Multichamber intracardiac thrombosis during novel oral anticoagulation reversal with activated prothrombin complex concentrate infusion.
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ABSTRACT:
SUBMITTER: Mar PL
PROVIDER: S-EPMC7064797 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Multichamber intracardiac thrombosis during novel oral anticoagulation reversal with activated prothrombin complex concentrate infusion.
Mar Philip L PL Brown Lorrel E LE Chong Luke L Gopinathannair Rakesh R
HeartRhythm case reports 20191221 3
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Project description:Multiple agents exist for the reversal of oral Factor Xa inhibitor (FXa) associated bleeding, including Coagulation FXa Recombinant, Inactivated zhzo (andexanet alfa) and 4-factor prothrombin complex concentrate (4F-PCC). While classified as a 3F-PCC product, Profilnine contains up to 35 IU of Factor VII (per 100 IU of Factor IX) in addition to therapeutic levels of Factors II, IX, and X, and has demonstrated a similar impact on prothrombin time and blood product usage in non-warfarin related bleeding. This was a retrospective, multicenter study at four medical centers of adult patients who presented with major bleeding associated with oral FXa inhibitors and received either 4F-PCC (n = 64) or 3F-PCC (n = 61). The primary outcome was hemostatic effectiveness. Secondary outcomes included the incidence of thromboembolism, in-hospital mortality, and length of stay. The most common indication for reversal was intracranial bleeding. For the primary outcome, 84% of all patients were rated as effective with no difference noted between the groups (p = 0.81). No significant difference between groups was found in the multivariable analysis adjusting for baseline differences between groups including race, total body weight, type of bleeding, and the use of antiplatelet therapy. There was no difference in the length of stay, in-hospital mortality, or the incidence of thromboembolism between the groups. Overall, no significant differences were found in the effectiveness or safety of 4F-PCC and 3F-PCC use in the management of oral FXa inhibitor-associated bleeding. Further investigations are warranted to explore the use of 3F-PCC for this indication and its safety and effectiveness.
| S-EPMC11885330 | biostudies-literature
Project description:BackgroundSwift reversal of oral anticoagulation is deemed essential for the outcome of patients with anticoagulation-related critical bleeding. The aim of this systematic review was to evaluate the benefits and harms of prothrombin complex concentrate (PCC) in patients with oral anticoagulants-related critical bleeding.MethodsFor this systematic review CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Web of Science, and clinical trial registries were systematically searched. Clinical study reports were also requested from competent authorities. Eligible for inclusion were randomised clinical trials comparing PCC versus no intervention, placebo, or other reversal interventions in participants with critical bleeding related to ongoing treatment with vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC). Pre-specified primary outcomes were all-cause mortality, health-related quality of life, and serious adverse events for which meta-analyses, Trial Sequential Analysis, and GRADE assessments were conducted.ResultsThree trials, randomising a total of 291 participants, evaluated PCC against two different active comparators in participants with VKA-related critical bleeding, and two trials, randomising a total of 534 participants, evaluated PCC against two different active comparators in participants with factor Xa-related critical bleeding. Among participants with VKA-related critical bleeding, meta-analyses showed no evidence of a difference between PCC versus fresh frozen plasma (FFP) when assessing all-cause mortality (risk ratio [RR] 1.05; 95% confidence interval (CI) 0.27 to 4.05; low certainty), health-related quality of life (mean difference 1.04; 95% CI - 0.94 to 3.02; very low certainty), and serious adverse events (RR 1.33; 95% CI 0.94 to 1.88; very low certainty), but information is currently sparse. Among participants with factor Xa-related critical bleeding, PCC could not be shown superior or inferior to other reversal strategies (FFP or andexanet alfa) on any patient-relevant outcome, but information is currently sparse.ConclusionAmong participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life.
| S-EPMC11792222 | biostudies-literature
Project description:BackgroundThere is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events.MethodsA systematic review and meta-analysis was performed.ResultsTwenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%).ConclusionConsidering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events.Clinical trial registrationPROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.
