Interpretation
Interestingly, in the OBS2 study, fibrinogen was administered after immediate estimation of fibrinogen levels using the Rotem viscoelastomeric point-of-care test 17. A nearly two-fold decrease in total allogenic blood product transfusion rate was observed in women with plasma fibrinogen concentrations estimated below 2.0 g/L and supplemented with fibrinogen. The difference was not significant however due to a lack of power. Our study and its negative results further contributes to the attractiveness of rapid plasma fibrinogen assays for initiating and guiding treatment when necessary,i.e. only in the most severe cases associated with coagulopathy and low fibrinogen levels 15.
Thus, three major randomized and well conducted controlled studies, FIB-PPH, OBS2 and FIDEL, all found that early fibrinogen replacement is not beneficial in the course of severe PPH management when a second line uterotonic agent is needed after prostaglandins and when plasma fibrinogen level is not known. Nonetheless, several other and older observational studies or reports from the UK, Japan, or Turkey still maintain that fibrinogen supplementation is effective and beneficial14,28-32. This is not surprising, as most patients in those studies presented very severe and advanced PPH, and much greater blood loss and much lower plasma fibrinogen concentrations (usually < 1 g/L) than those reported in the randomized studies. Although the patients received numerous transfusions (including fresh frozen plasma, FFP) and were not compared with adequate control groups, the studies documented safety and established the usefulness of massive doses of fibrinogen (up to 8 g) to avoid FFP transfusion, fluid overload, and for rapid correction of very low fibrinogen levels. Although the randomized controlled trial is the gold standard methodology for demonstrating the efficacy of a therapeutic strategy, it is not always adapted to field constraints, especially in life-threatening emergencies. In light of this, observational or uncontrolled studies provide potentially biased, but better targeted data, which are truly informative and complementary to those of randomized controlled trials.
Altogether, these studies back the use of a targeted strategy to adjust the supplementation to the fibrinogen level estimation. Because fibrinogen decrease may be drastic in PPH 33,34, and because a prompt therapeutic answer is expected, newly available “plug-and-play” viscoelastometry bedside devices allowing a quick and convenient assay in the emergency room are very useful tools. This approach can help clinicians identify coagulopathies in “real-time” and when emergency fibrinogen supplementation is required, especially in severe cases of PPH, or in specific situations such as placental abruption or amniotic fluid embolism 33,34.