Browsing by Subject "Hemorrhage"

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    ItemOpen Access
    An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS).
    (Journal of thrombosis and thrombolysis, 2010-10) Dolor, Rowena J; Ruybalid, R Lynne; Uyeda, Lauren; Edson, Robert G; Phibbs, Ciaran; Vertrees, Julia E; Shih, Mei-Chiung; Jacobson, Alan K; Matchar, David B; THINRS Site Investigators
    Prior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.
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    ItemOpen Access
    Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial.
    (Circulation, 2022-03) Bahnson, Tristram D; Giczewska, Anna; Mark, Daniel B; Russo, Andrea M; Monahan, Kristi H; Al-Khalidi, Hussein R; Silverstein, Adam P; Poole, Jeanne E; Lee, Kerry L; Packer, Douglas L; CABANA Investigators

    Background

    Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

    Methods

    Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models.

    Results

    Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30-1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54-1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75-2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction P value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction P value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age.

    Conclusions

    We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias.

    Registration

    URL: https://www.

    Clinicaltrials

    gov; Unique identifier: NCT00911508.
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    ItemOpen Access
    Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation.
    (Journal of the American Heart Association, 2020-09) Hijazi, Ziad; Granger, Christopher B; Hohnloser, Stefan H; Westerbergh, Johan; Lindbäck, Johan; Alexander, John H; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Wallentin, Lars
    Background We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or cystatin C (CKD-EPICysC and CKD-EPICysC+Creatinine). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft-Gault (74.1 mL/min) and CKD-EPICysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft-Gault and CKD-EPICysC) to 0.99 (Modification of Diet in Renal Disease and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD-EPICysC) and 0.612 (CKD-EPICysC+Creatinine), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C-based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00412984.
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    Bleeding outcomes of inpatients receiving therapeutic plasma exchange: A propensity-matched analysis of the National Inpatient Sample.
    (Transfusion, 2022-02) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Onwuemene, Oluwatoyosi A

    Background

    Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE.

    Study design and methods

    In a cross-sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE-treated conditions. A 1:3 propensity-matched analysis of TPE- to non-TPE-treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes.

    Results

    The study population was 15,964 discharges, of which 3991 were TPE- treated. The prevalence of major bleeding was low (5.4%). When compared to non-TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16-1.63, p = .0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42-1.94, p < .0001), in-hospital mortality (OR = 1.45, 95% CI: 1.10-1.90, p = .0008), hospital length of stay (12.45 [95% CI: 11.95-12.97] vs. 7.38 [95% CI: 7.12-7.65] days, p < .0001) and total charges, ($125,123 [95% CI: $119,220-$131,317] vs. $61,953 [95% CI: $59,391-$64,625], p < .0001), and disposition to non-self-care (OR = 1.29, 95% CI: 1.19-1.39, p < .0001).

