Background: As oral factor Xa inhibitor (oFXaI) use has increased, so has publication of case series describing 4-factor prothrombin complex concentrate (4F-PCC) use to manage oFXaI-related bleeding.

Aims: To identify case series describing 4F-PCC to manage oFXaI-related bleeding and appraise their methodological and reporting quality.

Methods: We performed searches of Medline and Embase (01/01/2011-11/08/2019) to identify case series of ≥10-patients who experienced oFXaI-related major bleeding managed with 4F-PCC. Case series’ evaluation was performed using a validated tool adapted for this topic. The tool included items addressing patient selection (S1-5), bleed/outcome ascertainment (A1-8), causal/temporal association (C1-6) and reporting (R1-15). The percentage of series meeting each criterion (yes/+) is reported.

Results: We identified 11 case series. No series had ≥100-patients (range=13-84), three were performed prospectively, two detailed specific inclusion criteria (anticoagulant(s), time since anticoagulant dose, major bleeding restriction) and three noted consecutive patient inclusion (Figure 1). While nine series provided clear/appropriate methods for diagnosis of intracranial hemorrhage (ICH); none did so for extracranial bleeds, nor was it clear whether bleeding was adjudicated in any series. Hemostatic effectiveness, thrombosis and mortality were together evaluated in nine series, but only four used appropriate methods to evaluate/diagnosis hemostasis in ICH, five in gastrointestinal bleeds, four in other bleeds and one in thrombosis. Independent adjudication of hemostasis (n=1 series) and thrombosis (n=2 series) was infrequent. Longer-term ascertainment (≥30-days) for mortality and thrombosis was noted in five and six series, respectively. Anticoagulation measurement/levels in at least some patients were conveyed in three series. Few case series provided data on anticoagulant agent/dose (n=2), time from anticoagulant dose (n=4), time-to-reversal (n=5) or baseline (n=5) or change (n=0) in neurologic function (Figure 2).

Conclusions: Although many case series describing 4F-PCC for reversing oFXaI-related bleeding have been published, the presence of methodological flaws and/or poor reporting necessitates caution in interpretation.
Note: Funding by Portola Pharmaceuticals

[Figure 1. Methodological quality domains (assessed as yes, no, unclear or not applicable)]

[Figure 2. Reporting quality domains (assessed as yes or no)]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/methodological-and-reporting-quality-in-case-series-of-four-factor-prothrombin-complex-concentrate-in-the-management-of-oral-factor-xa-inhibitor-associated-bleeding/