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Table 1 Genesis and characteristics of VMTD in TTP and TTP-like syndrome

From: TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease

  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
  1. 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