Advances in Therapy and the Management of Antithrombotic Drugs for Venous Thromboembolism

Hematology ◽  
2000 ◽  
Vol 2000 (1) ◽  
pp. 266-284
Author(s):  
Jack E. Ansell ◽  
Jeffrey I. Weitz ◽  
Anthony J. Comerota
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Venous Thrombosis ◽  
Tissue Factor ◽  
Oral Anticoagulants ◽  
Diverse Range ◽  
Anticoagulant Drugs ◽  
Wide Range ◽  
The Impact ◽  
Block Factor

Abstract This review focuses on antithrombotic therapy for venous thromboembolism and covers a diverse range of topics including a discussion of emerging anticoagulant drugs, a renewed focus on thrombolytic agents for selected patients, and an analysis of the factors leading to adverse events in patients on warfarin, and how to optimize therapy. In Section I Dr. Weitz discusses new anticoagulant drugs focusing on those that are in the advanced stages of development. These will include drugs that (a) target factor VIIa/tissue factor, including tissue factor pathway inhibitor and NAPc2; (b) block factor Xa, including the synthetic pentasaccharide and DX9065a; (c) inhibit factors Va and VIIIa, i.e., activated protein C; and (d) block thrombin, including hirudin, argatroban, bivalirudin and H376/95. Oral formulations of heparin will also be reviewed. In Section II, Dr. Comerota will discuss the use of thrombolysis for selected patients with venous thromboembolism. Fibrinolytic therapy, which has suffered from a high risk/benefit ratio for routine deep venous thrombosis, may have an important role to play in patients with iliofemoral venous thrombosis. Dr. Comerota presents his own results with catheter-directed thrombolytic therapy and the results from a large national registry showing long-term outcomes and the impact on quality of life. In Section III, Dr. Ansell presents a critical analysis of the factors responsible for adverse events with oral anticoagulants and the optimum means of improving outcomes. The poor status of present day anticoagulant management is reviewed and the importance of achieving a high rate of “time in therapeutic range,” is emphasized. Models of care to optimize outcomes are described, with an emphasis on models that utilize patient self-testing and patient self-management of oral anticoagulation which are considered to be the ultimate in anticoagulation care. The treatment of venous and arterial thromboembolism is undergoing rapid change with respect to the development of new antithrombotic agents, an expanding list of new indications, and new methods of drug delivery and management. In spite of these changes, many of the traditional therapeutics are still with us and continue to play a vital role in the treatment of thromboembolic disease. The following discussion touches on a wide range of therapeutic interventions, from old to new, exploring the status of anticoagulant drug development, describing a new intervention for iliofemoral venous thrombosis, and analyzing the critical factors for safe and effective therapy with oral anticoagulants.

Advances in Therapy and the Management of Antithrombotic Drugs for Venous Thromboembolism

Hematology ◽  
2000 ◽  
Vol 2000 (1) ◽  
pp. 266-284
Author(s):  
Jack E. Ansell ◽  
Jeffrey I. Weitz ◽  
Anthony J. Comerota
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Venous Thrombosis ◽  
Tissue Factor ◽  
Oral Anticoagulants ◽  
Diverse Range ◽  
Anticoagulant Drugs ◽  
Wide Range ◽  
The Impact ◽  
Block Factor

This review focuses on antithrombotic therapy for venous thromboembolism and covers a diverse range of topics including a discussion of emerging anticoagulant drugs, a renewed focus on thrombolytic agents for selected patients, and an analysis of the factors leading to adverse events in patients on warfarin, and how to optimize therapy. In Section I Dr. Weitz discusses new anticoagulant drugs focusing on those that are in the advanced stages of development. These will include drugs that (a) target factor VIIa/tissue factor, including tissue factor pathway inhibitor and NAPc2; (b) block factor Xa, including the synthetic pentasaccharide and DX9065a; (c) inhibit factors Va and VIIIa, i.e., activated protein C; and (d) block thrombin, including hirudin, argatroban, bivalirudin and H376/95. Oral formulations of heparin will also be reviewed.In Section II, Dr. Comerota will discuss the use of thrombolysis for selected patients with venous thromboembolism. Fibrinolytic therapy, which has suffered from a high risk/benefit ratio for routine deep venous thrombosis, may have an important role to play in patients with iliofemoral venous thrombosis. Dr. Comerota presents his own results with catheter-directed thrombolytic therapy and the results from a large national registry showing long-term outcomes and the impact on quality of life.In Section III, Dr. Ansell presents a critical analysis of the factors responsible for adverse events with oral anticoagulants and the optimum means of improving outcomes. The poor status of present day anticoagulant management is reviewed and the importance of achieving a high rate of “time in therapeutic range,” is emphasized. Models of care to optimize outcomes are described, with an emphasis on models that utilize patient self-testing and patient self-management of oral anticoagulation which are considered to be the ultimate in anticoagulation care. The treatment of venous and arterial thromboembolism is undergoing rapid change with respect to the development of new antithrombotic agents, an expanding list of new indications, and new methods of drug delivery and management. In spite of these changes, many of the traditional therapeutics are still with us and continue to play a vital role in the treatment of thromboembolic disease. The following discussion touches on a wide range of therapeutic interventions, from old to new, exploring the status of anticoagulant drug development, describing a new intervention for iliofemoral venous thrombosis, and analyzing the critical factors for safe and effective therapy with oral anticoagulants.

