CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(01): 040-053
DOI: 10.1055/s-0042-1758653
Coagulation and Fibrinolysis

3-Factor versus 4-Factor Prothrombin Complex Concentrates for the Reversal of Vitamin K Antagonist-Associated Coagulopathy: A Systematic Review and Meta-analysis

Dorothea Puchstein
1   Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
Felix Kork
1   Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
Herbert Schöchl
2   Department for Anaesthesiology and Intensive Care Medicine, AUVA Trauma Academic Teaching Hospital, Paracelsus Medical University Salzburg, Salzburg, Austria
Farahnaz Rayatdoost
1   Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
Oliver Grottke
1   Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
› Author Affiliations
Funding None.


Long-term anticoagulation is used worldwide to prevent or treat thrombotic events. Anticoagulant therapy using vitamin K antagonists (VKAs) is well established; however, anticoagulants carry an increased risk of potentially life-threatening bleeding. In cases of bleeding or need for surgery, patients require careful management, balancing the need for rapid anticoagulant reversal with risk of thromboembolic events. Prothrombin complex concentrates (PCCs) replenish clotting factors and reverse VKA-associated coagulopathy. Two forms of PCC, 3-factor (3F-PCC) and 4-factor (4F-PCC), are available. Using PRISMA methodology, we systematically reviewed whether 4F-PCC is superior to 3F-PCC for the reversal of VKA-associated coagulopathy. Of the 392 articles identified, 48 full texts were reviewed, with 11 articles identified using criteria based on the PICOS format. Data were captured from 1,155 patients: 3F-PCC, n = 651; 4F-PCC, n = 504. ROBINS-I was used to assess bias. Nine studies showed international normalized ratio (INR) normalization to a predefined goal, ranging from ≤1.5 to ≤1.3, following PCC treatment. Meta-analysis of the data showed that 4F-PCC was favorable compared with 3F-PCC overall (odds ratio [OR]: 3.50; 95% confidence interval [CI]: 1.88–6.52, p < 0.0001) and for patients with a goal INR of ≤1.5 or ≤1.3 (OR: 3.45; 95% CI: 1.42–8.39, p = 0.006; OR: 3.25; 95% CI: 1.30–8.13, p = 0.01, respectively). However, heterogeneity was substantial (I 2 = 62%, I 2 = 70%, I 2 = 64%). Neither a significant difference in mortality (OR: 0.72; 95% CI: 0.42–1.24, p = 0.23) nor in thromboembolisms was reported. These data suggest that 4F-PCC is better suited than 3F-PCC for the treatment of patients with VKA-associated coagulopathy, but further work is required for a definitive recommendation.

Publication History

Received: 09 August 2022

Accepted: 23 September 2022

Article published online:
10 January 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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