    Discussion

    The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE-associated bleeding.
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    ItemOpen Access
    Cardiovascular Outcomes After Lower Extremity Endovascular or Surgical Revascularization: The EUCLID Trial.
    (Journal of the American College of Cardiology, 2018-10) Baumgartner, Iris; Norgren, Lars; Fowkes, F Gerry R; Mulder, Hillary; Patel, Manesh R; Berger, Jeffrey S; Jones, W Schuyler; Rockhold, Frank W; Katona, Brian G; Mahaffey, Kenneth; Hiatt, William R; Executive Committee and Investigators of the EUCLID Trial
    BACKGROUND:Lower extremity revascularization (LER) is a common treatment in patients with peripheral artery disease (PAD), but long-term outcomes are poorly defined. OBJECTIVES:The aim was to analyze LER in the EUCLID (Examining Use of tiCagreLor In paD) trial to determine predictors and cardiovascular outcomes. METHODS:Patients were grouped according to whether they received a post-randomization LER (n = 1,738) or not (n = 12,147). All variables were assessed for significance in univariable and parsimonious multivariable models. The primary endpoint was myocardial infarction, ischemic stroke, or cardiovascular death; major adverse limb events (MALE) included acute limb ischemia or major amputation. RESULTS:A post-randomization LER occurred in 12.5% of patients and was an endovascular LER in 74.7%. Endovascular LERs were performed more often in North America, whereas surgical procedures occurred more frequently in Europe. Independent factors predicting LER were prior and type of prior LER, geographic region, limb symptoms, diabetes, and smoking. A post-randomization LER was associated with an increased risk for the primary endpoint (hazard ratio: 1.60; 95% confidence interval: 1.35 to 1.90; p < 0.0001) and MALE (hazard ratio: 12.0; 95% confidence interval: 9.47 to 15.30; p < 0.0001). Event rates for the primary endpoint after LER were numerically higher in the surgical subgroup, but MALE were similar between surgical and endovascular LER. CONCLUSIONS:In the EUCLID trial, LER was most often endovascular. Following LER, there was an increased hazard for the primary endpoint (with higher event rates in the surgical group) and a markedly increased risk for MALE events (with similar event rates between surgical and endovascular LER procedures). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).
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    ItemOpen Access
    Catastrophic antiphospholipid syndrome with concurrent thrombotic and hemorrhagic manifestations.
    (Lupus, 2013-07) Rangel, ML; Alghamdi, I; Contreras, G; Harrington, T; Thomas, DB; Barisoni, L; Andrews, D; Wolf, M; Asif, A; Nayer, A
    Antiphospholipid syndrome (APS) is a distinct autoimmune prothrombotic disorder due to pathogenic autoantibodies directed against proteins that bind to phospholipids. APS is characterized by arterial and venous thrombosis and their clinical sequelae. Catastrophic antiphospholipid syndrome (CAPS) is a rare and often fatal form of APS characterized by disseminated intravascular thrombosis and ischemic injury resulting in multiorgan failure. Rarely, intravascular thrombosis in CAPS is accompanied by hemorrhagic manifestations such as diffuse alveolar hemorrhage. Here, we report a 43-year-old woman who presented with anemia, acute gastroenteritis, abnormal liver function tests, bilateral pulmonary infiltrates, and a systemic inflammatory response syndrome. The patient developed respiratory failure as a result of diffuse alveolar hemorrhage followed by acute renal failure. Laboratory tests disclosed hematuria, proteinuria, and reduced platelet count. Microbiologic tests were negative. A renal biopsy demonstrated acute thrombotic microangiopathy and extensive interstitial hemorrhage. Serologic tests disclosed antinuclear antibodies and reduced serum complement C4 concentration. Coagulation studies revealed the lupus anticoagulant and autoantibodies against cardiolipin, beta 2-glycoprotein I, and prothrombin. High-dose glucocorticoids and plasma exchange resulted in rapid resolution of pulmonary, renal, and hematological manifestations. This rare case emphasizes that CAPS can present with concurrent thrombotic and hemorrhagic manifestations. Rapid diagnosis and treatment may result in complete recovery.
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    Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.
    (Vox sanguinis, 2021-02) Moreno-Duarte, Ingrid; Cooter, Mary; Onwuemene, Oluwatoyosi A; Ghadimi, Kamrouz; Welsby, Ian J

    Background and objectives

    Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB.

    Materials and methods

    We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017.

    Results

    Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related.

    Conclusion

    Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB.
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    Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation.
    (J Am Heart Assoc, 2013-11-25) Steinberg, Benjamin A; Holmes, Dajuanicia N; Piccini, Jonathan P; Ansell, Jack; Chang, Paul; Fonarow, Gregg C; Gersh, Bernard; Mahaffey, Kenneth W; Kowey, Peter R; Ezekowitz, Michael D; Singer, Daniel E; Thomas, Laine; Peterson, Eric D; Hylek, Elaine M; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators and Patients
    BACKGROUND: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. METHODS AND RESULTS: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow-up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). CONCLUSIONS: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. CLINICAL TRIAL REGISTRATION URL: Clinicaltrials.gov. Unique identifier: NCT01165710.
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    Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.
    (J Am Heart Assoc, 2014-04-14) Sherwood, Matthew W; Wiviott, Stephen D; Peng, S Andrew; Roe, Matthew T; Delemos, James; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.
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    Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
    (Heart (British Cardiac Society), 2019-02) Christersson, Christina; Wallentin, Lars; Andersson, Ulrika; Alexander, John H; Alings, Marco; De Caterina, Raffaele; Gersh, Bernard J; Granger, Christopher B; Halvorsen, Sigrun; Hanna, Michael; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; Oh, Byung-Hee; Siegbahn, Agneta

    Objectives

    Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).