Comparison Of Drugs in Patients Using New Generation Anticoagulants

2021 ◽  
Vol 6 (14) ◽  
pp. 56-67
Author(s):  
Arslan Say ◽  
Abdülkadir ÇAKMAK ◽  
Gökhan KESKİN ◽  
Erdinç PELİT ◽  
Yılmaz ÖZBAY
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Recurrent Venous Thromboembolism ◽  
Anticoagulant Drugs ◽  
History Of ◽  
The Mean ◽  
N 93 ◽  
New Generation

Aim: New generation anticoagulants rapidly find a wider area of use in the clinic due to the use problems of other oral anticoagulants. Anticoagulants such as Dabigatran, Rivaroxaban, and Apixaban with safer treatment intervals have been accepted in clinical practice guidelines and have taken their place as preferred drugs. In this study, we aimed to retrospectively examine the effects of three new-generation anticoagulant drugs on a group of patients. Material and Methods: In this retrospectively planned study, patients diagnosed with atrial fibrillation (n = 522) were divided into three groups according to the drugs used for treatment (Dabigatran, Rivaroxaban, and Apixaban). Routine blood values of the patients in each group were retrospectively scanned according to age, gender, time of drug initiation and presence of chronic disease. Results: According to the results obtained, it was found that the mean HCT, BUN, AST, ALT, MPV, Iron, and Ferritin were higher in patients using Apixaban than those using Dabigatran and Rivaroxaban drugs, but the age, average values of Hgb1 Hgb2, Hgb1, PLT, CrCl, Gfr and INR of the patients using Apixaban lower than those using Dabigatran and Rivaroxaban. The highest rate (22.5%) was found in the group of patients taking apixaban (n=93) when people taking the drugs were examined in terms of mortality. Conclusion: It has been observed that Rivaroxaban can be used more safely in patients with a history of acute cancer and thrombosis, patients with recurrent venous thromboembolism, and patients with high frailty, three drugs should be preferred instead of oral anticoagulants.

Temporal trends in pharmacologic prophylaxis for venous thromboembolism after hip and knee replacement in older adults

2020 ◽  
Vol 25 (5) ◽  
pp. 450-459
Author(s):  
Darae Ko ◽  
Alok Kapoor ◽  
Adam J Rose ◽  
Amresh D Hanchate ◽  
Donald Miller ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Knee Replacement ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Temporal Trends ◽  
Major Hemorrhage ◽  
Vte Prophylaxis ◽  
Physician Review ◽  
Pharmacologic Prophylaxis

Trends in prescription for venous thromboembolism (VTE) prophylaxis following total hip (THR) and knee replacement (TKR) since the approval of direct oral anticoagulants (DOACs) and the 2012 guideline endorsement of aspirin are unknown, as are the risks of adverse events. We examined practice patterns in the prescription of prophylaxis agents and the risk of adverse events during the in-hospital period (the ‘in-hospital sample’) and 90 days following discharge (the ‘discharge sample’) among adults aged ⩾ 65 undergoing THR and TKR in community hospitals in the Institute for Health Metrics database over a 30-month period during 2011 to 2013. Eligible medications included fondaparinux, DOACs, low molecular weight heparin (LMWH), other heparin products, warfarin, and aspirin. Outcomes were validated by physician review of source documents: VTE, major hemorrhage, cardiovascular events, and death. The in-hospital and the discharge samples included 10,503 and 5722 adults from 65 hospitals nationwide, respectively (mean age 73, 74 years; 61%, 63% women). Pharmacologic prophylaxis was near universal during the in-hospital period (93%) and at discharge (99%). DOAC use increased substantially and was the prophylaxis of choice for nearly a quarter (in-hospital) and a third (discharge) of the patients. Aspirin was the sole discharge prophylactic agent for 17% and 19% of patients undergoing THR and TKR, respectively. Warfarin remained the prophylaxis agent of choice for patients aged 80 years and older. The overall risk of adverse events was low, at less than 1% for both the in-hospital and discharge outcomes. The low number of adverse events precluded statistical comparison of prophylaxis regimens.

