Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation

F. Peyvandi, S. M. Siboni, D. Lambertenghi Deliliers, S. Lavoretano, N. De Fazio, B. Moroni, G. Lambertenghi Deliliers, P. Mannuccio Mannucci

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalBritish Journal of Haematology
Volume134
Issue number2
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Thrombotic Microangiopathies
von Willebrand Factor
Metalloproteases
Bone Marrow Transplantation
Prospective Studies
Thrombotic Thrombocytopenic Purpura
Homologous Transplantation
Plasma Exchange
Incidence
Microcirculation
Thrombosis
Peptide Hydrolases
Blood Platelets
Endothelial Cells
Molecular Weight

Keywords

  • ADAMTS13
  • Bone marrow transplantation
  • Thrombotic microangiopathies
  • Von Willebrand factor

ASJC Scopus subject areas

  • Hematology

Cite this

Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation. / Peyvandi, F.; Siboni, S. M.; Lambertenghi Deliliers, D.; Lavoretano, S.; De Fazio, N.; Moroni, B.; Lambertenghi Deliliers, G.; Mannuccio Mannucci, P.

In: British Journal of Haematology, Vol. 134, No. 2, 07.2006, p. 187-195.

Research output: Contribution to journalArticle

Peyvandi, F. ; Siboni, S. M. ; Lambertenghi Deliliers, D. ; Lavoretano, S. ; De Fazio, N. ; Moroni, B. ; Lambertenghi Deliliers, G. ; Mannuccio Mannucci, P. / Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation. In: British Journal of Haematology. 2006 ; Vol. 134, No. 2. pp. 187-195.
@article{cae763ccd4a2492e883c54d4a6622f48,
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.",
keywords = "ADAMTS13, Bone marrow transplantation, Thrombotic microangiopathies, Von Willebrand factor",
author = "F. Peyvandi and Siboni, {S. M.} and {Lambertenghi Deliliers}, D. and S. Lavoretano and {De Fazio}, N. and B. Moroni and {Lambertenghi Deliliers}, G. and {Mannuccio Mannucci}, P.",
year = "2006",
month = "7",
doi = "10.1111/j.1365-2141.2006.06126.x",
language = "English",
volume = "134",
pages = "187--195",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "2",

}

TY - JOUR

T1 - Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation

AU - Peyvandi, F.

AU - Siboni, S. M.

AU - Lambertenghi Deliliers, D.

AU - Lavoretano, S.

AU - De Fazio, N.

AU - Moroni, B.

AU - Lambertenghi Deliliers, G.

AU - Mannuccio Mannucci, P.

PY - 2006/7

Y1 - 2006/7

N2 - 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.

AB - 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.

KW - ADAMTS13

KW - Bone marrow transplantation

KW - Thrombotic microangiopathies

KW - Von Willebrand factor

UR - http://www.scopus.com/inward/record.url?scp=33745123633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745123633&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2006.06126.x

DO - 10.1111/j.1365-2141.2006.06126.x

M3 - Article

C2 - 16846477

AN - SCOPUS:33745123633

VL - 134

SP - 187

EP - 195

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -