Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy

Background-Transplant vasculopathy is the main limiting factor of the long- term success of heart transplantation. We sought to establish the role of p latelets in the development and progression of transplant vasculopathy, Methods and Results-Platelet analysis and intracoronary ultrasound examinat ion were performed in 78 heart transplant recipients. Quantitative intracor onary ultrasound was used to define the severity of disease at baseline (48 .8+/-4.5 months after transplantation) and at 1-year follow-up. Platelet ac tivation was assessed with the use of immunological surface markers of acti vation (ligand-induced binding site 1 [LLBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly in creased in patients with diffuse disease when compared with focal transplan t disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predicto r for the presence and progression of diffuse transplant vasculopathy (P=0. 04). Patients with enhanced LIBS-1 levels (>75% gut-tile) had a 3.3-fold in creased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence of di ffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1 .9 and 12.5, P<0.01) for the progression of transplant vasculopathy. Conclusions-Enhanced platelet activation is strongly associated with the de velopment and progression of transplant vasculopathy. Understanding the und erlying pathophysiological mechanisms might contribute to the development o f treatment strategies to prevent transplant vasculopathy.