TRANSFUSION PRACTICE Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials Lucy Yang, Simon Stanworth, Sally Hopewell, Carolyn Doree, and Mike Murphy BACKGROUND: The clinical use of frozen plasma (FP) continues to increase, both in prophylactic and in thera- peutic settings. In 2004, a systematic review of all pub- lished randomized controlled trials (RCTs) revealed a lack of evidence that supported the efficacy of FP use. This is an update that includes all new RCTs published since the original review. STUDY DESIGN AND METHODS: Trials involving transfusion of FP up to July 2011 were identified from searches of MEDLINE, EMBASE, CINAHL, The Cochrane Library, and the UKBTS/SRI Transfusion Evidence Library. Methodologic quality was assessed. The primary outcome measure was the effect of FP on survival. RESULTS: Twenty-one new trials were eligible for inclusion. These covered prophylactic and therapeutic FP use in liver disease, in cardiac surgery, for warfarin anticoagulation reversal, for thrombotic thrombocy- topenic purpura treatment, for plasmapheresis, and in other settings, including burns, shock, and head injury. The largest number of recent RCTs were conducted in cardiac surgery; meta-analysis showed no significant difference for FP use for the outcome of 24-hours post- operative blood loss (weighted mean difference, -35.24 mL; 95% confidence interval, -84.16 to 13.68 mL). Overall, there was no significant benefit for FP use across all the clinical conditions. Only two of the 21 trials fulfilled all the criteria for quality assessment. CONCLUSION: Combined with the 2004 review, 80 RCTs have investigated FP with no consistent evidence of significant benefit for prophylactic and therapeutic use across a range of indications evaluated. There has been little improvement in the overall methodologic quality of RCTs conducted in the past few years. A recurring theme for transfusion of plasma is variation in practice and uncertainty around the evidence-based indications informing appropriate use. Plasma for transfusion is given primarily for two indications: to prevent bleeding (prophylaxis) or to stop bleeding (therapeutic). Clinical use of frozen plasma (FP) continues to grow, despite a number of publications attesting to questionable practice in many settings. Plasma continues to be commonly used as prophylaxis, before surgery or invasive procedures. Results from a large multicenter prospective observa- tional study in adult critical care, which evaluated just under 2000 admissions, showed that 30% of intensive care unit (ICU) patients had prolongation of prothrombin time (PT) during their admission 1,2 and that one-third of patients in adult critical care with PT prolongation received fresh-frozen plasma (FFP), but approximately 50% of patients received FFP in the absence of evidence of clinical bleeding. In the United States, the latest data from the National Blood Collection and Utilization Survey showed that 5,700,000 units of plasma were produced for transfusion in 2009. This represented a 0.3% increase from 2006 and a significant (23%) increase from 2005. 3 In 2004, in parallel to the drafting of guidelines for the use of FFP, cryoprecipitate, and cryosupernatant by the ABBREVIATIONS: CPB = cardiopulmonary bypass; FP = frozen plasma; ICU = intensive care unit; INR = international normal- ized ratio; PCC = prothrombin complex concentrate; PCT-FP = photochemically treated frozen plasma; PT = prothrombin time; PTT = partial thromboplastin time; RCT(s) = randomized con- trolled trial(s); TTP = thrombotic thrombocytopenic purpura. From NHS Blood and Transplant, Oxford, UK; Addenbrooke’s Hospital, Cambridge, UK; and the UK Cochrane Centre, Oxford, UK. Address reprint requests to: Simon Stanworth, Department of Transfusion Medicine, NHSBT, Level 2, John Radcliffe Hospital, Headington, Oxford, OX3 9BQ, UK; e-mail: simon. stanworth@nhsbt.nhs.uk. Received for publication October 5, 2011; revision received November 15, 2011, and accepted November 15, 2011. doi: 10.1111/j.1537-2995.2011.03515.x TRANSFUSION 2012;52:1673-1686. Volume 52, August 2012 TRANSFUSION 1673