Table 1.

Genesis and characteristics of VMTD in TTP and TTP-like syndrome

	Hereditary TTP (GA-VMTD) Acquired TTP (AA-VMTD)	TTP-like syndrome (EA-VMTD)
Primary causes/events	Hereditary ADAMTS13 gene mutation Acquired ADAMTS13 antibody formation ↓	Pathogen (e.g., viruses; bacteria; fungi; rickettsia; parasites) Polytrauma (e.g., chest/lung; bone; skull/brain injury) Pregnancy (e.g., preeclampsia; abruptio placenta; amniotic fluid embolism) Cancer (e.g., disseminated stomach/breast/lung cancer) Transplant (e.g., liver; kidney; bone marrow) Drug and toxin (e.g., cyclosporine; mitomycin C; Shiga toxin) ↓
Secondary event	Excessive circulating mULVWF ↓	Complement activation (C5b-9) and endothelial injury → endotheliopathy ↓
Tertiary event	Microthrombogenesis → platelet-ULVWF complexes ↓ Microthrombi lodged in arteriolar and capillary lumens ↓	Cytokine release → inflammation → SIRS Platelet activation and endothelial exocytosis of eULVWF ↓ Microthrombogenesis → platelet-ULVWF complex strings ↓
Final event	Microvascular microthrombosis ↓ DIT/VMTD ↓ TTP	Vascular microthrombosis ↓ DIT/VMTD ↓ TTP-like syndrome
Hematologic features
Platelet	Consumptive thrombocytopenia	Consumptive thrombocytopenia
Red blood cell	MAHA	MAHA/aMAHA
Clinical syndromes
Inflammation	Uncommon	Very common
Cytokine storm	Absent	Often present in sepsis and MODS
SIRS	Absent	Often present in sepsis and MODS
Encephalopathy	Very common	Common, especially in HUS
ARDS	Probably absent	Common
AFHF	Probably absent	Common, sometimes with hepatic coagulopathy
ARF/HUS	Very common	Common
“DIC” (see text)	Doesn’t occur	Identical to TTP-like syndrome
Laboratory features
ADAMTS13 activity	Markedly decreased (< 5% of normal)	Mild to moderately decreased (20–70% of normal)
ADAMTS13 antibody	Positive in acquired TTP	Negative
Haptoglobin	Markedly decreased	Markedly decreased
Schistocytes	++ to ++++	None to +++
Therapeutic response to
TPE	Very good response	Excellent and fast response if treated in early stage
Platelet transfusion	Contraindicated	Contraindicated
rADAMTS13	Unknown; expected to be effective in GA-VMTD	Unknown; expected to be very effective

AFHF acute fulminant hepatic failure, ARF/HUS acute renal failure/hemolytic uremic syndrome, ARDS acute respiratory distress syndrome, “DIC” disseminated intravascular coagulation of McKay, ECs, endothelial cells, eULVWF/mULVWF endothelial unusually large von Willebrand factor/megakaryocytic ULVWF, LDH lactate dehydrogenase, MAHA/aMAHA microangiopathic hemolytic anemia/atypical MAHA, rADAMTS13 recombinant ADAMTS13, SIRS, systemic inflammatory response syndrome, TMA thrombotic microangiopathy TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura, VMTD vascular microthrombotic disease