Plasma Fibrinogen Change as a Predictor of Major Bleeding During Catheter-Directed Thrombolysis.

Background: Our primary objective was to determine the relationship between plasma fibrinogen levels (PFLs) and major bleeding complications during catheter-directed thrombolysis, including final, nadir, and change over time. Furthermore, we sought to evaluate additional predictors of bleeding outcomes, including duration of lysis and total dose of tissue plasminogen activator received.

Methods: In this multicenter retrospective cohort study, we reviewed all patients undergoing catheter-directed thrombolysis between January 2016 and August 2021. Patients undergoing thrombolysis for management of peripheral arterial or venous thromboses, as well as for submassive pulmonary embolism, were included. We examined the relationships between PFLs during catheter-directed lysis and the incidence of major bleeding-that is significant hemorrhage requiring transfusion, intracranial hemorrhage, or hemorrhage requiring adjunctive procedures. We also examined the duration of lysis and total lytic agent dose received to assess for association with major bleeding.

Results: A total of 438 patients underwent catheter-directed lysis from January 1, 2016 through August 21, 2021, with a major bleeding rate of 16%. Patients who experienced major bleeding were more likely to be older (P = 0.022), experience in-stent thrombosis (P = 0.041), or have thrombosis in a lower extremity vessel (P = 0.011). There was no association between the incidence of major bleeding and a nadir PFL of <150 mg/dL (P = 0.194). Those who experienced major bleeding complications had a significantly greater decrease in PFL from baseline to nadir. This was true for both absolute (P = 0.029) and relative (P = 0.034) PFL decrease. Only percent decrease remained a significant predictor when adjusting for age, thrombosis type, and thrombosis location (P = 0.041). The PFL changes that were the best predictors of major bleeding complications were an absolute decrease of 146 mg/dL, or a relative decrease of 47%, giving a sensitivity and specificity of 71% and 48%, respectively. If neither were true, the negative predictive value for major bleeding was 89% regardless of absolute PFL.

Conclusions: In this large, multicenter cohort, there does not appear to be an association between absolute PFL and major bleeding during catheter-directed lysis. Specifically, the typical absolute threshold of < 150 mg/dL was not an independent predictor of major bleeding. There was an association between percent-change in plasma fibrinogen and major bleeding, which aligns with the underlying physiologic mechanism of fibrinogen degradation coagulopathy. Applying a so-called "50-150 Rule" to catheter-directed lysis may decrease bleeding complications. That is, continued lysis should be re-evaluated if PFL drops by ≥150 mg/dL or by ≥50% from baseline regardless of absolute PFL.