An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies

Abstract

Background: Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting.

Design and methods: Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (< 2.0) after prothrombin complex concentrate treatment, and successful clinical outcome.

Results: Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed).

Conclusions: Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.

Figures

Figure 1.

INR before and after PCC treatment. Cohort 1: fixed dose, cohort 2: variable dose regimen. International Normalized Ratio (INR) at baseline and 15 min after PCC treatment. INRs are expressed as a number up to 7.6. INR was above 7.6 in 35% of patients in each cohort. Boxes span the interquartile range. Horizontal lines bisecting the boxes indicate median values and lower and upper error bars the range.

Figure 2.

PCC administration. Prothrombin Complex Concentrate (PCC) administered per patient. Graphic conventions as in figure 1. In cohort 1, median dosage is the same line as upper interquartile range. Cohort 1: fixed dose regimen, cohort 2: variable dose regimen.