scholarly journals Faculty Opinions recommendation of Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis.

2019 ◽  
Author(s):  
Charles Marc Samama
Keyword(s):  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor

scholarly journals Management of direct factor Xa inhibitor–related major bleeding with prothrombin complex concentrate: a meta-analysis

2019 ◽  
Vol 3 (2) ◽  
pp. 158-167 ◽  
Author(s):  
Siavash Piran ◽  
Rasha Khatib ◽  
Sam Schulman ◽  
Ammar Majeed ◽  
Anne Holbrook ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Meta Analysis ◽  
Case Series ◽  
Factor Xa ◽  
The United States ◽  
Effective Management ◽  
Direct Factor ◽  
All Cause Mortality ◽  
Fxa Inhibitor

Abstract A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor–related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor–related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor–related major bleeding.

Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients

2018 ◽  
Vol 35 (9) ◽  
pp. 903-908 ◽  
Author(s):  
Teresa A. Allison ◽  
Pei Jen Lin ◽  
Jennifer A. Gass ◽  
Kenneth Chong ◽  
Samuel J. Prater ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Prothrombin Complex Concentrate ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Final Analysis ◽  
Factor Xa Inhibitor ◽  
Direct Factor

Objective: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. Methods: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. Results: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. Conclusions: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.

Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Charlie J. Nederpelt ◽  
Leon Naar ◽  
Pieta Krijnen ◽  
Saskia le Cessie ◽  
Haytham M. A. Kaafarani ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Andexanet Alfa

Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents

2012 ◽  
Vol 107 (02) ◽  
pp. 253-259 ◽  
Author(s):  
Toshio Fukuda ◽  
Yuko Honda ◽  
Chikako Kamisato ◽  
Toshiro Shibano ◽  
Yoshiyuki Morishima
Keyword(s):  
Venous Thrombosis ◽  
Prothrombin Complex Concentrate ◽  
Bleeding Time ◽  
Factor Viia ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Thrombosis Model ◽  
Haemostatic Agents

SummaryEdoxaban, an oral, direct factor Xa inhibitor, has a similar or low incidence of bleeding events compared with other anticoagulants in clinical trials. Therefore, agents to reverse the anticoagulant effects of edoxaban could be desirable in emergency situations. In this study, the reversal effects of haemostatic agents were determined on prothrombin time (PT) prolongation in vitro and bleeding time prolongation in vivo by edoxaban. PT using human plasma was measured in the presence of edoxaban at therapeutic and excess concentrations with the haemostatic agents, prothrombin complex concentrate (PPSB-HT), activated prothrombin complex concentrate (Feiba), and recombinant factor VIIa (rFVIIa). In rats, rFVIIa and Feiba was given during intensive anticoagulation with edoxaban. The haemostatic effect was evaluated in a model of planta template bleeding and a potential prothrombotic effect was evaluated in a venous thrombosis model. PPSB-HT, Feiba, and rFVIIa concentration-dependently shortened PT prolonged by edoxaban. Among these, rFVIIa and Feiba showed potent activities in reversing the PT prolongation by edoxaban. rFVIIa (1 and 3 mg/kg, i.v.) and Feiba (100 U/kg, i.v.) significantly reversed edoxaban (1 mg/kg/h)-induced prolongation of bleeding time in rats. In a rat venous thrombosis model, no potentiation of thrombus formation was observed when the highest dose (3 mg/kg) of rFVIIa was added to edoxaban (0.3 and 1 mg/kg/h) compared with the control. The present study indicated that rFVIIa, Feiba, and PPSB-HT have the potential to be reversal agents for edoxaban.

Extended Thromboprophylaxis with Rivaroxaban Compared with Short-Term Thromboprophylaxis with Enoxaparin after Total Hip Arthroplasty: The RECORD2 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 307-307 ◽  
Author(s):  
Ajay K. Kakkar ◽  
Benjamin Brenner ◽  
Ola E. Dahl ◽  
Bengt I. Eriksson ◽  
Patrick Mouret ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Major Bleeding ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Direct Factor ◽  
Short Term ◽  
Double Blind