| S-EPMC11225147 | biostudies-literature
Project description:Data on the use of activated prothrombin complex concentrate (aPCC) for the management of warfarin associated major bleeding is sparse. The objective of the study was to assess the achievement of effective clinical hemostasis using aPCC in patients presenting with major bleeding while on warfarin. We also assessed the safety of the drug. This retrospective study was conducted at a tertiary care teaching center in the USA where patients with major bleeding while receiving warfarin, and received aPCC were included. Efficacy of aPCC in achieving effective hemostasis was assessed according to the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria. Efficacy was also assessed by achieving INR < 1.5 after treatment. The primary safety endpoint was the occurrence of any thromboembolic complications. A total of 67 patients were included in the study. The most common site for bleeding was intracerebral hemorrhage (n = 37, 55.2%), followed by gastrointestinal bleed (n = 26, 38.8%). Clinical hemostasis was achieved in 46 (68.7%) patients and of the 21 (31.3%) patients who did not achieve clinical hemostasis, 16 died. Thirty nine (58.2%) patients achieved INR < 1.5. Five (7.5%) patients developed thromboembolic complications. This study suggests that the use of aPCCs is effective in achieving effective hemostasis in patients on warfarin presenting with major bleeding.
| S-EPMC8810750 | biostudies-literature
Project description:Background and purposeCurrent guidelines suggest that 3-factor prothrombin complex concentrate is a possible alternative to 4-factor products for the emergent reversal of bleeding secondary to warfarin. While multiple observational studies have evaluated various forms of 3-factor prothrombin complex concentrate individually, no study has compared the efficacy of the 2 products. The purpose of this study is to compare the efficacy and safety of Bebulin™ and Profilnine™ for the emergent reversal of warfarin-associated major bleeding.MethodsWe conducted a retrospective cohort study of patients receiving both Bebulin™ and Profilnine™ at an urban, academic medical center with comprehensive stroke center designation and a neurosurgical center of excellence. All patients were treated at a single center that utilized a fixed, weight-based dosing protocol. The primary outcome was the percentage of patients in each group achieving a goal international normalization ratio of 1.4 or less.ResultsThere was a significant difference in goal international normalization ratio achieved favoring Bebulin™ (85.5% vs 27.3%; P < .001) over Profilnine™. Median dose per kilogram of actual body weight was the same between the groups. When we assessed results by baseline™ international normalization ratio subgroup, more patients in the Bebulin™ group achieved goal when baseline values were 6 or less. No thrombotic events were documented in either group.ConclusionsWe found that patients treated with Bebulin™ experienced significantly higher rates of successful international normalization ratio reversal when compared to those who received Profilnine™. Further research is needed to determine the comparative efficacy between the 2 agents.
| S-EPMC7271618 | biostudies-literature
Project description:A multicenter, retrospective, observational study of 4-factor prothrombin complex concentrate (PCC) and/or fresh frozen plasma (FFP) use within routine clinical care unrelated to vitamin K antagonists was conducted. The PCC was administered preprocedure for correction of coagulopathy (prophylactic cohort) and treatment of bleeding postsurgery (treatment cohort). Of the 445 patients included, 40 were in the prophylactic cohort (PCC alone [n = 16], PCC and FFP [n = 5], FFP alone [n = 19]) and 405 were in the treatment cohort (PCC alone [n = 228], PCC and FFP [n = 123], FFP alone [n = 54]). Cardiovascular surgery was the most common setting. PCC doses ranged between 500 and 5000 IU. Effectiveness (assessed retrospectively) was reported as effective in 93.0% in the PCC-only group (95% confidence interval, 89.1% to 95.9%), 78.9% (70.8% to 85.6%) with PCC and FFP, and 86.3% (76.2% to 93.2%) with FFP alone. In the treatment cohort, international normalized ratio was significantly reduced in all 3 groups. In patients who received PCC, the rate of thromboembolic events (1.9%) was below rates in the literature for similar procedures. PCCs offer a potential alternative to FFP in the management of perioperative bleeding unrelated to oral anticoagulant therapy.
| S-EPMC6714747 | biostudies-literature
Project description:It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points.
| S-EPMC5351332 | biostudies-literature
Project description:Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The December 2013 monograph topics are vortioxetine, mechlorethamine gel, brimonidine tartrate topical gel, obinutuzumab, and miltefosine. The DUE/MUE is on vortioxetine.
| S-EPMC3875114 | biostudies-other
Project description:ImportanceIntracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear.ObjectiveTo compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management.Design, setting, and participantsIn this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023.Main outcomes and measuresThe primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified.ResultsA total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion.Conclusions and relevanceIn this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.
| S-EPMC10848059 | biostudies-literature
Project description: Not available
| S-EPMC6516823 | biostudies-literature