Thrombotic thrombocytopenic purpura

Background

Pathophysiology

• Insufficient ADAMTS-13 activity allows vWF multimers to accumulate in microcirculation which leads to platelet aggregation/thrombocytopenia and hemolysis of RBCs. Platelet clots are transient, but the symptoms especially neuro, can be in flux.

• Similar clinical symptoms but different pathophysiology than HUS
  • HUS More common in pediatrics
• Microangiopathic Hemolytic Anemia (MAHA) + low Platelets is TTP until proven otherwise
• Can occur as a result of Plavix (clopidogrel) use, especially within the first 2 weeks

Risk Factors

Congenitally deficient ADAMTS-13 activity AND

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

Clinical Features

Pentad (rarely all present)

1. Microangiopathic Hemolytic Anemia (MAHA)
2. Thrombocytopenia
3. Fever
4. Renal pathology
5. CNS abnormalities (seizure, AMS, CVA, coma)
   • Neuro symptoms are often transient, may not be present in ED

TTP pentad mnemonic = FAT RN

• Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms

• All features DO NOT need to be present at the same time
• Consider diagnosis without the full pentad

Differential Diagnosis

• Other MAHAs (eg, HUS, DIC, malignant hypertension)
• ITP
• Sepsis
• SLE
• HELLP syndrome
• Anemia, platelet count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP

Work-Up

• CBC with peripheral smear (anemia, schistocytes, thrombocytopenia are suggestive findings)
• 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

All treatments should be performed with a hematology consultation

1. Plasma exchange (plasmapheresis)
   • Replaces defective or insufficient ADAMTS-13 and clears vWF multimers
2. Transfusion of RBCs (only severe bleeding)
   • Generally only indicated if plasma exchange cannot be performed immediately
3. FFP Transfusion
   • Contains ADAMTS-13
   • Should only be initiated if delay in plasmapheresis
4. Platelet Transfusion is AVOIDED
   • Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
   • Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
5. Splenectomy - 2nd line therapy after stabilization

Disposition

• Admit for plasma exchange

See Also

• Microangiopathic Hemolytic Anemia (MAHA)
• HUS
• DIC
• HELLP, SLE, Antiphospholipid Syndrome (APS)
• ITP

Source

• Hirsh J et al. [Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(Suppl):110S-112S http://journal.publications.chestnet.org/pdfaccess.ashx?ResourceID=2124970&PDFSource=13]