Abstract Venous thromboembolism (VTE) is a common, potentially fatal complication of major orthopaedic surgery. Pharmacologic thromboprophylaxis is recommended for patients undergoing total hip arthroplasty (THA) for a minimum of 10 days, and up to 35 days. However, extended thromboprophylaxis is not universally used. Therefore, this trial was conducted to evaluate the potential benefits of extended thromboprophylaxis after THA. RECORD2 is the largest, prospective, randomized clinical trial conducted to date, in this indication. This global, phase III, double-blind trial, was designed to compare short-term thromboprophylaxis with a low molecular weight heparin - enoxaparin - with extended thromboprophylaxis for up to 5 weeks with a novel, oral, direct Factor Xa inhibitor - rivaroxaban after THA. Patients received subcutaneous enoxaparin 40 mg once daily (od), beginning the evening before surgery, continuing for 10–14 days (short-term prophylaxis), and followed by placebo until day 35±4, or oral rivaroxaban 10 mg od beginning 6–8 hours after surgery and continuing for 35±4 days (extended prophylaxis). Mandatory, bilateral venography was conducted at the end of the extended treatment period. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The main secondary efficacy endpoint was major VTE; the composite of proximal DVT, non-fatal PE, and VTE-related death. Major and non-major bleeding during double-blind treatment were the primary and secondary safety endpoints, respectively. A total of 2509 patients were randomized; 2457 were included in the safety population and 1733 in the modified intention-to-treat (mITT) population. Extended thromboprophylaxis with rivaroxaban was associated with a significant reduction in the incidence of the primary efficacy endpoint and major VTE, compared with short-term thromboprophylaxis with enoxaparin (Table). The incidences of major and non-major bleeding were similar in both groups (Table). In conclusion, extended duration rivaroxaban was significantly more effective than short term enoxaparin for the prevention of VTE, including major VTE, in patients undergoing THA. Furthermore, this large trial demonstrated that extended thromboprophylaxis provides substantial benefits for patients undergoing THA, and that the oral, direct Factor Xa inhibitor rivaroxaban provides a safe and effective option for such a strategy. Short-term s.c. enoxaparin 40 mg od % (n/N) Extended oral rivaroxaban 10 mg od % (n/N) Relative risk reduction (%) P-value for difference DVT, non-fatal PE, and all-cause mortalitya 9.3% (81/869) 2.0% (17/864) 79% P<0.001 Major VTEb 5.1% (49/962) 0.6% (6/961) 88% P<0.001 Major bleedingc 0.1% (1/1229) 0.1% (1/1228) - P=0.980 Non-major bleedingc 5.5% (67/1229) 6.5% (80/1228) - P=0.246

scholarly journals Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1257
Author(s):  
Johanes Nugroho Eko Putranto ◽  
Ardyan Wardhana ◽  
Yoga Alfian Noor ◽  
Pirhot Lambok Marnala Yosua Siahaan ◽  
Makhyan Jibril Al Farabi
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Cochrane Library ◽  
Factor Xa Inhibitor ◽  
Patients With Cancer

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel–Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45–0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33–0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31–3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35–0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83–2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55–0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

Rivaroxaban - An Oral, Direct Factor Xa Inhibitor - for Thromboprophylaxis after Total Knee Arthoplasty: The RECORD3 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 308-308 ◽  
Author(s):  
Michael R. Lassen ◽  
Alexander G.G. Turpie ◽  
Nadia Rosencher ◽  
Lars C. Borris ◽  
Walter Ageno ◽  
...  
Keyword(s):  
Relative Risk ◽  
Risk Reduction ◽  
Major Bleeding ◽  
Relative Risk Reduction ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Intention To Treat ◽  
Total Knee ◽  
Treat Population

