Table 2.

Pathogenetic difference of VMTD between TTP and sepsis-associated TTP-like syndrome

	TTP (GA-VMTD and AA-VMTD)	TTP-like syndrome in sepsis (EA-VMTD)
Primary event	Hereditary TTP (GA-VMTD)	Sepsis due to pathogens
	(due to mutation of ADAMTSD13 gene)	(e.g., bacteria; viruses; fungi; rickettsia; parasites)
	Acquired TTP (AA-VMTD)	↓
	(due to anti-ADAMTS13 antibody)	Complement activation → MAC (C5b-9) formation (?)
	↓	↓
Secondary event	Excess of circulating ULVWF & platelets	C5b-9-induced endotheliopathy
	↓	↓
	Microthrombogenesis, leading to ULVWF-platelet complex formation in microcirculation	ULVWF released from ECs & anchored to endothelial membrane to recruit platelets → microthrombogenesis
	↓	↓
Tertiary event	Microthrombi in microvasculatures	Microthrombi strings in smaller and larger vasculatures
	↓	↓
Final event	Microvascular thrombosis	Vascular microthrombosis
	↓	↓
	GA-VMTD; AA-VMTD	EA-VMTD
	↓	↓
	TTP	TTP-like syndrome

Abbreviations: ECs endothelial cells, MAC membrane attack complex, TTP thrombotic thrombocytopenic purpura, VMTD vascular microhrombotic disease, AA-VMTD antibody-associated VMTD, EA-VMTD endotheliopathy-associated VMTD, ULVWF unusually large von Willebrand factor multimers