SAFETY of PROTHROMBIN COMPLEX CONCENTRATES IN PATIENTS REQUIRING RAPID REVERSAL of ANTICOAGULANT TREATMENT with the VITAMIN K ANTAGONISTS: a Systematic Review and a Meta-Analysis of the Literature.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1113-1113
Author(s):  
Francesco Dentali ◽  
Chiara Marchesi ◽  
Matteo Giorgi Pierfranceschi ◽  
Mark A. Crowther ◽  
David Garcia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Vitamin K ◽  
Research Funding ◽  
Vitamin K Antagonists ◽  
Viral Transmission ◽  
Thromboembolic Events ◽  
Thromboembolic Complications ◽  
Review Of The Literature ◽  
Weighted Mean ◽  
Prothrombin Complex Concentrates

Abstract Abstract 1113 Background: Prothrombin complex concentrates (PCCs) are currently recommended by several international guidelines as the treatment of choice in warfarin-related coagulopathy. However, while the efficacy of PCCs is well established, their safety in terms of risk of thromboembolic complications, some of which may be severe or even life-threatening, is still not clear. Thus, we performed a systematic review of the literature with the aim of evaluating the rate of thromboembolic complications in patients on Vitamin K antagonists (VKAs) treated with PCCs for a bleeding event or before an urgent invasive procedure. Methods: MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on incidence thromboembolic complications in patients on VKAs were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose of PCC treatment. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Results: 28 studies for a total of 1104 patients were included in our systematic review. Seven studies used 3-factor PCCs, 21 studies used 4-factor PCCs. Concomitant vitamin K was administered in 21 studies, while fresh frozen plasma in 6. Seventeen patients had a thromboembolic complication after PCCs administration (weighted mean 1.9%; 95% CI 1.1–2.9 %). Of the thromboembolic events, 4 were fatal (23%). The incidence of thromboembolic events was 1.9%; (95% CI 1.0–3.1 %) in patients treated for bleeding and 0.8% (95% CI 0.1–2.0 %) in patients treated before urgent surgery or invasive procedures. For 5 of the reported events we were unable to define the subgroup. The incidence of thromboembolic events was 2.3% (95% CI 1.2–3.8) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. One hundred and seven patients died for a mean mortality rate of 11.1% (95% CI 6.4–17.0 %). Only 7 studies for a total 257 patients provided data on the incidence of viral transmission after PCCs administration. In this subgroup of patients there were 4 episode of positivity for parvovirus B19 for a mean incidence of 1.9% (95% CI 0.3–4.9%). Conclusions: The results of our systematic review of the literature show that the treatment with PCCs in patients on VKAs therapy is associated with a low risk of thromboembolic complications providing important information on the safety of this approach. Moreover, also the risk of viral transmission, although evaluated in few studies only, appears to be negligible. The findings of a low thromboembolic risk have been further confirmed by the results of the subgroup analyses separately evaluating treatment with 3 or 4-factors PCCs and different indications for PCCs therapy. Disclosures: Crowther: Pfizer: Consultancy; Leo Pharma: Research Funding; Boehringer Ingelheim: Research Funding.

Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists

2011 ◽  
Vol 106 (09) ◽  
pp. 429-438 ◽  
Author(s):  
Chiara Marchesi ◽  
Matteo Pierfranceschi ◽  
Mark Crowther ◽  
David Garcia ◽  
Elaine Hylek ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Total Mortality ◽  
Thromboembolic Complication ◽  
Thromboembolic Complications ◽  
Weighted Mean ◽  
Prothrombin Complex Concentrates ◽  
Anticoagulation Reversal

SummaryProthrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8–2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0–3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9–16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.

Effect of Vitamin K Intake on the Stability of Treatment with Vitamin K Antagonists: A Systematic Review of the Literature

2016 ◽  
Vol 42 (06) ◽  
pp. 671-681 ◽  
Author(s):  
Mark Crowther ◽  
Matteo Galli ◽  
Fulvio Pomero ◽  
David Garcia ◽  
Nathan Clark ◽  
...  
Keyword(s):  
Systematic Review ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Review Of The Literature ◽  
The Stability

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001678
Author(s):  
Nazariy Koval ◽  
Mariana Alves ◽  
Rui Plácido ◽  
Ana G Almeida ◽  
João Eurico Fonseca ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antiphospholipid Syndrome ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Prevention Of Thromboembolic Events

BackgroundDespite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.ObjectiveWe aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.MethodsAn electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.ResultsWe included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA—RR 1.69, 95% CI 1.09 to 2.62, I²—24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.ConclusionsCurrent evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.Trial registration numberCRD42020216178.