    Methods

    The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.

    Results

    In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.

    Conclusions

    Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.

    Trial registration number

    NCT00412984.
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    Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.
    (JAMA, 2019-04) Packer, Douglas L; Mark, Daniel B; Robb, Richard A; Monahan, Kristi H; Bahnson, Tristram D; Poole, Jeanne E; Noseworthy, Peter A; Rosenberg, Yves D; Jeffries, Neal; Mitchell, L Brent; Flaker, Greg C; Pokushalov, Evgeny; Romanov, Alexander; Bunch, T Jared; Noelker, Georg; Ardashev, Andrey; Revishvili, Amiran; Wilber, David J; Cappato, Riccardo; Kuck, Karl-Heinz; Hindricks, Gerhard; Davies, D Wyn; Kowey, Peter R; Naccarelli, Gerald V; Reiffel, James A; Piccini, Jonathan P; Silverstein, Adam P; Al-Khalidi, Hussein R; Lee, Kerry L; CABANA Investigators

    Importance

    Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain.

    Objective

    To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF.

    Design, setting, and participants

    The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017.

    Interventions

    The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines.

    Main outcomes and measures

    The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence.

    Results

    Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001).

    Conclusions and relevance

    Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.

    Trial registration

    ClinicalTrials.gov Identifier: NCT00911508.
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    Effect of home testing of international normalized ratio on clinical events.
    (The New England journal of medicine, 2010-10) Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip; THINRS Executive Committee and Site Investigators

    Background

    Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.

    Methods

    We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).

    Results

    The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).

    Conclusions

    As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.).
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    Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children.
    (Transfusion, 2020-12) Nellis, Marianne E; Spinella, Philip C; Tucci, Marisa; Stanworth, Simon J; Steiner, Marie E; Cushing, Melissa M; Davis, Peter J; Karam, Oliver; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, Pediatric Critical Care Blood Research Network (BloodNet), and the P3T Investigators†
    The safety of platelet (PLT) concentrates with longer storage duration has been questioned due to biochemical and functional changes that occur during blood collection and storage. Some studies have suggested that transfusion efficacy is decreased and immune system dysfunction is worsened with increased storage age. We sought to describe the effect of PLT storage age on laboratory and clinical outcomes in critically ill children receiving PLT transfusions.

    Study design and methods

    We performed a secondary analysis of a prospective, observational point-prevalence study. Children (3 days to 16 years of age) from 82 pediatric intensive care units in 16 countries were enrolled if they received a PLT transfusion during one of the predefined screening weeks. Outcomes (including PLT count increments, organ dysfunction, and transfusion reactions) were evaluated by PLT storage age.

    Results

    Data from 497 patients were analyzed. The age of the PLT transfusions ranged from 1 to 7 days but the majority were 4 (24%) or 5 (36%) days of age. Nearly two-thirds of PLT concentrates were transfused to prevent bleeding. The indication for transfusion did not differ between storage age groups (P = .610). After patient and product variables were adjusted for, there was no association between storage age and incremental change in total PLT count or organ dysfunction scoring. A significant association between fresher storage age and febrile transfusion reactions (P = .002) was observed.

    Conclusion

    The results in a large, diverse cohort of critically ill children raise questions about the impact of storage age on transfusion and clinical outcomes which require further prospective evaluation.
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    Hemostatic effects of therapeutic plasma exchange: A concise review.
    (Journal of clinical apheresis, 2022-06) Soares Ferreira Júnior, Alexandre; Hodulik, Kimberly; Barton, Karen D; Onwuemene, Oluwatoyosi A
    Therapeutic plasma exchange (TPE) alters the hemostatic balance. Contributing to TPE's hemostatic effects is the mechanical processing of blood in the extracorporeal circuit, circuit anticoagulant, type of replacement fluid, TPE schedule and number of procedures, TPE timing relative to invasive procedures, and removal of nontargeted components such as platelets, coagulation proteins, and cytokines. Although TPE's hemostatic effects are well established, how it impacts the bleeding risk is not clearly understood. In this concise review, we describe the effects of the above TPE-related factors on hemostatic balance, present data on the effects of TPE on blood hemostasis, including its effects on platelet counts and clotting assays, and review the literature on the impact of TPE-induced hemostatic changes on TPE-associated bleeding events. Finally, we discuss risk factors associated with bleeding during TPE and review the literature on TPE-associated hemostatic effects in the pediatric population.
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    ItemOpen Access
    Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin.
    (Circulation. Cardiovascular quality and outcomes, 2013-09) Zalesak, Martin; Siu, Kimberly; Francis, Kevin; Yu, Chen; Alvrtsyan, Hasmik; Rao, Yajing; Walker, David; Sander, Stephen; Miyasato, Gavin; Matchar, David; Sanchez, Herman

