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Meta-Analysis
. 2013 Aug 29;2013(8):CD008864.
doi: 10.1002/14651858.CD008864.pub2.

Fibrinogen concentrate in bleeding patients

Anne Wikkelsø  1 , Jens Lunde, Mathias Johansen, Jakob Stensballe, Jørn Wetterslev, Ann Merete Møller, Arash Afshari
Affiliations
Meta-Analysis

Fibrinogen concentrate in bleeding patients

Anne Wikkelsø et al. Cochrane Database Syst Rev. .

Abstract

Background: Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic deficiencies in several countries, but evidence is lacking regarding indications, dosing, efficacy and safety.

Objectives: We assessed the benefits and harms of fibrinogen concentrate compared with placebo or usual treatment for bleeding patients.

Search methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (1950 to 9 August 2013); EMBASE (1980 to 9 August 2013); International Web of Science (1964 to 9 August 2013); CINAHL (1980 to 9 August 2013); LILACS (1982 to 9 August 2013); and the Chinese Biomedical Literature Database (up to 10 November 2011), together with databases of ongoing trials. We contacted trial authors, authors of previous reviews and manufacturers in the field.

Selection criteria: We included all randomized controlled trials (RCTs), irrespective of blinding or language, that compared fibrinogen concentrate with placebo/other treatment or no treatment in bleeding patients, excluding neonates and patients with hereditary bleeding disorders.

Data collection and analysis: Three review authors independently abstracted data; we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effects of fibrinogen concentrate in adults and children in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of intervention on dichotomous outcomes as risk ratios (RRs) and on continuous outcomes as mean differences, with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis.

Main results: We included six RCTs with a total of 248 participants; none of the trials were determined to have overall low risk of bias. We found 12 ongoing trials, from which we were unable to retrieve any data. Only two trials provided data on mortality, and one was a zero event study; thus the meta-analysis showed no statistically significant effect on overall mortality (2.6% vs 9.5%, RR 0.28, 95% CI 0.03 to 2.33). Our analyses on blood transfusion data suggest a beneficial effect of fibrinogen concentrate in reducing the incidence of allogenic transfusions (RR 0.47, 95% CI 0.31 to 0.72) but show no effect on other predefined outcomes, including adverse events such as thrombotic episodes.

Authors' conclusions: In the six available RCTs of elective surgery, fibrinogen concentrate appears to reduce transfusion requirements, but the included trials are of low quality with high risk of bias and are underpowered to detect mortality, benefit or harm. Furthermore, data on mortality are lacking, heterogeneity is high and acute or severe bleeding in a non-elective surgical setting remains unexplored. Currently, weak evidence supports the use of fibrinogen concentrate in bleeding patients, as tested here in primarily elective cardiac surgery. More research is urgently needed.

PubMed Disclaimer

Conflict of interest statement

The authors of this protocol are involved in the preparation of a potentially eligible study: Fibrinogen concentrate for postpartum haemorrhage (Wikkelsoe 2011). This study is unrelated and is not sponsored by any groups or companies with economic interests.

No other conflicts of interests.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Trial sequential analysis of the effect of fibrinogen concentrate on the proportion of participants transfused using a control event proportion of 76% found in the included trials cumulated control groups. The diversity (58%) adjusted required information size for an anticipated intervention effect of 28% derived from the upper confidence limit of the RR (0.31 to 0.72) estimated in the traditional meta‐analysis is 374. The trial sequential monitoring boundary for benefit is crossed indicating lack of random error for the conclusion of an effect of 28% relative risk reduction even though the required information size has not been reached. However, risk of bias may have overestimated the intervention effect in the traditional meta‐analysis, so the results shall be interpreted with caution.
1.1
1.1. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 1 Mortality longest follow‐up.
1.2
1.2. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 2 ICU stay (hours).
1.3
1.3. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 3 Duration of mechanical ventilation (hours).
1.4
1.4. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 4 Stay in hospital (days).
1.5
1.5. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 5 Incidence of allogenic blood transfusion (types of comparison).
1.6
1.6. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 6 Incidence of allogenic blood transfusion (cardiac vs non‐cardiac).
1.7
1.7. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 7 Incidence of allogenic blood transfusion (pediatric vs adult).
1.8
1.8. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 8 Incidence of allogenic blood transfusion (high dose > 50 mg/kg vs low dose).
1.9
1.9. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 9 Re‐operation due to persistent bleeding.
1.10
1.10. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 10 Incidence of RBC transfusion longest follow‐up.
1.11
1.11. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 11 Thrombotic episodes (arterial and venous graft occlusion, pulmonary embolus, deep venous thrombosis).
1.12
1.12. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 12 Complications not specific to trial intervention (pleural effusion, abdominal ischaemia and other serious adverse events).
1.13
1.13. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 13 Blood loss/drainage, longest follow‐up.
1.14
1.14. Analysis
Comparison 1 Fibrinogen concentrate versus any comparator, Outcome 14 Blood loss/Drainage (24 hours) mL/kg/h.
2.1
2.1. Analysis
Comparison 2 Fibrinogen versus placebo or no treatment, Outcome 1 Incidence of allogenic blood transfusion (cardiac vs non‐cardiac).
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Update of

  • doi: 10.1002/14651858.CD008864

References

References to studies included in this review

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References to studies awaiting assessment

Galas 2012a {published data only}
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References to ongoing studies

Fries 2011 {published data only}
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Haas 2012 {published data only}
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