title: Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance.
abstract: BACKGROUND
  Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability.
  
  
  METHODS
  Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability.
  
  
  RESULTS
  A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38.
  
  
  CONCLUSIONS
  Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.
authors.affiliation: Saint Barnabas Medical Center, Department of Transplantation, Livingston, New Jersey 07039, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Friedman
authors.forename: D
authors.initials: D
authors.lastname: Wik
authors.forename: L
authors.initials: L
authors.lastname: Silva
authors.forename: J C
authors.initials: JC
authors.lastname: Abdou
authors.forename: H U
authors.initials: HU
authors.lastname: Meier-Kriesche
authors.forename: B
authors.initials: B
authors.lastname: Kaplan
authors.forename: L
authors.initials: L
authors.lastname: Bonomini
authors.forename: P
authors.initials: P
authors.lastname: DeFranco
authors.forename: N
authors.initials: N
authors.lastname: Lyman
authors.forename: S
authors.initials: S
authors.lastname: Mulgaonkar
authors.forename: M
authors.initials: M
authors.lastname: Jacobs
mesh_terms: D000017:ABO Blood-Group System; D020016:Activated Protein C Resistance / Q000150:complications* / Q000276:immunology; D000328:Adult; D015331:Cohort Studies; D015897:Comorbidity; D000795:Fabry Disease / Q000150:complications* / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis; D015796:HLA-B27 Antigen / Q000032:analysis; D059945:HLA-B38 Antigen; D015795:HLA-B8 Antigen / Q000032:analysis; D015803:HLA-DR3 Antigen / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D017211:Treatment Failure; D044465:White People
chemical_list: D000017:ABO Blood-Group System; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D059945:HLA-B38 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen