Increased risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis

Following intravenous thrombolysis (IVT) for acute ischemic stroke, fibrinogen depletion dramatically raises the risk of symptomatic intracerebral hemorrhage (sICH) and severe bleeding, says an article published in the Journal of Stroke.

Intravenous thrombolysis for acute ischemic stroke can result in deadly consequences such as symptomatic intracerebral hemorrhage and significant bleeding. Therefore, Michele Romoli and colleagues carried out this research to find out how serious bleeding incidents are affected by early fibrinogen depletion following IVT.

In this observational multicenter prospective cohort research, 1678 patients had IVT for acute ischemic stroke at 6 Italian sites in a line, and their fibrinogen concentrations were measured at baseline, two hours after IVT, and six hours after IVT. After two hours following IVT, fibrinogen depletion was defined as a drop below 200 mg/dL or as a drop below 50% of baseline fibrinogen levels. The two main outcomes were sICH and significant bleeding, which was defined as lethal hemorrhage, a hemoglobin level drop of more than >2 g/dL/>1, more than one unit of transfusion, or bleeding at a critical location. The following outcomes were also observed: (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH as defined by ECASSII. A modified Rankin Scale score of 0 to 2 after three months was considered to be a good functional recovery.

The key findings of this study were:

1. Major bleeding (n=297) and sICH (n=116) were linked to a reduced rate of satisfactory functional recovery (P0.001) out of the 1678 patients included in the study.

2. Despite equal fibrinogen levels at admission, persons with sICH, significant bleeding, and all other bleeding outcomes had higher rates of fibrinogen depletion after 2 hours following IVT.

3. sICH and substantial bleeding were still significantly predicted by fibrinogen depletion in the backward stepwise multivariable logistic regression model.

4. Fibrinogen depletion may be responsible for 31% of sICH cases. Due of the increased risk of significant bleeding and sICH, there is a link between fibrinogen depletion and a poorer clinical outcome at 3 months following stroke (P=0.012).

In conclusion, fibrinogen depletion is a separate risk factor for bleeding, therefore regular evaluation may be taken into account to stratify the risk of ICH. Investigations into the reduction of bleeding risk require early fibrinogen repletion trials.

Reference: 

Romoli, M., Vandelli, L., Bigliardi, G., Naccarato, M., Moller, J., Balestrino, M., Giammello, F., Gentile, M., Dell'Acqua, M. L., Manganotti, P., Musolino, R. F., … Zini, A. (2022). Fibrinogen Depletion Coagulopathy Predicts Major Bleeding After Thrombolysis for Ischemic Stroke: A Multicenter Study. In Stroke. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/strokeaha.122.039652