Table 1.

Histology of cardiac xenograft rejection

Donor type	HAR	DXRa	TM/CCa,b
Wild type	• Acute rapid graft failure within minutes or hours after reperfusion	• Occurs days to weeks after transplantation	• Occurs days to weeks after transplantation
	• Extensive vascular antibody and complement deposition	• Vascular antibody and variable complement deposition	• Vascular antibody and complement deposition is variable
	• Prominent vascular injury and hemorrhage	• Intravascular injury and hemorrhage	• Minimal vascular hemorrhage
		• Prominent diffuse platelet-rich fibrin thrombosis	• Myocyte vacuolization.
	• Some platelet and fibrin thrombi may be present The expected outcome for transplantation of wild-type organs into untreated recipients	• Coagulative necrosis Requires pre-transplant therapies to limit immediate antibody- and complement-mediated graft injury	• Fibrin- and platelet-rich microvascular thrombosis.
			• Coagulative necrosis Requires rigorous pre- and post-transplant prevention of an anti-Gal antibody response
GTKO	Histology is comparable to wild-type donor organs, but the frequency of GTKO HAR is dramatically lower.	• Occurs days to months after transplantation.
		• Vascular antibody and complement deposition is variable
		• Minimal intravascular hemorrhage
		• Myocyte vacuolization
		• Fibrin- and platelet-rich microvascular thrombi
		• Coagulative necrosisTypical histopathologic picture in GTKO organs in immune-suppressed recipients with low-to-moderate levels of anti-non-Gal antibody.

^aDXR and TM/CC typically show low levels of polymorphonuclear neutrophil and macrophage graft vascular adhesion and infiltration, with little apparent lymphocytic infiltrate. In TM/CC, increased levels of macrophage infiltration may accompany systemic innate cell activation.

^bTM and CC may occur individually or in combination. TM is localized to the graft, and CC is an intravascular process with significant recipient thrombocytopenia and systemic fibrin consumption.