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 |