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1.
J Thromb Haemost ; 21(1): 76-82, 2023 01.
Article in English | MEDLINE | ID: mdl-36695399

ABSTRACT

BACKGROUND: Central venous catheters are prone to clotting, particularly in patients with cancer. Although low-molecular-weight heparin and direct oral anticoagulants, such as apixaban and rivaroxaban, have been evaluated for the prevention of catheter thrombosis, their efficacy remains uncertain. OBJECTIVES: Compare apixaban and rivaroxaban with enoxaparin for the prevention of catheter-induced clotting in vitro. METHODS: To address this uncertainty, we used a well-established microplate-based assay to compare the effects of enoxaparin, apixaban, and rivaroxaban on catheter-induced thrombosis and thrombin generation in human plasma. RESULTS: Consistent with our previous findings, catheter segments shortened the clotting time and promoted thrombin generation. When compared at concentrations with similar anti-factor Xa activity as enoxaparin, apixaban and rivaroxaban were >20-fold less potent than enoxaparin for the prevention of catheter-induced clotting and thrombin generation. CONCLUSION: The prevention of catheter thrombosis in patients with cancer is challenging. Clinical trials are needed to compare the efficacy of low-molecular-weight heparin with that of direct oral anticoagulants both for the prevention and treatment of catheter thrombosis.


Subject(s)
Neoplasms , Thrombosis , Humans , Enoxaparin/pharmacology , Enoxaparin/therapeutic use , Rivaroxaban/therapeutic use , Anticoagulants/therapeutic use , Thrombin , Pyridones/pharmacology , Pyridones/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Thrombosis/etiology , Thrombosis/prevention & control , Catheters , Neoplasms/drug therapy , Factor Xa Inhibitors/therapeutic use
2.
Thromb Haemost ; 123(1): 6-15, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36513278

ABSTRACT

IMPORTANCE: Aortic stenosis is the most common valvular disease, and more than 90% of patients who undergo aortic valve replacement receive a bioprosthetic valve. Yet optimal antithrombotic therapy after bioprosthetic aortic valve replacement remains uncertain, and guidelines provide contradictory recommendations. OBSERVATIONS: Randomized studies of antithrombotic therapy after bioprosthetic aortic valve replacement are small and underpowered. Observational data present opposing, and likely confounded, results. Historically, changes to guidelines have not been informed by high-quality new data. Current guidelines from different professional bodies provide contradictory recommendations despite citing the same evidence. CONCLUSION: Insufficient antithrombotic therapy after bioprosthetic aortic valve replacement has serious implications: ischemic stroke, systemic arterial thromboembolism, and clinical and subclinical valve thromboses. Unnecessarily intense antithrombotic therapy, however, increases risk of bleeding and associated morbidity and mortality. Professional bodies have used the current low-quality evidence and generated incongruent recommendations. Researchers should prioritize generating high-quality, randomized evidence evaluating the risks and benefits of antiplatelet versus anticoagulant therapy after bioprosthetic aortic valve replacement.


Subject(s)
Fibrinolytic Agents , Heart Valve Prosthesis Implantation , Humans , Anticoagulants/adverse effects , Aortic Valve/surgery , Fibrinolytic Agents/adverse effects , Heart Valve Prosthesis , Treatment Outcome , Randomized Controlled Trials as Topic
3.
JACC Cardiovasc Interv ; 15(6): 603-613, 2022 03 28.
Article in English | MEDLINE | ID: mdl-35331452