    Background

    Oral anticoagulation therapy is the primary tool in reducing stroke risk in patients with nonvalvular atrial fibrillation but is underused. Patients nonpersistent with therapy contribute to this underuse. The objective of this study was to compare persistence rates in newly diagnosed nonvalvular atrial fibrillation patients treated with warfarin versus dabigatran as their oral anticoagulation.

    Methods and results

    US Department of Defense administrative claims were used to identify patients receiving warfarin or dabigatran between October 28, 2010, and June 30, 2012. Patient records were examined for a minimum of 12 months before index date to restrict the analyses to those newly diagnosed with nonvalvular atrial fibrillation and naive-to-treatment, identifying 1775 on warfarin and 3370 on dabigatran. Propensity score matching was used to identify 1745 matched pairs. Persistence was defined as time on therapy to discontinuation. Kaplan-Meier curves were used to depict persistence over time. Cox proportional hazards model was used to determine the factors significantly associated with persistence. Using a 60-day permissible medication gap, the persistence rates were higher for dabigatran than for warfarin at both 6 months (72% versus 53%) and 1 year (63% versus 39%). Patients on dabigatran with a low-to-moderate risk of stroke (CHADS2<2) or with a higher bleed risk (HEMORR2HAGES>3) had a higher likelihood of nonpersistence (hazard ratios, 1.37; 95% confidence interval, 1.17-1.60; P<0.001; and hazard ratios, 1.24; 95% confidence interval, 1.04-1.47; P=0.016).

