1.
Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures
Huber J, Stanworth SJ, Doree C, Fortin PM, Trivella M, Brunskill SJ, Hopewell S, Wilkinson KL, Estcourt LJ
The Cochrane database of systematic reviews. 2019;11:Cd012745
Abstract
BACKGROUND In the absence of bleeding, plasma is commonly transfused to people prophylactically to prevent bleeding. In this context, it is transfused before operative or invasive procedures (such as liver biopsy or chest drainage tube insertion) in those considered at increased risk of bleeding, typically defined by abnormalities of laboratory tests of coagulation. As plasma contains procoagulant factors, plasma transfusion may reduce perioperative bleeding risk. This outcome has clinical importance given that perioperative bleeding and blood transfusion have been associated with increased morbidity and mortality. Plasma is expensive, and some countries have experienced issues with blood product shortages, donor pool reliability, and incomplete screening for transmissible infections. Thus, although the benefit of prophylactic plasma transfusion has not been well established, plasma transfusion does carry potentially life-threatening risks. OBJECTIVES To determine the clinical effectiveness and safety of prophylactic plasma transfusion for people with coagulation test abnormalities (in the absence of inherited bleeding disorders or use of anticoagulant medication) requiring non-cardiac surgery or invasive procedures. SEARCH METHODS We searched for randomised controlled trials (RCTs), without language or publication status restrictions in: Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 7); Ovid MEDLINE (from 1946); Ovid Embase (from 1974); Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCOHost) (from 1937); PubMed (e-publications and in-process citations ahead of print only); Transfusion Evidence Library (from 1950); Latin American Caribbean Health Sciences Literature (LILACS) (from 1982); Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (Thomson Reuters, from 1990); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Search Platform (ICTRP) to 28 January 2019. SELECTION CRITERIA We included RCTs comparing: prophylactic plasma transfusion to placebo, intravenous fluid, or no intervention; prophylactic plasma transfusion to alternative pro-haemostatic agents; or different haemostatic thresholds for prophylactic plasma transfusion. We included participants of any age, and we excluded trials incorporating individuals with previous active bleeding, with inherited bleeding disorders, or taking anticoagulant medication before enrolment. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS 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. AUTHORS' CONCLUSIONS 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.
2.
Plasma transfusions prior to lumbar punctures and epidural catheters for people with abnormal coagulation
Estcourt LJ, Desborough MJ, Doree C, Hopewell S, Stanworth SJ
The Cochrane Database of Systematic Reviews. 2017;((9)):CD012497.
Abstract
BACKGROUND The insertion of a lumbar puncture needle or epidural catheter may be associated with peri- and post-procedural bleeding. People who require this procedure may have disorders of coagulation as a result of their underlying illness, co-morbidities or the effects of treatment. Clinical practice in some institutions is to mitigate the risk of bleeding in these patients by prophylactically transfusing plasma in order to correct clotting factor deficiencies prior to the procedure. However, plasma transfusion is not without risk, and it remains unclear whether this intervention is associated with reduced rates of bleeding or other clinically-meaningful outcomes. OBJECTIVES To assess the effect of different prophylactic plasma transfusion regimens prior to insertion of a lumbar puncture needle or epidural catheter in people with abnormal coagulation. SEARCH METHODS We searched for randomised controlled trials (RCTs), non-randomised controlled trials (non-RCT) and controlled before-after studies (CBAs) in CENTRAL (the Cochrane Library 2016, Issue 11), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and five other electronic databases as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) for ongoing trials to 9 January 2017. SELECTION CRITERIA We planned to include RCTs, non-RCTs, and CBAs involving transfusions of plasma given to prevent bleeding in people of any age with a coagulopathy requiring insertion of a lumbar puncture needle or epidural catheter. If identified, we would have excluded uncontrolled studies, cross-sectional studies and case-control studies. We would only have included cluster-RCTs, non-randomised cluster trials, and CBAs with at least two intervention sites and two control sites. In studies with only one intervention or control site, the intervention (or comparison) is completely confounded by study site making it difficult to attribute any observed differences to the intervention rather than to other site-specific variables.We planned to exclude people with haemophilia as they should be treated with the appropriate factor concentrate. We also planned to exclude people on warfarin as guidelines recommend the use of prothrombin complex concentrate for emergency reversal of warfarin. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We identified no completed or ongoing RCTs, non-RCTs, or CBAs. AUTHORS' CONCLUSIONS There is no evidence from RCTs, non-RCTs, and CBAs to determine whether plasma transfusions are required prior to insertion of a lumbar puncture needle or epidural catheter, and, if plasma transfusions are required, what is the degree of coagulopathy at which they should be given. We would need to design a study with at least 47,030 participants to be able to detect an increase in the number of people who had bleeding after lumbar puncture or epidural anaesthetic from 1 in 1000 to 2 in 1000.
3.
Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials
Stanworth SJ, Brunskill SJ, Hyde CJ, McClelland DL, Murphy MF
British Journal of Haematology. 2004;126((1):):139-152.
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Abstract
Summary: Randomized controlled trials of good quality are a recognized means to robustly assess the efficacy of interventions in clinical practice. A systematic identification and appraisal of all randomized trials involving fresh frozen plasma (FFP) has been undertaken in parallel to the drafting of the updated British Committee for Standards in Haematology guidelines on the use of FFP. A total of 57 trials met the criteria for inclusion in the review. Most clinical uses of FFP, currently recommended by practice guidelines, are not supported by evidence from randomized trials. In particular, there is little evidence for the effectiveness of the prophylactic use of FFP. Many published trials on the use of FFP have enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials include the dose of FFP used, and the potential for bias. No studies have taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. There is a need to consider how best to develop new trials to determine the efficacy of FFP in different clinical scenarios to provide the evidence base to support national guidelines for transfusion practice. Trials of modified FFP (e.g. pathogen inactivated) are of questionable value when there is little evidence that the standard product is an effective treatment.
PICO Summary
Population
Patients enrolled in randomised controlled trials (RCTs) for different types of fresh frozen plasma (FFP) usage, (57 RCTs).
Intervention
Fresh frozen plasma.
Comparison
Various comparators, including: no FFP/plasma; a non-blood product; a different blood product; different formulations of FFP.
Outcome
Most clinical uses of FFP, recommended by practice guidelines, were not supported by evidence from randomized trials. In particular, there was little evidence for the effectiveness of the prophylactic use of FFP. Many published trials on the use of FFP enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials included the dose of FFP used, and the potential for bias. No studies took adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP.