Fixed- versus Variable-dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-analysis

Introduction: Four-factor prothrombin complex concentrate (4-PCC) is the recommended standard of care for acute vitamin K antagonist (VKA) reversal, but optimal dosing is unknown.

Methods: We searched the PubMed, MEDLINE (OVID), and Embase databases from January 2000 to December 2021 for clinical studies comparing fixed-dose versus variable-dose 4-PCC to reverse VKA with at least one reported clinical outcome. Treatment effects were expressed as odds ratios (OR) with 95% confidence intervals (CI) and pooled using a random-effects model.

Results: There were fifteen studies included, encompassing 1,762 patients. The Fixed-dose 4-PCC group had a lower death rate (OR=-0.3, 95 % CI -0.6 to -0.07, p=0.06). Additionally, there was a reduction in thromboembolic events (OR=-0.6, 95 % confidence CI -1.2 to 0.01, p=0.08). However, the Fixed-dose 4-PCC group achieved INR goals at a lower rate than the Variable-dose group, at INR 1.5 (OR= -0.5, 95 % CI -0.97 to -0.4, p= < .0001) and INR 2 (OR= -0.2, 95% CI -0.85 to -0.4, p= 0.46).

Conclusion : A fixed-dose of 4-PCC can be used effectively and safely to reverse VKAs in various clinical situations. However, further well-designed, controlled studies should be conducted to determine the optimal dose.