Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection

A review of the histopathologic features of serial biopsies and excised gra fts of 117 experimental and clinical cardiac allografts and xenografts reve aled a common sequence in the development of histopathologic changes in gra fts showing antibody-mediated (hyperacute and acute vascular) rejection. Ba sed on these observations, we propose the new concept that thrombosis of ca rdiac veins and venules is the initial key event in antibody-mediated rejec tion. This is followed by the development of congestion in the subtended ve nules and capillaries accompanied by interfascicular and, later, intermyocy te edema. Subsequently, focal or diffuse interstitial hemorrhage affecting the subendocardium, extending sometimes to involve the inner half of the ve ntricular myocardium, is observed. Antibody-mediated rejection therefore ap pears to be analogous to incomplete venous infarction of the heart. The obs erved histopathology (in which venular thrombosis plays a key role) favors a thrombogenic basis for the classical features of antibody-mediated reject ion, namely edema, vascular thrombi and interstitial hemorrhage. A key role for venular thrombosis would explain the non-uniform distribution of the c hanges and may suggest new ways of preventing antibody-mediated xenograft r ejection.