ABSTRACT

OBJECTIVES: The authors aimed to identify risk factors and outcomes associated with new-onset atrial fibrillation (NOAF) after transcatheter aortic valve replacement (TAVR). BACKGROUND: NOAF is a common complication after TAVR, although estimates of the precise occurrence are variable. This study sought to quantify the occurrence of NOAF after TAVR and to explore the outcomes and predictors associated with this complication. METHODS: We searched Medline, EMBASE, and the Cochrane database from 2016 to 2020 for articles that reported NOAF after TAVR. We extracted data for studies published before 2016 from a previous systematic review. We pooled data using a random effects model. RESULTS: We identified 179 studies with 241,712 total participants (55,271 participants with pre-existing atrial fibrillation (AF) were excluded) that reported NOAF from 2008 to 2020. The pooled occurrence of NOAF after TAVR was 9.9% (95% CI: 8.1%-12%). NOAF after TAVR was associated with a longer index hospitalization (mean difference = 2.66 days; 95% CI: 1.05-4.27), a higher risk of stroke in the first 30 days (risk ratio [RR]: 2.35; 95% CI: 2.12-2.61), 30-day mortality (RR: 1.76; 95% CI: 1.12-2.76), major or life-threatening bleeding (RR: 1.60; 95% CI: 1.39-1.84), and permanent pacemaker implantation (RR: 1.12; 95% CI: 1.05-1.18). Risk factors for the development of NOAF after TAVR included higher Society of Thoracic Surgeons score, transapical access, pulmonary hypertension, chronic kidney disease, peripheral vascular disease, and severe mitral regurgitation, suggesting that the risk for NOAF is highest in more comorbid TAVR patients. CONCLUSIONS: NOAF is common after TAVR. Whether AF after TAVR is a causal factor or a marker of sicker patients remains unclear.


Subject(s)
Aortic Valve Stenosis , Atrial Fibrillation , Transcatheter Aortic Valve Replacement , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Humans , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
4.
Ann Thorac Surg ; 110(2): 582-590, 2020 08.
Article in English | MEDLINE | ID: mdl-31877292

ABSTRACT

BACKGROUND: Patients with mechanical heart valves (MHVs) require warfarin to prevent thromboembolism. Dabigatran was less effective than warfarin in patients with MHVs, which prompted a black box warning against the use of direct oral anticoagulants for this indication. However, rivaroxaban and apixaban, which inhibit factor Xa, have not been evaluated in patients with MHVs. To determine whether rivaroxaban and apixaban would be effective, we used MHV-induced thrombin generation assays to compare them with warfarin either alone or in combination with dabigatran. METHODS: Thrombin generation in the absence or presence of MHV leaflets or sewing ring segments (SRSs) was quantified. Studies were done in control plasma; plasma from patients on warfarin; plasma containing varying concentrations of rivaroxaban, apixaban, or dabigatran alone; or plasma containing rivaroxaban plus dabigatran. RESULTS: Mean endogenous thrombin potential (ETP) increased 1.2-fold, 1.5-fold, and 1.8-fold in the presence of leaflets, Teflon (Terumo Aortic (Sunrise, FL)) SRSs, or Dacron (Terumo Aortic (Sunrise, FL)) SRSs, respectively. Rivaroxaban and apixaban reduced ETP at concentrations above 50 ng/mL but were less effective than warfarin. When rivaroxaban and dabigatran were combined, they suppressed ETP in a more than additive manner. CONCLUSIONS: Whereas warfarin suppresses MHV-induced thrombin generation, MHVs induce the generation of factor Xa in concentrations that overwhelm clinically relevant concentrations of rivaroxaban or apixaban. When used in combination, rivaroxaban and dabigatran are more effective than either agent is alone, suggesting that concomitant inhibition of factor Xa and thrombin is better than inhibition of either clotting enzyme alone.


Subject(s)
Dabigatran/therapeutic use , Heart Diseases/prevention & control , Heart Valve Prosthesis/adverse effects , Rivaroxaban/therapeutic use , Thrombin/antagonists & inhibitors , Thrombosis/prevention & control , Antithrombins/therapeutic use , Factor Xa Inhibitors/therapeutic use , Heart Diseases/etiology , Humans , Thrombin/metabolism , Thrombosis/blood , Thrombosis/etiology
5.
Circulation ; 140(23): 1933-1942, 2019 12 03.
Article in English | MEDLINE | ID: mdl-31790297

ABSTRACT

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.


Subject(s)
Anticoagulants/history , Heart Valve Prosthesis Implantation/history , Postoperative Complications/prevention & control , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Atrial Fibrillation/etiology , Drug Monitoring , Health Services Needs and Demand , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis/history , Hemorrhage/chemically induced , Hemorrhage/prevention & control , History, 20th Century , History, 21st Century , Humans , Multicenter Studies as Topic , Postoperative Complications/chemically induced , Postoperative Complications/etiology , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Thrombophilia/chemically induced , Vitamin K/antagonists & inhibitors
6.
Acta Biomater ; 94: 2-10, 2019 08.
Article in English | MEDLINE | ID: mdl-31226480

ABSTRACT

Blood-contacting medical devices are an integral part of modern medicine. Such devices may be used for only a few hours or may be implanted for life. Despite advances in biomaterial science, clotting on medical devices remains a common problem. Systemic administration of antiplatelet drugs or anticoagulants is often needed to reduce the risk of clotting. Although effective, such therapy increases the risk of bleeding, which can be fatal. This chapter (a) describes some of the commonly used blood-contacting devices and their potential complications, (b) provides an overview of the mechanisms that drive device-associated clotting, and (c) reviews the strategies employed to attenuate clotting on blood-contacting medical devices. STATEMENT OF SIGNIFICANCE: This paper is part 1 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.


