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
  

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:

• 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