Fibrinogen Levels during Catheter-Directed Thrombolysis for Acute PE

Evaluation of Fibrinogen Levels during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism

Clinical question
How are plasma fibrinogen level (PFL) affected by catheter-directed thrombolysis (CDT) in the setting of acute pulmonary embolism (PE) and is PFL associated with hemorrhagic complications in this setting?

Take-away point
CDT significantly decreases PFL, but is not associated with hemorrhagic complications.

Reference
Graif A, Grilli CJ, Kimbiris G, Paik HH, Leung DA. Evaluation of Fibrinogen Levels during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism. J Vasc Interv Radiol. 2020;31(8):1281-1289. doi:10.1016/j.jvir.2020.04.032

Click here for abstract

Study design
Retrospective, single-institution cohort study of 147 patients undergoing CDT for acute massive and submassive PE.

Funding source
No reported funding 

Setting
Private hospital network, Christiana Care Health System, USA.






Figure. Visual synopsis summarizing of study design and main results.

Summary

Catheter-directed thrombolysis (CDT) with tissue plasminogen activator (tPA) for acuate pulmonary embolism (PE) is thought to mitigate, although not eliminate, hemorrhagic risk compared to systemic thrombolysis. Some clinicians monitor plasma fibrinogen level (PFL) to anticipate hemorrhage, but supportive evidence is lacking. The authors performed a retrospective study of 147 cases of CDT for acute PE and evaluated PFL and its relationship with hemorrhagic complications.

Patients included in the study were adults presenting with acute massive or submassive PE who received either conventional catheter-directed thrombolysis (CCDT) or ultrasound-accelerated thrombolysis (USAT). Patients were excluded if presenting symptoms were >14 days, chronic PE was evident on CTA, or systemic tPA had been given prior to CDT. All patients received systemic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH).

Primary endpoints included change in initial and final PFL (with subgroup analyses of CCDT vs USAT and UFH vs LMWH groups) and PFL nadir. Secondary endpoints included correlation between PE severity metrics with PFL as well as tPA infusion rate, duration, and total dose.

A total of 147 cases met criteria with 98 undergoing CCDT, 34 undergoing USAT, and 15 undergoing a combination of both (excluded from CCDT vs USAT subgroup analysis). Anticoagulation was achieved with UFH in 102 cases and LMWH in 45 cases. Primary results showed a significant mean decrease from initial PFL to final PFL (-15.1 ± 69.4 mg/dl, p=0.007) and a PFL nadir of 327.6 ± 107.1 mg/dl.

Subgroup analyses did not reveal a significant difference in initial or final PFL between patients receiving UFH or LMWH; although, PFL nadir was significantly lower in the UFH group (313.7 ± 97.4 mg/dl, p= 0.03). No significant difference in initial, final or nadir PFL levels was detected between CCDT and USAT groups. In the CCDT group, there was a significant decrease in initial and final PFL (-14.9 ± 60.9 mg/dl, p=0.01) compared to the USAT group, which showed a nonsignificant increase in initial and final PFL. Secondary endpoint results showed no significant correlation between PE severity indices and any PFL or infusion metrics.

Six hemorrhagic complications were observed with no significant difference in change in PFL or between final PFL, PFL nadir, or change in PFL compared to cases without hemorrhagic complication.

The authors discuss that although there was a significant decrease in PFL during CDT for acute PE, this did not translate to clinical significance as PFL did not reach commonly used thresholds for modification or discontinuation of CDT. Two other, smaller studies evaluating PFL during CDT found similar decreases in PFL, although did not evaluate hemorrhagic complications. One study found a moderate positive correlation between PFL nadir and PE severity, which conflicts with the nonsignificant results from the current study.

Commentary

The authors evaluate PFL in a relatively large cohort of patients undergoing CDT. The larger sample size compared to previously published studies offers increased confidence in the main conclusion that PFL is significantly decreased in this population. However, they discuss that their study was insufficiently powered to evaluate the relationship between PFL and hemorrhagic complications given the very small number of total hemorrhagic complications (n=6). Additionally, the retrospective nature of this study inherently introduces inconsistencies and confounds, which can be amplified in the smaller subgroup analyses. Despite a significant primary endpoint, more data are needed to fully explore the relationship between PFL and hemorrhagic complications in this subgroup of patients receiving CDT for acute PE before any changes to clinical management can be made confidently.

Post Author
Catherine (Rin) Panick, MD
Resident Physician, Integrated Interventional Radiology
Dotter Interventional Institute
Oregon Health & Science University

@MdPanick