Interventions for Haemolytic Uraemic Syndrome (Hus) and Thrombotic Thrombocytopenic Purpura (TTP)

A Cochrane review [Abstract] 1 included 6 studies on thrombotic thrombocytopenic purpura (TTP) with a total of 331 subjects and 7 studies on haemolytic uraemic syndrome (HUS) with a total of 476 children. In the TTP studies, plasma exchange (PE) with fresh frozen plasma (FFP) was the control. Any of the interventions tested in the RCTs (PE with cryosupernatant plasma (CSP) or cryoprecipitate poor plasma (CPP); plasma infusion (PI) and antiplatelet therapy (APT); or PE with FFP and APT) provided no significant additional benefit over PE with FFP with regard to any of the outcomes of interest (failure of remission, all-cause mortality and relapse rate). 2 studies comparing plasma infusion (PI) to PE with FFP showed a significant increase in failure of remission at two weeks (RR 1.48, 95% 1.12 to 1.96) and all-cause mortality (RR 1.91, 95% 1.09 to 3.33) in the PI group. Some patients with TTP require prolonged PE to prevent a fatal outcome and to achieve a sustained remission. In these patients adjunct treatments including immunosuppressive agents such as corticosteroids, vincristine, cyclophosphamide, azathioprine, cyclosporin A, high dose intravenous immunoglobulin, staphylococcal protein A, immunoadsorption or splenectomy have been used with variable results. However, no RCTs testing the effectiveness of any of these interventions were found.

The HUS studies included children. None of the assessed interventions used (FFP transfusion, heparin with or without urokinase or dipyridamole, shiga toxin binding protein and steroids) were superior to supportive therapy (including blood transfusion, control of fluid and electrolyte imbalance, dialysis when indicated and control of hypertension) alone, for all-cause mortality, neurological/extrarenal events, renal biopsy changes, proteinuria or hypertension at the last follow-up visit. Bleeding was significantly higher in those receiving anticoagulation therapy compared to supportive therapy alone (RR 25.89, 95% CI 3.67 to 182.83). There were no RCTs evaluating the effectiveness of any interventions including PI or PE on patients with atypical HUS who have a more chronic and relapsing course and present with features similar to TTP.

Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).

References

• Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev 2009 Jan 21;(1):CD003595. [PubMed]