Thrombotic thrombocytopenic purpura

Background

• Pathophysiology
  • Insufficient ADAMTS-13 activity allows vWF multimers to accumulate in microcirculation
    • Leads to platelet aggregation/thrombocytopenia and hemolysis of RBCs
• Similar to but different from HUS (which is more common in peds)
• Microangiopathic hemolytic anemia + low plts is TTP until proven otherwise

Risk Factors

• Congenitally deficient ADAMTS-13 activity and:

1. Pregnancy
2. Infection
3. Inflammation
4. Medication use (quinolones, ticlopidine, clopidogrel)

Clinical Features

• Pentad

1. Microangiopathic hemolytic anemia
2. Thrombocytopenia
3. Fever
4. Renal pathology
5. CNS abnormalities (seizure, AMS, CVA, coma)

• TTP pentad mnemonic = FAT RN
  • Fever, Anemia, Thrombocytopenia, Renal, Neuro sx

DDX

• Other microangiopathic hemolytic anemias (HUS, DIC, malignant HTN)
• ITP
• Sepsis
• SLE
• HELLP syndrome
  • Difficult to distinguish
  • Anemia, plt count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP

Work-Up

• CBC with peripheral smear (anemia, schistocytes, thrombocytopenia)
• LDH (elevated)
• Haptoglobin (decreased)
• Reticulocyte count (appropriate)
• UA (hemoglobinuria)
• Creatinine (possibly elevated)
• LFTs (increased bilirubin)
• PT/PTT/INR (normal; differentiates from DIC)
• Urine pregnancy (significant association between pregnancy and TTP)

Treatment

• Plasma exchange (plasmapheresis)
  • Replaces defective or insufficient ADAMTS-13 and clears vWF multimers
• Transfusion
  • Indicated if plasma exchange cannot be performed immediately
  • FFP
  • Platelet (only for life-threatening bleeding or intracranial hemorrhage)
    • Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
• Splenectomy - 2nd line therapy

Disposition

• Admit for plasma exchange

Source

• Tintinalli
• Harwood Nuss