Thrombotic Microangiopathies

Case Presentation:

In our Morning Report at WCH, we discussed a case of a patient presenting acute anemia and thrombocyotopenia (recent CBC 2 weeks prior = normal). Subsequent investigations were compatible with microangiopathic hemolytic anemia, also referred to as thrombotic microangiopathy (TMA).

Learning Points:

  1. The Acute Drop in Hemoglobin
  2. Hemolysis Work-Up
  3. Definition and types of thrombotic microangiopathy
  4. TTP vs DIC
  5. Causes of DIC

Acute Drop in Hemoglobin:

  • the classic approach to anemia involves stratification into micro/normo/macrocytic
  • in the acute/subacute setting (i.e. the hemoglobin level has changed dramatically in a short period of time), I find the following approach a bit more useful
    acute-drop-in-hb

Hemolysis Work-Up:

  • CBC
  • Reticulocyte Count
  • Blood Film
  • Indirect (unconjugated) bilirubin
  • LDH
  • Haptoglobin
  • Direct antiglobulin test
  • INR, aPTT
  • D-dimer, fibrinogen

Definition and types of TMA:

  • TMA=Microangiopathic hemolytic anemia (MAHA) + thrombocytopenia
  • Examples include:
    • Thrombotic thrombocytopenic purpura
    • Atypical HUS
    • Disseminated intravascular coagulation
    • HTN-related (Scleroderma Renal Crisis, Malignant HTN)
    • Catastrophic antiphospholipid antibody syndrome
    • Pregnancy-related (HELLP)
    • Stem Cell or Solid-organ Transplant-related

TTP vs DIC:

  • Both are associated with MAHA, thrombocytopenia, elevated LDH, low haptoglobin, elevated bilirubin, and schistocytes on blood film
  • In infection or sepsis-related DIC, AKI may also be present much like in TTP
  • Distinguishing feature: coagulation parameters are abnormal in DIC but characteristically unaffected in TTP
    • DIC: Prolonged INR and aPTT with elevated D-dimer and low fibrinogen
    • TTP: Normal INR and aPTT with normal-slightly elevated D dimer and elevated fibrinogen

Causes of DIC:

dic-causes

  • any major infection or bacteremia can trigger DIC
  • Meningococcemia specifically can be associated with DIC that leads to purpura fulminans and bilateral adrenal hemorrhage (Waterhouse-Friderichsen Syndrome)
  • Acute promyelocytic leukemia (APML) classically is associated with a DIC picture
  • Certain solid-organ malignancies like pancreatic cancer may be associated with DIC
  • Other causes include heat stroke, toxic overdoses, snake bites, and hereditary protein C deficiency

Further Reading:

  1. George, JN;  Nester, CM. Syndromes of Thrombotic Microangiopathy. N Engl J Med. 2014 Aug 14;371(7):654-66. doi: 10.1056/NEJMra1312353

 

 

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