Subject(s)
Anticoagulants/pharmacology , Biocompatible Materials , Blood Coagulation/drug effects , Equipment Design , Equipment and Supplies , Platelet Aggregation Inhibitors/pharmacology , Thrombin/chemistry , Adsorption , Animals , Cell Adhesion , Heart Valve Prosthesis , Humans , Materials Testing , Prostheses and Implants , Prosthesis Design , Stents , Surface Properties
7.
Ann Thorac Surg ; 107(5): 1581-1582, 2019 05.
Article in English | MEDLINE | ID: mdl-30641067
8.
Thromb Haemost ; 119(2): 328-339, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30616247

ABSTRACT

BACKGROUND: The optimal antithrombotic therapy after surgical bioprosthetic aortic valve replacement (BAVR) is uncertain. We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing antiplatelet therapy and anticoagulation in patients with surgical BAVR. METHODS: We searched Cochrane CENTRAL, MEDLINE and EMBASE from inception to 3 November 2017 for studies evaluating antiplatelet therapy versus anticoagulation early after surgical BAVR. We performed title and abstract screening, full-text review, risk of bias evaluation and data collection independently and in duplicate. We evaluated overall quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, and pooled data using a random effects model. RESULTS: We identified 2 RCTs (n = 397) and 5 observational studies (n = 2,012) meeting our eligibility criteria. The mean follow-up for all outcomes was 3 months in RCTs, and 10 months for observational studies. Antiplatelet compared with anticoagulant therapy demonstrated a trend towards fewer major bleeds in RCTs (relative risk [RR], 0.34; 95% confidence interval [CI], 0.11-1.04, p = 0.06, I 2 = 0%, low quality evidence), and significantly fewer major bleeds in observational studies (RR, 0.34; 95% CI, 0.20-0.58, p ≤ 0.0001, I 2 = 0%, very low quality evidence), but stroke, thromboembolism and mortality did not show a significant difference in either RCTs or observational studies. CONCLUSION: Antiplatelet therapy demonstrated reduced bleeding risk with no negative effects on stroke, thromboembolism or mortality compared with anticoagulation therapy after surgical BAVR. Our confidence in the results is reduced by the low quality of the available evidence.


Subject(s)
Anticoagulants/therapeutic use , Aortic Valve/surgery , Bioprosthesis , Heart Valve Diseases/surgery , Platelet Aggregation Inhibitors/therapeutic use , Blood Coagulation , Follow-Up Studies , Heart Valve Prosthesis , Hemorrhage/drug therapy , Humans , Observational Studies as Topic , Randomized Controlled Trials as Topic , Risk , Thromboembolism/prevention & control
9.
Thromb Haemost ; 118(5): 906-913, 2018 05.
Article in English | MEDLINE | ID: mdl-29614524

ABSTRACT

BACKGROUND: Guidelines recommend higher international normalized ratio (INR) targets for patients with mechanical valves believed to be at higher risk for thromboembolism. Higher INR targets are associated with increased bleeding risk. We performed a systematic review and meta-analysis assessing effects of lower and higher INR targets on thromboembolic and bleeding risk in patients with mechanical heart valves. METHODS: We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized controlled trials (RCTs) evaluating lower versus higher INR targets for adults with bileaflet mechanical valves. We performed title and abstract screening, full-text review, risk of bias evaluation and data collection independently and in duplicate. We pooled data using a random effects model and used the Grading of Recommendations Assessment, Development and Evaluation framework to evaluate overall quality of evidence. RESULTS: We identified six RCTs (n = 5,497). Lower INR targets were associated with significantly less bleeding-22% versus 40% (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.31, 0.93, p = 0.03, very low quality). There was no difference in thromboembolism-2% in both groups (RR: 1.28, 95% CI: 0.88, 1.85, p = 0.20, very low quality) or mortality-5.5% with lower INR targets versus 8.5% (RR: 1.00, 95% CI: 0.82, 1.21, p = 0.47, moderate quality). CONCLUSION: In patients with mechanical valves, higher INR targets are not supported by current evidence, which is of very low quality. In fact, our systematic review suggests that lower INR targets offer significantly lower bleeding risks with no significant difference in thromboembolic risk.


