Fixed-dose prothrombin complex concentrate for emergent warfarin reversal among patients with intracranial hemorrhage

Dietrich, Scott; Mixon, Mark; Rech, Megan A.

doi:10.1016/j.ajem.2021.06.032

Cited by 4 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 ; and Supplementary Table 2 , http://links.lww.com/CCM/H489 ). Three studies were prospective RCTs ( 8 – 10 ), one was a prospective cohort of both treatment regimens ( 29 ), two were prospective cohorts treated with a fixed-dose regimen compared with historical data ( 28 , 38 ), and the remainder were retrospective studies ( 13 , 14 , 16 , 17 , 25 – 27 , 30 , 32 , 34 , 39 – 41 ). All studies were conducted in the United States or The Netherlands.…”

Section: Resultsmentioning

confidence: 99%

“…Variable-dose regimens all followed the respective manufacturers’ recommendations. Four studies included only patients with ICH ( 27 , 30 , 32 , 39 ), whereas another three studies included subgroup analysis for ICH patients ( 17 , 25 , 34 ). ICH patients were specifically excluded from four studies ( 10 , 14 , 28 , 29 ).…”

Section: Resultsmentioning

confidence: 99%

“…Meta-analyses were conducted using the meta-package in R (http://CRAN.R-project.org/package=meta). For studies where continuous variables were reported as median and interquartile range (9,(25)(26)(27), or median and range (10,(28)(29)(30), conversion to mean and sd was performed using the methods described by Wan et al (31). In cases where continuous variables were presented as mean and 95% CI, the sd was computed using the Cochrane methodology as follows: sd = √n × (upper limit-lower limit)/4.128, where n represents the sample size (32,33).…”

Section: Statistical Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Alwakeal,

Maas,

Naidech

et al. 2024

Critical Care Medicine

View full text Add to dashboard Cite

Objectives: Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. Data Sources: A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. Study Selection: Abstracts and full texts were assessed independently and in duplicate by two reviewers. Data Extraction: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. Data Synthesis: The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. Conclusions: A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Alwakeal,

Maas,

Naidech

et al. 2024

Critical Care Medicine

View full text Add to dashboard Cite

show abstract

“…Warfarin is used in clinical practice since 1941 and has been frequently used as an anticoagulation in atrial fibrillation, venous thromboembolism, mechanical heart valves, and a variety of various other clinical settings. In fact, warfarin is one of the most widely prescribed drugs in the industrialized world, 35 with multiple recent reports also confirming this statement 36-41 . Warfarin causes anticoagulation by inhibiting the vitamin K epoxy reductase—the enzyme which is necessary for posttranslational carboxylation of many coagulation factors including factors II, VII, IX, and X as well as protein C and protein S 42 .…”

Section: Perspectivesmentioning

confidence: 97%

“…In fact, warfarin is one of the most widely prescribed drugs in the industrialized world, 35 with multiple recent reports also confirming this statement. [36][37][38][39][40][41] Warfarin causes anticoagulation by inhibiting the vitamin K epoxy reductase-the enzyme which is necessary for posttranslational carboxylation of many coagulation factors including factors II, VII, IX, and X as well as protein C and protein S. 42 Bleeding caused by warfarin is one of the most important which is associated with high morbidity and mortality. 43 It is one of the most reported serious adverse events that were reported in the 1990 s and 2000 s to the US Food and Drug Administration.…”

Section: Perspectivesmentioning

confidence: 99%

Application of fresh frozen plasma transfusion in the management of excessive warfarin-associated anticoagulation

Luo

2022

Blood Science

View full text Add to dashboard Cite

Warfarin is a commonly used oral anticoagulant. Patients with artificial valve replacement, atrial fibrillation, pulmonary embolism, deep vein thrombosis, and other diseases require long-term anticoagulant oral treatment with warfarin. As warfarin exhibits prompt action with long maintenance time, it has become a key drug for the treatment of patients at risk of developing thrombosis or thromboembolism. Warfarin is a bican coumarin anticoagulant, that exhibits competitive action against vitamin K as its mechanism of action, thereby inhibiting the synthesis of coagulation factors-predominantly the vitamin K-dependent coagulation factors II, VII, IX, and X-in hepatocytes. Long-term warfarin is known to significantly increase the risk of organ bleeding in some patients, while some patients may need to reverse the anticoagulation effect. For instance, patients scheduled for emergency or invasive surgery may require rapid anticoagulation reversal. During such medical circumstances, fresh frozen plasma (FFP) is clinically used for the reversal of excess warfarin-associated anticoagulation, as it contains all the coagulation factors that can alleviate the abnormal blood anticoagulation status in such patients. Accordingly, this article aims to perform an in-depth review of relevant literature on the reversal of warfarin with FFP, and insightful deliberation of the application and efficacy of this clinical intervention.

show abstract

UpdatED: The emergency medicine pharmacotherapy literature of 2022

Sarangarm¹,

Zimmerman²,

Faine³

et al. 2023

The American Journal of Emergency Medicine

View full text Add to dashboard Cite

Fixed-dose prothrombin complex concentrate for emergent warfarin reversal among patients with intracranial hemorrhage

Cited by 4 publications

References 19 publications

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Application of fresh frozen plasma transfusion in the management of excessive warfarin-associated anticoagulation

UpdatED: The emergency medicine pharmacotherapy literature of 2022

Contact Info

Product

Resources

About