Is It Time to Raise the Threshold for Critically Low Fibrinogen? Insights From a Retrospective, Consecutive-Case Cohort Study of Low Fibrinogen due to Various Causes.

INTRODUCTION: Fibrinogen deficiency is an important coagulation abnormality, with diverse causes. METHODS: A consecutive-case cohort study of adult and pediatric patients with low Clauss fibrinogen at four acute care hospitals was undertaken to explore findings, causes, and predictors of outcomes, including the optimal fibrinogen critical value to predict all-cause mortality. RESULTS: Over 11 months, 4.9% of tested patients (349/7183, after excluding n = 4 for preanalytical errors) had fibrinogen deficiency (63.6% male; 86.8% adult; 29.2% with liver disease; 14.0% with massive transfusion; 19.5% with fibrinogen < 1.0 g/L, the historical critical value; none with a diagnosed inherited deficiency). Primary causes of fibrinogen deficiency were: cardiovascular surgery (CVS); trauma; overt, not overt and potential/not scorable (no D-dimer results) disseminated intravascular coagulation (DIC); liver disease; acute bleeding; and other (including uncertain) causes. After Bonferroni correction, overt and potential/not scorable DIC were associated with significantly lower fibrinogen levels and higher mortality than most other causes were, particularly compared to trauma (p < 0.0001). Median time to death after diagnosing fibrinogen deficiency was 1 (IQR: < 1-7) day. A Clauss fibrinogen ≤ 1.3 g/L had optimal sensitivity and specificity for predicting mortality among fibrinogen-deficient patients, and multivariate analyses indicated it was a strong, independent predictor of death (adjusted odds ratio [95% confidence intervals]: 6.2 [2.9-13.6] vs. ≤ 3.6 for liver disease and DIC). Spearman correlation indicated that the nadir Clauss fibrinogen level had a negative correlation (r = -0.34, p < 0.0001) to the amount of fibrinogen replacement received. CONCLUSIONS: Low Clauss fibrinogen was commonly acquired and levels ≤ 1.3 g/L were optimal for predicting all-cause mortality.