Subject(s)
Blood Coagulation/drug effects , Drug Monitoring/methods , Fibrinolytic Agents/therapeutic use , Heart Valve Prosthesis Implantation/adverse effects , Heart Valves/surgery , International Normalized Ratio , Thromboembolism/prevention & control , Evidence-Based Medicine , Fibrinolytic Agents/adverse effects , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation/instrumentation , Hemorrhage/chemically induced , Humans , Predictive Value of Tests , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/etiology , Treatment Outcome
10.
Europace ; 20(9): 1442-1450, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29186407

ABSTRACT

Aims: The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. Methods and results: We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Conclusion: Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.


Subject(s)
Atrial Fibrillation/surgery , Cardiac Surgical Procedures/methods , Catheter Ablation/methods , Cryosurgery/methods , Microwaves/therapeutic use , Atrial Fibrillation/complications , Humans , Mortality , Pacemaker, Artificial , Prosthesis Implantation/statistics & numerical data , Radiofrequency Ablation/methods , Randomized Controlled Trials as Topic , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Treatment Outcome
11.
Sci Rep ; 7(1): 11639, 2017 09 14.
Article in English | MEDLINE | ID: mdl-28912558

ABSTRACT

ABSTARCT: Catheter associated thrombosis is an ongoing problem. Omniphobic coatings based on tethering biocompatible liquid lubricants on self-assembled monolayers of hydrophobic organosilanes attenuate clotting on surfaces. Herein we report an efficient, non-invasive and robust process for coating catheters with an antithrombotic, omniphobic lubricant-infused coating produced using chemical vapor deposition (CVD) of hydrophobic fluorine-based organosilanes. Compared with uncoated catheters, CVD coated catheters significantly attenuated thrombosis via the contact pathway of coagulation. When compared with the commonly used technique of liquid phase deposition (LPD) of fluorine-based organosilanes, the CVD method was more efficient and reproducible, resulted in less disruption of the outer polymeric layer of the catheters and produced greater antithrombotic activity. Therefore, omniphobic coating of catheters using the CVD method is a simple, straightforward and non-invasive procedure. This method has the potential to not only prevent catheter thrombosis, but also to prevent thrombosis on other blood-contacting medical devices.


Subject(s)
Blood Coagulation/drug effects , Catheters , Coated Materials, Biocompatible/chemistry , Lubricants/chemistry , Silanes/chemistry , Silanes/pharmacology , Halogenation , Humans , Hydrophobic and Hydrophilic Interactions , Photoelectron Spectroscopy , Plasma Gases , Surface Properties
12.
F1000Res ; 6: 985, 2017.
Article in English | MEDLINE | ID: mdl-28713563

ABSTRACT

The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.

13.
BMJ Open ; 6(11): e013273, 2016 11 02.
Article in English | MEDLINE | ID: mdl-27807090

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) affects 10% of patients undergoing cardiac surgery and is an independent risk factor for all-cause mortality, ischaemic stroke and heart failure. Surgical AF ablation has been shown to significantly improve maintenance of sinus rhythm, however, small to medium size trials conducted to date lack the power required to assess patient-important outcomes such as mortality, stroke, heart failure and health-related quality of life. Moreover, a recent randomised trial (RCT) suggested harm by surgical AF ablation with an almost threefold increase in the requirement for permanent pacemaker postablation. We aim to perform a systematic review and meta-analysis to evaluate efficacy and safety of surgical AF ablation compared to no surgical ablation. METHODS AND ANALYSIS: We will search Cochrane CENTRAL, MEDLINE and EMBASE for RCTs evaluating the use of surgical AF ablation, including any lesion set, versus no surgical AF ablation in adults with AF undergoing any type of cardiac surgery. Outcomes of interest include mortality, embolic events, quality of life, rehospitalisation, freedom from AF and adverse events, including need for pacemaker and worsening heart failure. Independently and in duplicate, reviewers will screen references, assess eligibility of potentially relevant studies using predefined eligibility criteria and collect data using prepiloted forms. We will pool data using a random effects model and present results as relative risk with 95% CIs for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. We will assess risk of bias using the Cochrane Collaboration tool, and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Our results will help guide clinical practice by providing the most comprehensive analysis of risks and benefits associated with the procedure. Our results will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: CRD42015025988.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Quality of Life , Humans , Randomized Controlled Trials as Topic , Research Design , Stroke/etiology , Systematic Reviews as Topic
14.
Pol Arch Med Wewn ; 126(9): 688-696, 2016 Sep 05.
Article in English | MEDLINE | ID: mdl-27592622

