Vascular antithrombin and clinical outcome in heart transplant patients

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 con secutive 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 c apillaries, of all donor heart biopsy samples. Allografts that maintained v ascular antithrombin had the best prognosis. Allografts with early and pers istent loss of vascular antithrombin (n = 21) developed CAD earlier (p < 0. 001), developed more severe disease (p < 0.001), showed more disease progre ssion (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), an d failed less often (p = 0.01) and later (p = 0.03) than allografts with pe rsistent loss of vascular antithrombin. The persistent lock of a thrombores istant microvasculature increases risk of subsequent CAD and graft failure. However, recovery of vascular antithrombin and development of unusual capi llary antithrombin binding improves allograft outcome. (C) 2001 by Excerpta Medico, Inc.