TTP – Classifications

By William Aird

Classifications

Thrombotic microangiopathy (TMA):
- Primary:
  - TTP (see below)
  - Complement-mediated HUS (CM-HUS) – also known as atypical HUS (aHUS)
- Secondary:
  - Connective tissue disease:
    - Scleroderma renal crisis (SRC)
    - Systemic lupus erythematosus
    - Antiphospholipid antibody syndrome
    - Vasculitis (typically presents with a renal-limited phenotype)
  - Malignant hypertension
  - Transplant-associated TMA:
    - Hematopoietic stem cell transplantation
    - Solid organ transplantation
  - Infection:
    - Shiga toxin-producing Escherichia coli (STEC)-HUS
    - Streptococcus pneumoniae-HUS (SP-HUS)
    - HIV
    - HCV
    - CMV
    - EBV
    - Herpes simplex virus
    - Adenovirus
  - Disseminated intravascular coagulation (DIC)¹
  - Pregnancy-associated TMAs:
    - HELLP syndrome
    - Pre-eclampsia
  - Drug-induced TMA:
    - Quinine
    - Calcineurin inhibitors (cyclosporin and tacrolimus)
    - Proteasome inhibitors
    - Gemcitabine
    - Mitomycin C
  - Pancreatitis-associated TMA
  - Cancer-associated TMA
  - Postsurgery TMA
  - Metabolism-mediated TMA (cobalamin C-defect TMA)
  - Coagulopathy-related TMA:
    - DGKE mutation
    - PLG mutation
    - THBD mutation
Microangiopathic hemolytic anemia (MAHA):
- In presence of platelet or fibrin clots:
  - TTP
  - HUS
  - Disseminated malignancy
  - Malignant hypertension
  - Severe preeclampsia
  - Cavernous hemangioma
  - Disseminated intravascular coagulation (DIC)
- In absence of platelet or fibrin clots:
  - Prosthetic heart valves
  - Ventricular assisted devices
  - Extracorporeal membrane oxygenation
Hemolytic uremic syndrome (TMA manifested primarily by kidney injury secondary to fibrin and platelet thrombi in capillaries and arterioles):²
- Infection-associated:
  - Shiga toxin-producing Escherichia coli (STEC)-HUS
  - Streptococcus pneumoniae-HUS (SP-HUS)
  - H1N1 influenza A
- Atypical hemolytic uremic syndrome:
  - Primary:
    - Complement-mediated HUS
    - Metabolism-associated HUS:
      - Cobalamin C (cblC) disease
      - Diacylglycerol kinase ε DGKE and WT1-associated HUS
  - Secondary (implies another underlying cause for disease):
    - Infections:
      - HIV
      - Cytomegalovirus
      - Epstein-Barr virus
      - Varicella zoster virus
      - Parvovirus B19
      - Malaria
      - Dengue fever
    - Malignant hypertension
    - Autoimmune diseases
    - Cancers
    - Medications
    - Transplantation
Thrombotic thrombocytopenic purpura (TTP):
- Congenital TTP (cTTP) (Upshaw–Schulman syndrome)
- Immune mediated TTP (iTTP) (also called autoimmune TTP or acquired TTP):³
  - Primary iTTP:
    - No obvious underlying precipitating cause/disease.
    - ADAMTS-13 activity of< 10% with the presence of ADAMTS-13 autoantibodies.
    - Accounts for the majority of cases of TTP.
  - Secondary iTTP:⁴
    - Precipitating cause (underlying disorder or trigger) can be identified, including:
      - Connective tissue disease:
        
        SLE
        
        Sjogren’s syndrome
        
        Rheumatoid arthritis
      - HIV infection
      - Cytomegalovirus infection
      - Pregnancy
      - Drugs:
        
        Ticlodipine
        
        Quinine
        
        Simvastatin
        
        Trimethoprim
        
        Pegylated interferon
    - ADAMTS-13 activity of <10% with the presence of ADAMTS-13 autoantibodies.

Want to explore this further?

Check out the related sections in our TTP module:

TTP Classifications – Quiz
TTP/TMA Classification Graphic
TTP Definitions

Stay Updated

If you are interested in getting the latest articles from The Blood Project, enter your name and email