ABSTRACT

Direct oral anticoagulants (DOACs) are rapidly replacing vitamin K antagonists (VKAs) for treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. When compared with conventional VTE treatment consisting of a parenteral anticoagulant followed by a VKA, the DOACs were equally effective for prevention of recurrence, but were associated with less bleeding. With similar efficacy, better safety, and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. Nonetheless, measures are needed to optimize the safety of DOACs. Focusing on these measures, this paper summarizes the results of phase III trials evaluating DOACs for VTE treatment; identifies which VTE patients are or are not candidates for DOACs; provides guidance on how to choose among DOACs; lists the licensed dosing information for DOACs; discusses the optimal treatment duration for VTE; describes periprocedural management of DOACs in patients requiring surgery or intervention; and finally, reviews the management of bleeding, including the role for specific reversal agents.


Subject(s)
Anticoagulants/adverse effects , Venous Thromboembolism/drug therapy , Administration, Oral , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Clinical Trials, Phase III as Topic , Coagulants/pharmacology , Dabigatran/administration & dosage , Dabigatran/antagonists & inhibitors , Dabigatran/therapeutic use , Humans , Patient Safety , Pyrazoles/administration & dosage , Pyrazoles/antagonists & inhibitors , Pyrazoles/therapeutic use , Pyridines/administration & dosage , Pyridines/antagonists & inhibitors , Pyridines/therapeutic use , Pyridones/administration & dosage , Pyridones/antagonists & inhibitors , Pyridones/therapeutic use , Rivaroxaban/administration & dosage , Rivaroxaban/antagonists & inhibitors , Rivaroxaban/therapeutic use , Thiazoles/administration & dosage , Thiazoles/antagonists & inhibitors , Thiazoles/therapeutic use
15.
Heart Asia ; 8(1): 62-4, 2016.
Article in English | MEDLINE | ID: mdl-27326236

ABSTRACT

The choice of prosthesis type in patients with valvular heart disease should always be individualised. The treating heart team must weigh the concerns surrounding durability of bioprosthetic valves compared with mechanical valves and the need for lifelong anticoagulation required with mechanical valves. In general, guidelines recommend that patients under the age of 60 would benefit from a mechanical valve, and those over 70 would benefit from a bioprosthetic valve. We would argue, in this context, that the most appropriate choice for this patient would be undertaking a mitral valve replacement with a mechanical prosthesis. This recommendation is based on two considerations: first, there is a high likelihood of failure of a bioprosthesis within an unacceptably short period of time, which would then necessitate a higher risk reoperation. Second, there is high likelihood of needing long-term anticoagulation in a patient with severe mitral stenosis due to the development of atrial fibrillation. While we do acknowledge the difficulty in managing long-term anticoagulation of patients in rural settings, there have nonetheless been significant advancements in this realm with the use of pharmacist-led thrombosis clinics and point of care international normalised ratio (INR) devices in the treatment of rural patients in low-income and middle-income countries. For these reasons, therefore, we would strongly advocate for a mechanical valve in this 44-year-old patient from a rural setting.

17.
Infect Control Hosp Epidemiol ; 37(5): 600-2, 2016 May.
Article in English | MEDLINE | ID: mdl-26782707

ABSTRACT

Based on a cohort of 966 patients, routine surveillance data were not sufficiently accurate for use in clinical trials investigating surgical site infections. Surveillance data can only be used if adequate 90-day follow-up is provided and if cases identified by surveillance are independently reviewed by a blinded outcome adjudication committee.


