Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis.

Coagulopathy and severe bleeding are associated with high mortality. We evaluated haemostatic treatment guided by the functional viscoelastic haemostatic assays, thromboelastography or rotational thromboelastometry in bleeding patients. We searched for randomised, controlled trials irrespective of publication status, publication date, blinding status, outcomes published or language from date of inception to 5 January 2016 in six bibliographic databases. We included 17 trials (1493 participants), most involving cardiac surgery. Thromboelastography or rotational thromboelastometry seemed to reduce overall mortality compared to any of our comparisons (3.9% vs. 7.4%, RR (95% CI) 0.52 (0.28-0.95); I2 = 0%, 8 trials, 717 participants). However, the quality of evidence is graded as low due to the high risk of bias, heterogeneity, imprecision and low event rate. Thromboelastography or rotational thromboelastometry significantly reduced the proportion of patients transfused with red blood cells (RR (95% CI) 0.86 (0.79-0.94); I2 = 0%, 10 trials, 832 participants), fresh frozen plasma (RR (95% CI) 0.57 (0.33-0.96); I2 = 86%, 10 trials, 832 participants) and platelets (RR (95% CI) 0.73 (0.60-0.88); I2 = 0%, 10 studies, 832 participants). There was no difference in proportion needing surgical re-interventions (RR (95% CI) 0.75 (0.50-1.10); I2 = 0%, 9 trials, 887 participants). Trial sequential analysis of mortality suggests that only 54% of the required information size has been reached so far. Transfusion strategies guided by thromboelastography or rotational thromboelastometry may reduce the need for blood products in patients with bleeding, but the results are mainly based on trials of elective cardiac surgery involving cardiopulmonary bypass, with low-quality evidence.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Fibrinogen concentrate for bleeding--a systematic review.

Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies included a control group. Three out of 11 found a reduction in transfusion requirements while mortality was reduced in two and bleeding in one. In the available RCTs, which all have substantial shortcomings, we found a significant reduction in bleeding and transfusions requirements. However, data on mortality were lacking. Weak evidence from RCTs supports the use of fibrinogen concentrate in bleeding patients, primarily in elective cardiac surgery, but a general use of fibrinogen across all settings is only supported by non-randomised studies with serious methodological shortcomings. It seems pre-mature to conclude whether fibrinogen concentrate has a routine role in the management of bleeding and coagulopathic patients. More RCTs are urgently warranted.