title: Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation.
abstract: BACKGROUND
  Hemostatic events in patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) increase the morbidity and mortality in this cohort. Little is known about the impact of graft-versus-host disease (GvHD) or of thrombophilic gene mutations/polymorphisms on these complications.
  
  
  METHODS
  Eighty-nine allogeneic stem-cell recipients and their donors were evaluated prospectively for the presence of the factor V G1691A mutation, the prothrombin G20210A mutation, the 5,10-methylenetetrahydrofolate-reductase (MTHFR) C677T mutation, the glycoprotein IIIa PI(a1/a2) polymorphism, the fibrinogen-beta-chain 455G/A polymorphism, the plasminogen activator inhibitor-1 -675 4G/5G polymorphism, and the angiotensin-converting enzyme intron 16 I/D polymorphism. These mutations/polymorphisms and GvHD parameters were correlated to hemostatic and toxic complications after transplantation. The data were compared with those of 128 healthy controls.
  
  
  RESULTS
  The PAI-1 4G/4G polymorphism increases the risk for catheter thrombosis after HSCT 5.7-fold (32.2% vs. 71.4%, P<0.05). In patients with hepatic veno-occlusive disease, the frequency of the PAI-1 4G allele is also increased (83.3% vs. 55.1%, NS). Thrombophilic mutations/polymorphisms in donors do not influence complications in the corresponding recipients. The MTHFR TT genotype does not modify severity and duration of mucositis and aplasia in patients receiving methotrexate prophylaxis. Patients with chronic GvHD have a higher risk of thromboembolism (12.9% vs. 1.7%, P<0.05).
  
  
  CONCLUSIONS
  Thrombophilic gene mutations have only a moderate influence on hemostatic complications in patients undergoing HSCT. This may be because of the overwhelming immunologic impact of GvHD on hemostasis in the allogeneic transplantation setting.
authors.affiliation: Abteilung fuer Haematologie und Internistische Onkologie, Klinikum der Universitaet Regensburg, Regensburg, Germany. Markus.Pihusch@t-online.de
authors.forename: Markus
authors.initials: M
authors.lastname: Pihusch
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Jill
authors.initials: J
authors.lastname: Reitberger
authors.forename: Erhard
authors.initials: E
authors.lastname: Hiller
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Rudolf
authors.initials: R
authors.lastname: Pihusch
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013923:Thromboembolism / Q000453:epidemiology* / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)