title: Vascular antithrombin and clinical outcome in heart transplant patients.
abstract: A procoagulant microvasculature is associated with accelerated development of coronary artery disease (CAD) and failure in heart transplant patients. This study was performed to evaluate how changes in natural anticoagulation within cardiac allografts affect outcome. We prospectively studied 141 consecutive cardiac allograft recipients who underwent transplantation between 1988 and 1997. Serial endomyocardial biopsy specimens (6.5 +/- 0.1 biopsy specimens/patient) obtained during the first 3 months after transplantation were studied immunohistochemically to evaluate vascular antithrombin, and annual coronary angiograms (3.8 +/- 0.2 angiograms/patient) were studied to evaluate CAD. Antithrombin was present in arteries and veins, but not in capillaries, of all donor heart biopsy samples. Allografts that maintained vascular antithrombin had the best prognosis. Allografts with early and persistent loss of vascular antithrombin (n = 21) developed CAD earlier (p < 0.001), developed more severe disease (p < 0.001), showed more disease progression (p < 0.001), and failed more often (p = 0.003) and earlier (p < 0.001) than allografts retaining normal vascular antithrombin (n = 45). However, allografts that lost and recovered vascular antithrombin while developing unusual capillary antithrombin binding (n = 75) had less CAD, developed CAD later, had less severe disease and less disease progression (p < 0.01), and failed less often (p = 0.01) and later (p = 0.03) than allografts with persistent loss of vascular antithrombin. The persistent lack of a thromboresistant microvasculature increases risk of subsequent CAD and graft failure. However, recovery of vascular antithrombin and development of unusual capillary antithrombin binding improves allograft outcome.
authors.affiliation: Methodist Research Institute, Methodist Transplant Center,  Indiana University, Riley Hospitals, Indianapolis 46202, USA. clabarrere@clarian.com
authors.forename: C A
authors.initials: CA
authors.lastname: Labarrere
authors.forename: R J
authors.initials: RJ
authors.lastname: Torry
authors.forename: D R
authors.initials: DR
authors.lastname: Nelson
authors.forename: S J
authors.initials: SJ
authors.lastname: Miller
authors.forename: D E
authors.initials: DE
authors.lastname: Pitts
authors.forename: P C
authors.initials: PC
authors.lastname: Kirlin
authors.forename: H G
authors.initials: HG
authors.lastname: Halbrook
mesh_terms: D000991:Antithrombins / Q000378:metabolism*; D001706:Biopsy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000209:etiology; D006084:Graft Rejection / Q000209:etiology; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins