Original Article
Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: An open, prospective randomized controlled trial

https://doi.org/10.1016/j.thromres.2005.08.005Get rights and content

Abstract

Prothrombin Complex Concentrate (PCC) is indicated for the acute reversal of oral anticoagulation therapy. To compare the efficacy of a “standard” dosage of 20 ml PCC equivalent to about 500 IU factor IX (group A), and an “individualized” dosage based on a target-INR of 2.1 or 1.5, the initial-INR and the patient's body weight (group B), we performed an open, prospective, randomized, controlled trial. The in vivo response and in vivo recovery of factor II, VII, IX and X in these patients on oral anticoagulation was determined.

Ninety three patients (group A: 47; group B: 46) with major bleedings or admitted for urgent (surgical) interventions were enrolled. PCC and Vitamin K (10 mg) were administered intravenously. We evaluated the effect of treatment by the decrease of INR and the clinical outcome. The number of patients reaching the target-INR 15 min after the dosage of PCC was significantly higher in the group treated with an “individualized” dosage, compared to the group treated with a standard dose, (89% versus 43%; p < 0.001).

So, we conclude that for the acute reversal of oral anticoagulant therapy, an “individualized” dosage regimen of PCC based on the target-INR, the initial-INR, and body weight of the patient, is significantly more effective in reaching the target-INR than a “standard” dosage.

The in vivo response and in vivo recovery found in this study was higher then in patients with isolated factor deficiencies. This suggests that the pharmacokinetics in patients on oral anticoagulants may be different.

Section snippets

Material

Prothrombin complex concentrate (Cofact®, licensed in the Netherlands under RVG 17060, Sanquin, Amsterdam, The Netherlands) is manufactured from human plasma obtained from selected, voluntary, non-remunerated donors. Each donation has been tested and found negative for HIV 1–2, HBV, HCV, and HTLV I/II and treponema pallidum by serological and/or NAT testing methods. Virus reducing steps are incorporated in the production process, i.e., a solvent detergent virus inactivation step, as well as a

Results

In this open, prospective, randomized, controlled trial, all 93 patients were included in the intention-to-treat analysis. The characteristics of the patients of group A and B were found to be similar in sex, age, bodyweight, body mass index, number of bleedings and interventions, and the initial-INR and target-INR (Table 2).

For reaching the target-INR at 15 min after the first dosage of PCC, a statistically significant difference was found in the number of patients receiving the individualized

Discussion

In this study, a “standard” dosage of 20 ml PCC is compared with an individualized dosing based on the patient's initial-INR, the target-INR and bodyweight. The 20 ml dosage was the volume of PCC that is regularly being used, like in the hospital where the study was performed. Of the patients treated according to the individualized dosing regimen, significantly more patients attained the target-INR 15 min after administration of PCC, i.e., 89% versus 43% of patients treated with a standard dose.

Acknowledgments

The statistical analysis was performed by H.E. Nienhuis; J.C. Drenth contributed to earlier versions of this article.

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