Thrombotic thrombocytopenic purpura that is refractory to therapeutic plasma exchange in two patients with occult infection

BACKGROUND: The etiology of thrombotic thrombocytopenic purpura (TTP) remains undetermined. TTP has been associated with a number of secondary causes including infections, drugs, menses, pregnancy, autoimmune diseases, and bone marrow transplantation. Regardless of the inciting factors, it is widely accepted that endothelial injury and platelet aggregation are integral components. The morbidity and mortality have been significantly reduced with the use of plasmapheresis. However, refractory forms of TTP remain a clinical management challenge. Refractory TTP has not previously been associated with occult bacterial infection. CASE REPORT: Two patients had classic TTP that was refractory to daily plasma exchange with fresh-frozen plasma. Multiple attempts over a period of months to wean these patients off plasma exchange resulted in exacerbations of disease activity, as indicated by increased schistocytosis, decreased hematocrit, increased serum lactate dehydrogenase, and decreased platelet counts. Both patients were empirically treated for infections during hospitalization, although microbial cultures failed to isolate an organism. Discontinuation of antimicrobial therapy on multiple occasions in one patient was associated with recurrence of disease. In the other patient, dental extraction with drainage of an occult periodontal abscess resulted in sustained remission of disease. CONCLUSION: Occult bacterial infection may play a role in triggering and sustaining TTP that is refractory to conventional treatment. A careful search for such an infection and appropriate antimicrobial therapy should be considered in the management of these patients.