Modified version of the American College of Cardiology's recommendation for low-dose prothrombin complex concentrate is effective for warfarin reversal

Gilbert, Brian W.; Morton, Lauren; Huffman, Joel B.; Roemer, Kaleb; Potter, A.; Cassidy, Christopher D.; Vasquez, Donald G.

doi:10.1016/j.ajem.2019.12.005

Cited by 15 publications

(17 citation statements)

References 13 publications

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“…There was no significant difference between treatment groups in number of patients achieiving INR <1.6 or <1.4 following 4F-PCC infusion. 31…”

Section: Resultsmentioning

confidence: 99%

“…There was no significant difference between treatment groups in number of patients achieiving INR <1.6 or <1.4 following 4F-PCC infusion. 31 Use of doses 50 IU/kg. While results from these studies generally support fixed dosing with !1000 IU 4F-PCC if the baseline INR for reversal is >2, few data have been published on 4F-PCC for reversal in patients with baseline INRs <2; there is currently no indicated dose of Kcentra for this particular population.…”

Section: Alternative Dosing Strategiesmentioning

confidence: 99%

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Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Rhoney

Chester

Darsey

2020

Clin Appl Thromb Hemost

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Expert consensus and international guidelines recommend urgent co-administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) to rapidly reverse VKA-related bleeding. This narrative review examined real-world evidence and strategies to optimize international normalized ratio (INR) reversal, hemostasis, and outcomes in patients receiving 4F-PCC in this setting. Key determinants for success include the appropriate use of alternative dosing and administration strategies, such as fixed dosing and increased infusion speed, adherence to institutional guidelines, and removing significant institutional barriers to reduce time to treatment. In the opinion of authors, minimizing the time to treatment with 4F-PCCs is of paramount importance when treating patients with VKA-related bleeding. Practices that safely and feasibly shorten the time to administration should be included in guidelines for institutions responsible for anticoagulant care, and adhered to in centers that perform invasive procedures on patients receiving VKA therapy. Further studies are required to optimize use of 4F-PCC, particularly in relation to the ideal dosing strategy and the role of INR.

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“…There was no significant difference between treatment groups in number of patients achieiving INR <1.6 or <1.4 following 4F-PCC infusion. 31…”

Section: Resultsmentioning

confidence: 99%

Section: Alternative Dosing Strategiesmentioning

confidence: 99%

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Rhoney

Chester

Darsey

2020

Clin Appl Thromb Hemost

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“…1 Several studies have evaluated alternative dosing strategies, including indication-specific and various fixed-dose regimens. [2][3][4][5][6][7][8][9][10][11][12][13][14] An optimal dosing regimen would provide adequate anticoagulant reversal and decrease the risk of life-threatening thrombotic events while also offering the potential for significant cost savings and improved drug utilization in the era of drug shortages.…”

Section: Introductionmentioning

confidence: 99%

“…8,10 Whereas studies utilizing a fixed dose of 1500 units have displayed positive results, other studies have been published with differing fixed-dose regimens. 3,7,11 Current guidelines also recommend several dosing strategies: either the package insert dosing or a low fixed-dose option (1000 units for any major bleed or 1500 units for intracranial hemorrhage). 15 Given the wide variety of dosing protocols evaluated and recommended in the literature, additional studies are needed to determine which fixed-dose regimen is most effective and safe for patients requiring emergent warfarin reversal.…”

Section: Introductionmentioning

confidence: 99%

Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate

et al. 2020

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Background: Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. Objectives: The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. Methods: This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. Results: Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. Conclusion and Relevance: A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.

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“…Although we agree with the authors regarding the association, we beg to defer from the authors regarding its causation.Finally, a combined pharmacy-and physician-driven administration of 4F PCC is shown to improve the adequacy of administration, monitoring, cost of care, and outcome. 5,7,8 The involvement of a pharmacy and a pharmacy-driven protocol can reduce patient morbidity and cost of care by reducing avoidable administrations of this expensive agent. The pharmacy-driven protocol can also facilitate the administration of varying doses of 4F PCC as per the patient's requirement.…”

mentioning

confidence: 99%

Stroke Symptoms in a Patient on 4-Factor Prothrombin Complex

2020

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We read with interest the article "Ischemic stroke symptoms after warfarin reversal with 4-factor prothrombin complex concentrate case report" published by Carson and Price in your esteemed journal. The authors have excellently described an 83-year-old lady sustaining wrist injury, receiving 4-factor prothrombin complex concentrate (4F PCC) before surgery. The patient has had left-sided hemiparesis which was treated with tissue plasminogen activator with complete improvement in deficits. 1 The authors have administered 4F PCC at the dose of 25 units/kg anticipating the emergent surgery. Recently, multiple studies have demonstrated the efficacy of low-dose 4F PCC, even in patients requiring acute surgical intervention. 2,3 Administration of low-dose 4F PCC, at the dose of 15 units/ kg, has been shown to effectively reverse coagulopathy, with lesser reported thromboembolic events.To date, most of the studies have reported venous thromboembolic events after the administration of PCC. Attributing the administration of 4F PCC to the development of ischemic stroke as in this patient might not be causative. 4,5 Around 75 000 patients develop stroke while being admitted to the hospital in the United States. Risk factors of developing stroke in these patients are elevated diastolic blood pressure, atrial fibrillation, prosthetic heart valves, carotid stenosis, heart failure, and history of myocardial infarction. 4,6 As the authors have already mentioned, this patient has got significant risk factors that could solely attribute to the development of stroke. Although we agree with the authors regarding the association, we beg to defer from the authors regarding its causation.Finally, a combined pharmacy-and physician-driven administration of 4F PCC is shown to improve the adequacy of administration, monitoring, cost of care, and outcome. 5,7,8 The involvement of a pharmacy and a pharmacy-driven protocol can reduce patient morbidity and cost of care by reducing avoidable administrations of this expensive agent. The pharmacy-driven protocol can also facilitate the administration of varying doses of 4F PCC as per the patient's requirement. Author ContributionsAKM and AL were instrumental in data collection. AKM and KKS were involved in data analysis and manuscript writing. AKM and KKS were involved in formatting of the manuscript. AKM and AL were involved in editing and finalizing.

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Modified version of the American College of Cardiology's recommendation for low-dose prothrombin complex concentrate is effective for warfarin reversal

Cited by 15 publications

References 13 publications

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate

Stroke Symptoms in a Patient on 4-Factor Prothrombin Complex

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