What is the management approach for a patient with Enteropathogenic Escherichia coli (EPEC) infection and Thrombotic Thrombocytopenic Purpura (TTP)?

Management of EPEC Infection with Thrombotic Thrombocytopenic Purpura (TTP)

The management of a patient with Enteropathogenic Escherichia coli (EPEC) infection and Thrombotic Thrombocytopenic Purpura (TTP) requires immediate therapeutic plasma exchange (TPE), corticosteroids, and rituximab, along with supportive care and appropriate treatment of the underlying EPEC infection.

Diagnosis and Initial Assessment

• TTP is characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet-rich thrombi 1
• Diagnostic workup should include:
  • Complete blood count with peripheral smear to check for schistocytes 2
  • ADAMTS13 activity level and inhibitor titer (severely reduced ADAMTS13 activity <10% confirms TTP) 2, 3
  • LDH, haptoglobin, reticulocyte count, bilirubin, and urinalysis 2
  • Prothrombin time, activated partial thromboplastin time, and fibrinogen 2
  • Blood group and antibody screen, and direct antiglobulin test 2
  • Stool culture to confirm EPEC infection 2

Management of TTP

First-line Treatment

• Immediate hematology consultation is essential as delay in identification is associated with increased mortality and morbidity 2
• Initiate therapeutic plasma exchange (TPE) immediately:
  • Daily TPE using fresh frozen plasma to supply deficient ADAMTS13 and remove autoantibodies 4, 1
  • Continue TPE until platelet count normalizes and clinical improvement is observed 2
• Administer high-dose corticosteroids:
  • Methylprednisolone 1g IV daily for 3 days, with first dose typically administered immediately after first TPE 2
  • Then transition to prednisone 1-2 mg/kg/day 2
• Add rituximab (375 mg/m² weekly for 4 weeks) to suppress autoantibody production 4, 3
• Consider caplacizumab if ADAMTS13 activity level is normal with an inhibitor or elevated anti-ADAMTS13 IgG 2, 3
  • Caplacizumab blocks platelet binding to vWF, reduces time to platelet count normalization, and decreases early recurrence risk 3

Management of Allergic Reactions to Plasma

• If patient develops allergic/anaphylactic reactions to donor plasma during TPE, consider:
  • Using Octaplas (solvent and detergent-treated, type-specific, pooled donor plasma) instead of standard plasma 5
  • Alternatively, use albumin with slowly increasing amounts of standard plasma 5

Management of EPEC Infection

• Avoid antibiotics for EPEC infection if possible, as antibiotic therapy in patients with STEC infections might be associated with more severe disease 2
• Provide aggressive parenteral volume expansion to decrease renal damage and improve patient outcome 2
• Supportive care with careful fluid and electrolyte management 2
• Monitor for development of hemolytic uremic syndrome (HUS), which can occur with EPEC infection 2

Monitoring and Follow-up

• Monitor hemoglobin levels weekly until steroid tapering process is complete 2
• Regular monitoring of platelet count, LDH, and clinical symptoms 2, 3
• After obtaining clinical remission (defined as at least 30 days of sustained normalization of platelet count, decreased LDH, and absence of new or progressive ischemic organ injury), continue monitoring ADAMTS13 activity 3
• Consider administering rituximab when ADAMTS13 activity is less than 20% to reduce risk of relapse 3

Special Considerations

• Infections (including bacterial infections like EPEC) may trigger exacerbations or relapses of TTP 6
• Prompt treatment of the underlying infection is crucial to prevent TTP exacerbations 6
• Long-term follow-up is essential to identify occurrence of other autoimmune diseases, control relapses, and evaluate psychophysical sequelae 1

Pitfalls and Caveats

• Do not delay TPE while waiting for ADAMTS13 results; treatment should be initiated based on clinical suspicion 2, 3
• Avoid platelet transfusions unless there is life-threatening bleeding, as they can worsen microvascular thrombosis 2
• Be vigilant for infections that may develop during immunosuppressive therapy 6
• Monitor for bleeding complications, especially if caplacizumab is used 3
• Recognize that TTP has a relapsing tendency, requiring long-term monitoring 1