title: Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation.
abstract: Thrombotic microangiopathies (TMAs) are rare but serious complications of bone marrow transplantation (BMT). Clinical manifestations are similar to those of thrombotic thrombocytopenic purpura (TTP), but prognosis is generally poorer despite plasma exchange. The enzymatic activity of the plasma metalloprotease ADAMTS13, which cleaves ultralarge thrombogenic multimers of von Willebrand factor (VWF) derived from activated endothelial cells, is very low or undetectable in patients with classic TTP, and protease deficiency is thought to play a mechanistic role in the formation of platelet thrombi in the microcirculation. This is the first prospective study to evaluate the incidence of TMA in 46 consecutively recruited patients undergoing autologous or allogeneic BMT and explore in parallel the behaviour of ADAMTS13, VWF antigen and VWF multimer size. The incidence of post-BMT TMA was 6% (three of 46); all cases occurred after allogeneic BMT. Compared with baseline values plasma ADAMTS13 activity was significantly reduced in patients undergoing BMT, particularly after the conditioning regimen (mean values: 50 +/- 22 vs. 77 +/- 32%; P < 0.0001). In the three patients who developed TMA, ADAMTS13 decreased after conditioning, but was very low in one case only (8%). VWF antigen levels progressively increased after the conditioning regimen (228 +/- 75 vs. 178 +/- 76% at baseline, P = 0.002). The mean proportion of high-molecular weight VWF multimers did not change in the various stages of BMT, even though ultralarge multimers were transiently found in same cases with and without TMA. Hence, the measurements evaluated in this study are not clinically useful to predict the occurrence of post-BMT TMA.
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, University of Milan, Luigi Villa Foundation, Department of Medicine and Medical Specialities, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.forename: S M
authors.initials: SM
authors.lastname: Siboni
authors.forename: D
authors.initials: D
authors.lastname: Lambertenghi Deliliers
authors.forename: S
authors.initials: S
authors.lastname: Lavoretano
authors.forename: N
authors.initials: N
authors.lastname: De Fazio
authors.forename: B
authors.initials: B
authors.lastname: Moroni
authors.forename: G
authors.initials: G
authors.lastname: Lambertenghi Deliliers
authors.forename: P
authors.initials: P
authors.lastname: Mannuccio Mannucci
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000209:etiology*; D019172:Transplantation Conditioning; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human