Prothrombin Complex Concentrates Compared with Frozen Plasma for Urgent Reversal of Vitamin K Antagonists: A Single Centre Retrospective Review

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4296-4296
Author(s):  
Lauren J. Lee ◽  
Jay Chi ◽  
Kate M. Chipperfield ◽  
Paul R. Yenson
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Categorical Variables ◽  
Thromboembolic Events ◽  
Prothrombin Complex Concentrates ◽  
Significant Difference ◽  
Bleeding Episodes ◽  
Chi Square Analysis ◽  
Frozen Plasma ◽  
Transfusion Reactions

Abstract Background: Vitamin K antagonists (VKAs) are associated with a risk of major bleeding requiring urgent reversal with frozen plasma (FP) or prothrombin complex concentrates (PCC) and concurrent vitamin K administration. Several treatment guidelines currently recommend PCC over FP for urgent reversal in VKA-associated bleeding. Four-factor PCC (Octaplex®, Beriplex®) has been available in Canada since 2008 with a change in national dosing recommendations in 2012. We conducted a retrospective study to determine the efficacy and safety of PCC in comparison with FP in patients presenting with bleeding and requiring VKA reversal. Methods: We retrospectively reviewed all consecutive bleeding episodes requiring VKA reversal at Vancouver General Hospital (VGH) for 2 cohorts of patients: i) those who received FP (July 28, 2008 to July 27, 2010); and ii) those who received PCC, during two time periods (July 28, 2008 to July 27, 2010; and September 1, 2011 to December 31, 2012) during which Canadian national dosing recommendations had changed. The PCC data however were pooled as no significant differences between the early and later PCC cohorts were found. Details of VKA reversal were reviewed, including patient demographics, bleeding type, indication for VKA therapy, dose of PCC or FP, admission hematologic parameters, INR value subsequent to completion of PCC or FP infusion, time to complete infusion, transfusion requirements, vitamin K dose and route of administration, transfusion reactions, thrombotic events (within 30 days) and mortality during hospitalization. The primary outcome was the proportion of patients achieving a target INR defined as ≤1.5 following the initial order of PCC or FP. Subject characteristics were compared using two-sided t-tests for continuous and Chi-square analysis for categorical variables. Predictors of mortality were analyzed with binary logistic regression. Results: A total of 201 bleeding episodes occurred in 191 patients. PCC was used in 89 episodes (44%). The most common indication for VKA was atrial fibrillation (81%). Mean PCC dose was 1489 U (range 500-3000 U). Mean FP dose was 3.1 U (range 1-10 U). Target INR was achieved in 86% of episodes in the PCC group versus 60% with FP (p<0.001). Mean time to complete the reversal agent was 4.4 hours with PCC versus 8.7 hours with FP (p<0.001). There was no significant difference in thromboembolic events between FP and PCC with 4 thromboembolic events occurring in each treatment group: 2 strokes, 1 myocardial infarction, and 1 recurrent deep vein thrombosis occurred in the PCC cohort. No transfusion-related reactions occurred in the PCC group compared with 12.6% with FP (p<0.001). Mortality was significantly higher in the PCC group (25% vs. 11%, p=0.010); however, intracranial bleeding (ICH) was more common in the PCC group (62% vs. 31%, p<0.001) and was the only independent predictor of mortality. Vitamin K was not administered in 20% of episodes, including 17% of episodes of ICH. Conclusion: PCC is effective in the urgent reversal of VKA with faster and more complete INR reversal, significantly fewer transfusion reactions and no increase in thromboembolic events in comparison to FP. Along with vitamin K, PCC should be the agent of choice for VKA reversal in bleeding patients. Disclosures Chipperfield: Boehringer Ingelheim: Honoraria. Yenson:Octapharma Canada: Unrestricted Education Grant Other; Alexion Pharmaceuticals: Honoraria.

scholarly journals Cardioversion Safety – Are We Doing Enough?

Cardiology ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 740-745
Author(s):  
Mohsen Khatami ◽  
Marita Knudsen Pope ◽  
Sophie Le Page ◽  
Petra Radic ◽  
Valentina Schirripa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Vitamin K ◽  
Prospective Studies ◽  
Time Window ◽  
Vitamin K Antagonists ◽  
Thromboembolic Events ◽  
Thromboembolic Complications ◽  
Increased Risk ◽  
Subgroup Analyses

There is a considerable periprocedural risk of thromboembolic events in atrial fibrillation patients undergoing cardioversion, and treatment with anticoagulants is therefore a hallmark of cardioversion safety. Based on retrospective subgroup analyses and prospective studies, non-vitamin K anticoagulants are at least as efficient as vitamin K-antagonists in preventing thromboembolic complications after cardioversion. The risk of thromboembolic complications after cardioversion very much depends on the comorbidities in a given patient, and especially heart failure, diabetes, and age &#x3e;75 years carry a markedly increased risk. Cardioversion has been considered safe within a 48-h time window after onset of atrial fibrillation without prior treatment with anticoagulants, but recent studies have set this practice into question based on e.g. erratic debut assessment of atrial fibrillation. Therefore, a simple and more practical approach is here suggested, where early cardioversion is performed only in hemodynamically unstable patients.

scholarly journals Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

2021 ◽  
Vol 10 (15) ◽  
pp. 3212
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Laura Piccioni ◽  
Carmelo Massimiliano Rao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Advance ◽  
Thromboembolic Events ◽  
Thromboembolic Risk ◽  
Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

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