Abstract: We included five trials in this review, all were conducted in high-income countries. Three additional trials are ongoing. One trial compared fresh frozen plasma (FFP) transfusion with no transfusion given. One trial compared FFP or platelet transfusion or both with neither FFP nor platelet transfusion given. One trial compared FFP transfusion with administration of alternative pro-haemostatic agents (factors II, IX, and X followed by VII). One trial compared the use of different transfusion triggers using the international normalised ratio measurement. One trial compared the use of a thromboelastographic-guided transfusion trigger using standard laboratory measurements of coagulation. Four trials enrolled only adults, whereas the fifth trial did not specify participant age. Four trials included only minor procedures that could be performed by the bedside. Only one trial included some participants undergoing major surgical operations. Two trials included only participants in intensive care. Two trials included only participants with liver disease. Three trials did not recruit sufficient participants to meet their pre-calculated sample size. Overall, the quality of evidence was low to very low across different outcomes according to GRADE methodology, due to risk of bias, indirectness, and imprecision. One trial was stopped after recruiting two participants, therefore this review's findings are based on the remaining four trials (234 participants). When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in 30-day mortality (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.13 to 1.10; very low-quality evidence). We are very uncertain whether there was a difference in major bleeding within 24 hours (1 trial comparing FFP transfusion vs no transfusion, 76 participants; RR 0.33, 95% CI 0.01 to 7.93; very low-quality evidence; 1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; RR 1.59, 95% CI 0.28 to 8.93; very low-quality evidence). We are very uncertain whether there was a difference in the number of blood product transfusions per person (1 trial, 76 participants; study authors reported no difference; very low-quality evidence) or in the number of people requiring transfusion (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; study authors reported no blood transfusion given; very low-quality evidence) or in the risk of transfusion-related adverse events (acute lung injury) (1 trial, 76 participants; study authors reported no difference; very low-quality evidence). When plasma transfusion was compared with other pro-haemostatic agents, we are very uncertain whether there was a difference in major bleeding (1 trial; 21 participants; no events; very low-quality evidence) or in transfusion-related adverse events (febrile or allergic reactions) (1 trial, 21 participants; RR 9.82, 95% CI 0.59 to 162.24; very low-quality evidence). When different triggers for FFP transfusion were compared, the number of people requiring transfusion may have been reduced (for overall blood products) when a thromboelastographic-guided transfusion trigger was compared with standard laboratory tests (1 trial, 60 participants; RR 0.18, 95% CI 0.08 to 0.39; low-quality evidence). We are very uncertain whether there was a difference in major bleeding (1 trial, 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence) or in transfusion-related adverse events (allergic reactions) (1 trial; 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence). Only one trial reported 30-day mortality. No trials reported procedure-related harmful events (excluding bleeding) or quality of life. Review findings show uncertainty for the utility and safety of prophylactic FFP use. This is due to predominantly very low-quality evidence that is available for its use over a range of clinically important outcomes, together with lack of confidence in the wider applicability of study findings, given the paucity or absence of study data in settings such as major body cavity surgery, extensive soft tissue surgery, orthopaedic surgery, or neurosurgery. Therefore, from the limited RCT evidence, we can neither support nor oppose the use of prophylactic FFP in clinical practice.

Plain-language summary: We included five trials which were all conducted in high-income countries. Our search is current up until 28 January 2019. One trial compared plasma transfusion with no transfusion given. Another trial compared plasma or platelet transfusion or both with neither plasma nor platelet transfusion given. One trial compared plasma transfusion with alternative products given to help blood clot. Another trial compared different blood tests to trigger a plasma transfusion, and still another trial compared different transfusion triggers using the same blood test. Four trials involved adult participants over 18 years old, and the fifth trial did not specify age of participants. In four trials, participants underwent bedside procedures. Only one trial involved some participants undergoing major surgical operations. Two trials included only participants in intensive care, and two trials included only participants with liver disease. One trial recruited only two participants. Therefore review results include the remaining four trials, incorporating 234 participants. Three further trials are ongoing. When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in major bleeding, number of blood transfusions per participant, or harmful effects from the transfusion (1 trial; very low-quality evidence). When plasma or platelet transfusion or both were compared with neither plasma nor platelet transfusion, we are very uncertain whether there was a difference in mortality within 30 days, or in the number of individuals requiring a transfusion (1 trial; very low-quality evidence). When plasma transfusion was compared with other haemostatic agents, we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion (1 trial; very low-quality evidence). When different triggers for plasma transfusion were compared (1 trial; 60 participants), we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion due to very low-quality evidence for these outcomes. The number of people requiring blood products may have been reduced overall, although this is based on low-quality evidence. No trials reported procedure-related harmful events or quality of life as an outcome. The overall quality of the evidence was predominantly very low over a range of clinically important outcomes due to combinations of issues within the studies, such as potential for bias, limited clinical settings, and imprecise estimates of intervention effects. We are very uncertain of the effectiveness and safety of the use of plasma in non-cardiac operations or invasive procedures due to very low-quality evidence. Furthermore, as trials do not cover a wide range of surgical contexts, our confidence in applying study results to the wider surgical setting is limited. Overall limited evidence for the utility of plasma transfused to people within this context is of insufficient quality to support or oppose its use.