What are the latest guidelines for treating Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)?

Latest Guidelines for Treating TTP and HUS

For Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS), immediate therapeutic plasma exchange (TPE) is the cornerstone of treatment for TTP, while eculizumab is indicated for atypical HUS (aHUS) but not for Shiga toxin-related HUS. 1, 2

Diagnosis and Initial Evaluation

• Test for ADAMTS13 activity level and inhibitor titer to distinguish TTP from other thrombotic microangiopathies 1
• Examine peripheral blood smear for schistocytes, which is critical for diagnosis 1
• Check LDH, haptoglobin, reticulocyte count, bilirubin, and urinalysis to assess hemolysis 1
• Test coagulation parameters including prothrombin time, activated partial thromboplastin time, and fibrinogen 1
• Screen for potential secondary causes including HIV, HCV, and H. pylori 1

Treatment of TTP

First-line Treatment

• Initiate therapeutic plasma exchange (TPE) immediately upon diagnosis 1

  • Exchange 1-1.5 times plasma volume daily until platelet count normalizes (>150 × 10^9/L) and LDH normalizes 3
  • Fresh frozen plasma (FFP) is the standard replacement fluid; cryosupernatant plasma has not shown superior efficacy in randomized trials 4

• Administer high-dose corticosteroids concurrently with TPE 1, 3

  • Methylprednisolone 1g IV daily for 3 days, with first dose typically given immediately after first TPE 1
  • Continue with prednisone 1-2 mg/kg/day 1

Refractory or Relapsed TTP

• Consider rituximab for patients who fail to respond to initial TPE and corticosteroids 1
• For life-threatening TTP (Grade 4) 1:
  • Continue daily TPE
  • Consider additional immunosuppressive agents such as rituximab, IVIG, cyclosporine, infliximab, or mycophenolate mofetil 1

Treatment of Hemolytic Uremic Syndrome (HUS)

Atypical HUS (aHUS)

• Eculizumab (Soliris) is indicated for aHUS to inhibit complement-mediated thrombotic microangiopathy 2
  • Adult dosing: 900 mg weekly for first 4 weeks, followed by 1200 mg for fifth dose 1 week later, then 1200 mg every 2 weeks 2
  • Pediatric dosing: Weight-based according to FDA label 2
  • Important safety note: Meningococcal vaccination required at least 2 weeks prior to initiation 2

Shiga toxin-related HUS (STEC-HUS)

• Eculizumab is NOT indicated for Shiga toxin E. coli related HUS 2
• Supportive care is the mainstay of treatment 2

Special Considerations

• For pregnant patients with TTP: TPE remains the first-line treatment; corticosteroids can be used concurrently 1
• For secondary TTP:
  • HCV-associated: Consider antiviral therapy if no contraindications; use IVIG for initial treatment of thrombocytopenia 1
  • HIV-associated: Treat underlying HIV infection with antivirals unless urgent bleeding complications present 1

Prognostic Factors

• Advanced age and severe renal impairment (creatinine >2 mg/dL) are associated with poor treatment outcomes 5
• Presence of fever may indicate worse prognosis and need for prolonged TPE 6
• Early initiation of TPE is associated with improved survival rates 3

Follow-up and Monitoring

• Monitor platelet count and LDH daily during active treatment 3
• After remission, gradually taper TPE frequency rather than abrupt discontinuation 6, 3
• Long-term follow-up is essential as relapses can occur, particularly within the first 2 years after initial episode 5