Interventions for Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura: A Systematic Review of Randomized Controlled Trials
Received 25 February 2008; accepted 30 July 2008. published online 28 October 2008.
Background
Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. The objective of this systematic review is to evaluate the benefits and harms of available interventions for HUS and TTP.
Selection Criteria for Studies
MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), the Cochrane Central Register, conference proceedings, and reference lists were searched to find randomized controlled trials (RCTs) of any intervention for HUS or TTP in patients of all ages selected for inclusion for this systematic review.
Interventions
Trials that compared an intervention with placebo, an intervention with supportive therapy, or one or more different interventions for HUS or TTP.
Outcomes
For TTP trials, failure of remission at 2 weeks or less and at 1 month or longer, all-cause mortality rate, and relapse rate. For HUS trials, all-cause mortality, chronic reduced kidney function, and persistent proteinuria or hypertension at last follow-up.
Results
For TTP in adults, we found 6 RCTs of 331 patients. Two trials compared plasma infusion with plasma exchange using fresh frozen plasma and showed failure of remission at 2 weeks (2 trials, 140 patients; relative risk, 2.87; 95% confidence interval, 1.41 to 5.84), and all-cause mortality (relative risk, 1.91; 95% confidence interval, 1.09 to 3.33) occurred more frequently in the plasma infusion group. Three trials compared plasma exchange using cryosupernatant plasma with plasma exchange using fresh frozen plasma, and a meta-analysis of these trials showed no difference. Seven RCTs in 476 young children with postdiarrheal HUS have been conducted. None of the evaluated interventions (fresh frozen plasma transfusion, heparin with or without urokinase or dipyridamole, Shiga toxin–binding protein, and steroid) were superior to supportive therapy alone for any outcomes.
Limitations
Limitations of this review include the small number and suboptimal quality of reporting of included trials, possibility of publication bias, small number of participants with atypical HUS, and failure to report results for patients with atypical and typical HUS separately.
Conclusions
No additional therapy has been shown to increase efficacy over plasma exchange for TTP. No intervention has been shown to be superior to supportive therapy in patients with postdiarrheal HUS.
1Renal Section/Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
2Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia
3Centre for Evidence Based Paediatric Gastroenterology and Nutrition, Cochrane Renal Group, The Children's Hospital at Westmead, Sydney, Australia
4Australian Paediatric Surveillance Unit, Cochrane Renal Group, The Children's Hospital at Westmead, Sydney, Australia
5Centre for Kidney Research, Cochrane Renal Group, The Children's Hospital at Westmead, Sydney, Australia
6School of Public Health, University of Sydney, Sydney, Australia
Address correspondence to Mini Michael, MBBS, FRACP, MM(Clin Epi), Renal Section/Department of Pediatrics, Baylor College of Medicine, 6621 Fannin St, MC 3-2482, Houston, TX 77030
ABSTRACT