876:procollagen Type III-N-terminal peptide; D010959:Tissue Plasminogen Activator