Abstract Introduction Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. In RECORD3, a phase III trial, the efficacy and safety of once-daily (od) rivaroxaban was compared with od enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA). MethodsIn this multicenter, double-blind, double-dummy trial, patients undergoing TKA were randomized to receive either oral rivaroxaban 10 mg od or subcutaneous enoxaparin 40 mg od. Enoxaparin was initiated 12 hours before surgery, and rivaroxaban 6–8 hours after surgery; both were continued for 10–14 days. The primary outcome was the composite of deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause mortality. Secondary efficacy outcomes included major VTE (the composite of proximal DVT, PE and VTE-related death) and symptomatic VTE. The main safety outcome was major bleeding, and secondary outcomes included non-major bleeding and adverse events. Results A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The primary efficacy outcome occurred in 9.6% of patients receiving rivaroxaban compared with 18.9% of those receiving enoxaparin (relative risk reduction 49%; p<0.001; Table). Rivaroxaban was also significantly more effective than enoxaparin at reducing major VTE, with a relative risk reduction of 62%. Symptomatic VTE was also lower with rivaroxaban than with enoxaparin. The incidences of major and non-major bleeding were similar in both the rivaroxaban and enoxaparin groups, as was the incidence of other adverse events. During the treatment period, there were no deaths or PEs in the rivaroxaban group, and two deaths and four PEs occurred in the enoxaparin group. Conclusions Rivaroxaban was superior to enoxaparin for the prevention of VTE after TKA in this study, with a similar, low rate of bleeding. This is the first study to demonstrate the safety and efficacy of a fixed, unmonitored regimen of an oral, direct Factor Xa inhibitor - rivaroxaban - for the prevention of VTE after major orthopaedic surgery. Rivaroxaban 10 mg od % (n/N) Enoxaparin 40 mg od % (n/N) Relative risk reduction (%) p -value for difference aModified intention-to-treat-population; bModified intention-to-treat population valid for major VTE analysis; cSafety population who underwent surgery; dSafety population; *Calculated for the absolute risk difference DVT, non-fatal PE, and all-cause mortalitya 9.6% (79/824) 18.9% (166/878) 49% p <0.001 Major VTEb 1.0% (9/908) 2.6% (24/925) 62% p =0.016 Symptomatic VTEc 0.7% (8/1201) 2.0% (24/1217) 66% p =0.005 Major bleedingd 0.6% (7/1220) 0.5% (6/1239) - p =0.774* Non-major bleedingd 4.3% (53/1220) 4.4% (54/1239) - p =0.990*

Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis after Total Hip Arthroplasty: The RECORD1 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 6-6 ◽  
Author(s):  
Bengt I. Eriksson ◽  
Lars C. Borris ◽  
Richard J. Friedman ◽  
Sylvia Haas ◽  
Menno V. Huisman ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Efficacy And Safety ◽  
Direct Factor ◽  
Mitt Population ◽  
All Cause Mortality ◽  
Subcutaneous Enoxaparin

Abstract Background Thromboprophylaxis for at least 10 days and for up to 4–5 weeks is recommended after total hip arthroplasty (THA). Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. RECORD1 was a phase III, multinational, randomized, double-blind, double-dummy trial, conducted to determine the efficacy and safety of oral rivaroxaban, compared with subcutaneous enoxaparin, for 5 weeks of thromboprophylaxis in patients undergoing THA. Methods Patients received rivaroxaban 10 mg beginning 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od, beginning the evening before surgery (restarting 6–8 hours after surgery). Therapy continued for 35±4 days and mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The primary efficacy analysis was a test for non-inferiority in the per-protocol (PP) population, followed by a test for superiority in the modified intention-to-treat (mITT) population. The main secondary efficacy endpoint was major venous thromboembolism (VTE): the composite of proximal DVT, non-fatal PE and VTE-related death. Major and non-major bleeding during the active treatment period were the primary and secondary safety endpoints, respectively. Results A total of 4541 patients were randomized; 4433 were eligible for the safety population, 3153 for the mITT population, and 3029 for the PP population. The criteria for non-inferiority were met and testing for superiority was performed. Rivaroxaban significantly reduced the incidence of the primary efficacy endpoint (p<0.001) and major VTE (p<0.001), compared with enoxaparin, in the mITT population (Table). The incidence of major and non-major bleeding events was similar in both groups (Table). Conclusions Rivaroxaban was significantly more effective than enoxaparin for extended prophylaxis after THA, with a similar safety profile. This is the first pivotal trial to demonstrate the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor - rivaroxaban - for extended thromboprophylaxis after THA. Rivaroxaban 10mg od % (n/N) Enoxaparin 40 mg od % (n/N) Relative risk reduction % (95% CI) P-value for difference DVT, non-fatal PE, and all-cause mortality 1.1% (18/1595) 3.7% (58/1558) 70% (49–82%) P<0.001 Major VTE 0.2% (4/1686) 2.0% (33/1678) 88% (66–96%) P<0.001 Major bleeding 0.3% (6/2209) 0.1% (2/2224) - P=0.178 Non-major bleeding 5.8% (128/2209) 5.8% (129/2224) - P=1.000

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