Table 1.

Summary of current literature supporting a damaging role of hemolysis in different organs.

Organ	Impact of heme damage	References	Disease/model
Kidney	Proximal tubule dysfunction and impaired vitamin D metabolism	(247, 248)	Cell culture/mice
	Proteinuria, acute and chronic injury, and iron deposition	(244, 245, 249–253)	Human
	Acute renal failure, oxidative stress, inflammation, and toxicity	(254–257)	Human/mice
	Acute renal vasoconstriction via TLR4 signaling	(258, 259)	Cell culture/Mice
	Apoptosis in proximal tubular epithelial cells via caspase-dependent/-independent pathways	(260, 261)	Cell culture
	Endothelial apoptosis and vaso occlusion	(262)	Human/cell culture/mice
Lung	Acute chest syndrome via TLR4, NRF2 and p-selectin signaling	(133, 196, 263)	Cell culture/mice
	Oxidative injury and progression of pulmonary hypertension (PH)	(262)	Cell culture/mice
	Angioproliferative PH via accelerated purine metabolism	(264)	Rats
	Acute lung injury via increased alveolar capillary barrier dysfunction	(265, 266)	Human/cell culture/mice
	Oxidation and mitochondrial dysfunction in epithelial lung cells	(36)	Cell culture
Liver	Increased vascular ICAM-1 expression on blood vessels and vaso occlusion	(267)	Cell culture/mice
	Advanced fibrosis and iron overload	(268)
	Oxidative stress, neutrophil infiltration, and extravasation through NF-κB activation	(269)
Heart	Impaired nitric oxide bioavailability and pulmonary hypertension	(270, 271)	Mice
	Smooth muscle proliferation via NADPH oxidase activity, atherosclerosis, and hypertension	(101, 272)	Cell culture
	Increased risk of cardiovascular disease	(273, 274)	Human
	Endothelial activation and altered cardiac function	(275, 276)	Mice
	Mitochondria dysfunction	(277)	Human/cell line
	Ischemic injury	(278)	Human/cell culture/mice
	Contractile dysfunction due to altered contractile proteins	(279)	Human primary cardiomyocytes