    Conclusions

    Patients who initiated dabigatran treatment were more persistent than patients who began warfarin treatment. Within each cohort, patients with lower stroke risk were more likely to discontinue therapy.
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    Intra-operative hydroxyethyl starch is not associated with post-craniotomy hemorrhage.
    (Springerplus, 2015) Feix, James A; Peery, C Andrew; Gan, Tong J; Warner, David S; James, Michael L; Zomorodi, Ali; McDonagh, David L
    BACKGROUND: Intraoperative intravascular volume expansion with hydroxyethyl starch-based colloids is thought to be associated with an increased risk of post-craniotomy hemorrhage. Evidence for this association is limited. Associations between resuscitation with hydroxyethyl starch and risk of repeat craniotomy for hematoma evacuation were examined. METHODS: Using a retrospective cohort of neurosurgical patients at Duke University Medical Center between March 2005 and March 2012, patient characteristics were compared between those who developed post-craniotomy hemorrhage and those who did not. RESULTS: A total of 4,109 craniotomy procedures were analyzed with 61 patients having repeat craniotomy for post-operative hemorrhage (1.5%). The rate of reoperation in the group receiving 6% High Molecular Weight Hydroxyethyl Starch (Hextend(®)) was 2.6 vs. 1.3% for patients that did not receive hetastarch (P = 0.13). The reoperation rate for those receiving 6% hydroxyethyl Starch 130/0.4 (Voluven(®)) was 1.4 vs. 1.6% in patients not receiving Voluven (P = 0.85). CONCLUSIONS: In this retrospective cohort, intra-operative hydroxyethyl starch was not associated with an increased risk of post-craniotomy hemorrhage.
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    Learning from 2523 trauma deaths in India- opportunities to prevent in-hospital deaths.
    (BMC health services research, 2017-02-16) Roy, Nobhojit; Kizhakke Veetil, Deepa; Khajanchi, Monty Uttam; Kumar, Vineet; Solomon, Harris; Kamble, Jyoti; Basak, Debojit; Tomson, Göran; von Schreeb, Johan
    A systematic analysis of trauma deaths is a step towards trauma quality improvement in Indian hospitals. This study estimates the magnitude of preventable trauma deaths in five Indian hospitals, and uses a peer-review process to identify opportunities for improvement (OFI) in trauma care delivery.All trauma deaths that occurred within 30 days of hospitalization in five urban university hospitals in India were retrospectively abstracted for demography, mechanism of injury, transfer status, injury description by clinical, investigation and operative findings. Using mixed methods, they were quantitatively stratified by the standardized Injury Severity Score (ISS) into mild (1-8), moderate (9-15), severe (16-25), profound (26-75) ISS categories, and by time to death within 24 h, 7, or 30 days. Using peer-review and Delphi methods, we defined optimal trauma care within the Indian context and evaluated each death for preventability, using the following categories: Preventable (P), Potentially preventable (PP), Non-preventable (NP) and Non-preventable but care could have been improved (NPI).During the 18 month study period, there were 11,671 trauma admissions and 2523 deaths within 30 days (21.6%). The overall proportion of preventable deaths was 58%, among 2057 eligible deaths. In patients with a mild ISS score, 71% of deaths were preventable. In the moderate category, 56% were preventable, and 60% in the severe group and 44% in the profound group were preventable. Traumatic brain injury and burns accounted for the majority of non-preventable deaths. The important areas for improvement in the preventable deaths subset, inadequacies in airway management (14.3%) and resuscitation with hemorrhage control (16.3%). System-related issues included lack of protocols, lack of adherence to protocols, pre-hospital delays and delays in imaging.Fifty-eight percent of all trauma deaths were classified as preventable. Two-thirds of the deaths with injury severity scores of less than 16 were preventable. This large subgroup of Indian urban trauma patients could possibly be saved by urgent attention and corrective action. Low-cost interventions such as airway management, fluid resuscitation, hemorrhage control and surgical decision-making protocols, were identified as OFI. Establishment of clinical protocols and timely processes of trauma care delivery are the next steps towards improving care.
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    Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.
    (Anesthesiology, 2023-05) Erdoes, Gabor; Faraoni, David; Koster, Andreas; Steiner, Marie E; Ghadimi, Kamrouz; Levy, Jerrold H
    Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.
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    Perioperative management of the bleeding patient.
    (British journal of anaesthesia, 2016-12) Ghadimi, K; Levy, JH; Welsby, IJ
    Perioperative bleeding remains a major complication during and after surgery, resulting in increased morbidity and mortality. The principal causes of non-vascular sources of haemostatic perioperative bleeding are a preexisting undetected bleeding disorder, the nature of the operation itself, or acquired coagulation abnormalities secondary to haemorrhage, haemodilution, or haemostatic factor consumption. In the bleeding patient, standard therapeutic approaches include allogeneic blood product administration, concomitant pharmacologic agents, and increasing application of purified and recombinant haemostatic factors. Multiple haemostatic changes occur perioperatively after trauma and complex surgical procedures including cardiac surgery and liver transplantation. Novel strategies for both prophylaxis and therapy of perioperative bleeding include tranexamic acid, desmopressin, fibrinogen and prothrombin complex concentrates. Point-of-care patient testing using thromboelastography, rotational thromboelastometry, and platelet function assays has allowed for more detailed assessment of specific targeted therapy for haemostasis. Strategic multimodal management is needed to improve management, reduce allogeneic blood product administration, and minimize associated risks related to transfusion.
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    Regional differences in outcomes with ablation versus drug therapy for atrial fibrillation: Results from the CABANA trial.
    (American heart journal, 2024-04) Cappato, Riccardo; Mark, Daniel B; Silverstein, Adam P; Noseworthy, Peter A; Bonitta, Gianluca; Poole, Jeanne E; Piccini, Jonathan P; Bahnson, Tristram D; Daniels, Melanie R; Al-Khalidi, Hussein R; Lee, Kerry L; Packer, Douglas L; CABANA Investigators

    Background

    The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes.

    Methods

    The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints.

    Results

    At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction P = .154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction P = .044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction P = .322).

    Conclusions

    In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics.

    Clinical trial registration

    ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508.