Subject(s)
Outcome and Process Assessment, Health Care/methods , Surgical Wound Infection/epidemiology , Thoracic Surgical Procedures/adverse effects , Canada , Humans , Sensitivity and Specificity
19.
J Am Heart Assoc ; 4(8): e002322, 2015 Aug 24.
Article in English | MEDLINE | ID: mdl-26304938

ABSTRACT

BACKGROUND: Patients with mechanical heart valves (MHV) require warfarin to prevent thromboembolism. Although dabigatran was as effective as warfarin for stroke prevention in atrial fibrillation when compared with warfarin in patients with MHV, the study was stopped early because of more strokes and bleeding with dabigatran. To determine why dabigatran was less effective than warfarin, we compared their effects on thrombin generation induced by MHV. METHODS AND RESULTS: Thrombin generation in the absence or presence of valve leaflets or sewing ring segments (SRS) was quantified. Studies were done in control plasma, plasma depleted of factors (F) XII, XI, or VII, plasma containing varying concentrations of dabigatran, or plasma from patients on dabigatran or warfarin with varying dabigatran concentrations or international normalized ratio (INR) values. Mean endogenous thrombin potential (ETP) increased 1.2-, 1.5-, and 1.8-fold in the presence of leaflets, Teflon SRS, and Dacron SRS, respectively. Whereas ETP in FVII-depleted and control plasma was similar, ETP was reduced to background levels in FXII-depleted plasma and abrogated in FXI-depleted plasma. Dabigatran had little effect on ETP at concentrations below 400 ng/mL, whereas in plasma from warfarin-treated patients, ETP was suppressed with INR values over 1.5. CONCLUSIONS: MHV induce thrombin generation via the intrinsic pathway and generate sufficient thrombin to overwhelm clinically relevant dabigatran concentrations. In contrast, warfarin is more effective than dabigatran at suppressing MHV-induced thrombin generation. These data explain why dabigatran failed in MHV patients and suggest that strategies targeting FXII or FXI may suppress the root cause of thrombosis in such patients.


Subject(s)
Anticoagulants/therapeutic use , Antithrombins/therapeutic use , Dabigatran/therapeutic use , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis/adverse effects , Thrombin/metabolism , Thromboembolism/prevention & control , Warfarin/therapeutic use , Anticoagulants/adverse effects , Anticoagulants/blood , Antithrombins/adverse effects , Antithrombins/blood , Dabigatran/adverse effects , Dabigatran/blood , Dose-Response Relationship, Drug , Heart Valve Prosthesis Implantation/instrumentation , Hemorrhage/chemically induced , Humans , International Normalized Ratio , Kinetics , Prosthesis Design , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/etiology , Treatment Outcome , Warfarin/adverse effects , Warfarin/blood
20.
Nat Rev Dis Primers ; 1: 15006, 2015 05 07.
Article in English | MEDLINE | ID: mdl-27189130

ABSTRACT

Venous thromboembolism (VTE) encompasses deep-vein thrombosis (DVT) and pulmonary embolism. VTE is the leading cause of lost disability-adjusted life years and the third leading cause of cardiovascular death in the world. DVT leads to post-thrombotic syndrome, whereas pulmonary embolism can cause chronic pulmonary hypertension, both of which reduce quality of life. Genetic and acquired risk factors for thrombosis include non-O blood groups, factor V Leiden mutation, oral contraceptive use, hormone replacement therapy, advanced age, surgery, hospitalization and long-haul travel. A combination of blood stasis, plasma hypercoagulability and endothelial dysfunction is thought to trigger thrombosis, which starts most often in the valve pockets of large veins. Animal studies have revealed pathogenic roles for leukocytes, platelets, tissue factor-positive microvesicles, neutrophil extracellular traps and factors XI and XII. Diagnosis of VTE requires testing and exclusion of other pathologies, and typically involves laboratory measures (such as D-dimer) and diagnostic imaging. VTE is treated with anticoagulants and occasionally with thrombolytics to prevent thrombus extension and to reduce thrombus size. Anticoagulants are also used to reduce recurrence. New therapies with improved safety profiles are needed to prevent and treat venous thrombosis. For an illustrated summary of this Primer, visit: http://go.nature.com/8ZyCuY.


Subject(s)
Venous Thromboembolism , Venous Thrombosis , Anticoagulants/therapeutic use , Humans , Postthrombotic Syndrome/etiology , Pulmonary Embolism/etiology , Venous Thromboembolism/complications , Venous Thromboembolism/drug therapy , Venous Thromboembolism/mortality , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/mortality
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