Can Thrombotic Thrombocytopenic Purpura (TTP) be triggered by infection?

Infections as Triggers for Thrombotic Thrombocytopenic Purpura (TTP)

Yes, infections can trigger Thrombotic Thrombocytopenic Purpura (TTP), with various viral and bacterial pathogens documented as potential precipitating factors for this life-threatening condition. 1, 2, 3

Mechanism and Evidence

Infections can trigger TTP through several mechanisms:

1. Immune System Activation: Infections may lead to immune stimulation that triggers autoantibody formation against ADAMTS13 (the enzyme that cleaves von Willebrand factor), resulting in acquired TTP 3

2. Endothelial Damage: Some infections directly damage vascular endothelium, which can precipitate the microvascular thrombosis characteristic of TTP 1

3. Relapse Trigger: In patients recovering from TTP, new infections can trigger early relapse, necessitating renewed treatment 2

Documented Infectious Triggers

Multiple infectious agents have been associated with TTP:

• Viral infections:

  • COVID-19 4
  • Influenza A virus (including H1N1 subtype) 5
  • Cytomegalovirus (CMV) 1, 3
  • Epstein-Barr virus 3
  • Human herpes virus 6 and 8 1

• Bacterial infections:

  • Helicobacter pylori 6
  • Urinary tract infections 2
  • Various other bacterial pathogens 3

• Other infections:

  • Tuberculosis 1
  • Toxoplasmosis 1
  • Pneumocystis pneumonia 1

Clinical Implications

The relationship between infections and TTP has important clinical implications:

1. Diagnostic challenges: Systemic infections can mimic TTP's presenting features, making diagnosis difficult. In one registry, 7% of patients initially diagnosed with TTP were subsequently found to have systemic infections causing similar clinical manifestations 3

2. Treatment considerations:

   • When infection is suspected as a trigger for TTP, appropriate antibiotic therapy should be instituted promptly 2
   • In some cases, treating the underlying infection may lead to resolution of TTP 6
   • Initial plasma exchange is still appropriate in critically ill patients with diagnostic features of TTP, even if infection is suspected 3

3. Monitoring for infections: Vigilance for new infections is essential in TTP patients undergoing treatment, as these can trigger relapses 2

Diagnostic Approach

When evaluating patients with suspected TTP:

• Consider infection as both a potential trigger and a differential diagnosis
• Perform appropriate infectious workup including blood cultures, urinalysis, chest imaging, and specific tests based on clinical presentation
• Remember that the presence of infection does not rule out TTP - they can coexist, with infection triggering TTP 3
• Be aware that some patients with infection-associated TTP may have severe ADAMTS13 deficiency with demonstrable inhibitors 3

Treatment Algorithm

1. For patients presenting with clinical features of TTP:

   • Begin plasma exchange promptly if TTP is suspected clinically
   • Simultaneously evaluate for potential infectious triggers
   • Obtain ADAMTS13 activity and inhibitor levels before plasma exchange if possible

2. If infection is identified:

   • Initiate appropriate antimicrobial therapy immediately
   • Continue plasma exchange if TTP diagnosis remains likely
   • Monitor response to both antimicrobial therapy and plasma exchange

3. For refractory cases:

   • Consider undiagnosed or inadequately treated infection as a potential cause
   • Targeted testing for specific pathogens like H. pylori may be warranted 6
   • Consider additional immunosuppressive therapy (e.g., rituximab) if TTP persists despite infection control 2

Pitfalls and Caveats

• Misdiagnosis risk: The clinical features of severe systemic infections can closely mimic TTP, potentially leading to unnecessary plasma exchange 3
• Delayed diagnosis: Focusing exclusively on TTP may delay identification and treatment of underlying infections
• Treatment complications: Immunosuppressive treatments for TTP may worsen outcomes in patients with active infections
• Incomplete evaluation: Failure to perform comprehensive infectious workup in TTP patients may miss treatable triggers

Remember that the relationship between infections and TTP is bidirectional - infections can both trigger TTP and mimic its presentation. A thorough diagnostic evaluation and appropriate management of both conditions are essential for optimal patient outcomes.