scholarly journals Preoperative nutritional factors and outcomes after radical cystectomy: A narrative review

2017 ◽  
Vol 11 (12) ◽  
pp. 419-24
Author(s):  
Janie Allaire ◽  
Tal Ben-Zvi ◽  
Benoît Lamarche ◽  
Karine Robitaille ◽  
Yves Fradet ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Nutritional Status ◽  
Radical Cystectomy ◽  
Mortality Risk ◽  
Prospective Studies ◽  
Intervention Studies ◽  
Narrative Review ◽  
Nutritional Factors ◽  
The Impact

Only a few nutritional factors have been identified to predict the risk of developing complications after radical cystectomy (RC). This narrative review delineates the current known effects of preoperative nutritional status factors in this context. The report highlights the heterogeneity between study methods and results. We determined that low albuminemia values increase mortality risk and overall complications. In addition, obesity tends to increase the risk of developing venous thromboembolism and adverse events. Additional prospective studies, using standardized methods to both define and report complications, should be conducted to strengthen the connections between preoperative nutritional status factors and post-RC complications. Furthermore, intervention studies testing the impact of strategies to improve nutritional status on the risk of complications after RC are also needed.

scholarly journals Accredited Interactive Web-Based Application for the 2016 International Clinical Practice Guidelines on Thrombosis in Cancer: Improving Knowledge Transfer in Daily Clinical Practice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5954-5954
Author(s):  
Dominique Farge
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Web Based ◽  
Patients With Cancer ◽  
The Impact

Abstract Venous thromboembolism (VTE) is a major therapeutic concern in cancer patients and the leading cause of death after metastasis. Providing anticoagulant therapy to this patient population is challenging because cancer patients are at increased risk of VTE recurrence and bleeding, and treatment management is often complicated by other co-morbidities that affect choice of anticoagulation. The International Initiative on Thrombosis and Cancer (ITAC-CME) is a multidisciplinary group of International academic clinicians, researchers, and experts dedicated to reducing the global burden of VTE and its consequences in cancer patients. In 2013, the group published international clinical practice guidelines for the treatment and prophylaxis of VTE in cancer (1, 2). In collaboration with CME solutions, an accredited CME provider, ITAC-CME developed a mobile web-based application to promote the international implementation of the 2013 guidelines, in English and French (www.itacc-cme.org). Usage of the app has steadily increased every year since its release. ITAC-CME recently revised its consensus recommendations according to a systematic review of the literature up to January 2016. In particular, the ISTH-endorsed updated recommendations provide a guidance on the use of the direct oral anticoagulants based on the current level of evidence (3). ITAC-CME and CME solutions have updated the web-based application to support the 2016 guidelines. The app also includes several new features, including interactive case-based CME learning activities, with pre- and post-activity practice assessments. These pre- and post-test metrics will be documented to record international clinical practice patterns, and monitor the impact of the app on the adoption of the 2016 guidelines into clinical practice worldwide. Translation of the 2016 updated app into additional languages is planned. The application has been submitted for accreditation with the royal College of Physicians and surgeons of Canada, the American Medical Association, the European Union of Medical Specialists, l' Organisme Gestionnaire du Développement Professionnel Continu, and the European Board for Accreditation in Hematology. 1 Debourdeau P, Farge D, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Büller HR, Bounameaux H. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):71-80. 2 Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.J Thromb Haemost. 2013 Jan;11(1):56-70 3 Farge D, Bounameaux H , Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A. 2016 International Clinical Practice Guidelines Including Guidance for the Direct Oral Anticoagulants in the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Onccology 2016 (in press) Disclosures No relevant conflicts of interest to declare.

Prothrombin Fragment F1+2 Is not Predictive for Recurrent Venous Thromboembolism

1997 ◽  
Vol 77 (05) ◽  
pp. 0829-0833 ◽  
Author(s):  
P A Kyrle ◽  
S Eichinger ◽  
I Pabinger ◽  
A Stümpflen ◽  
M Hirschl ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Protein C ◽  
Oral Anticoagulants ◽  
Factor V Leiden ◽  
Factor V ◽  
Recurrent Thrombosis ◽  
Prothrombin Fragment ◽  
Recurrent Venous Thromboembolism ◽  
History Of

SummaryIt would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable.We investigated the value of prothrombin fragment Fl+2 (FI+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the Fl+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and Fl+2 was measured at regular intervals.Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in Fl+2 levels was found in patients with and without recurrent thrombosis. Fl+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, Fl+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in Fl+2 was seen between patients with and without Factor V Leiden.We conclude that monitoring of Fl+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

Approaches to Macrofinancial Surveillance in Article IV Reports

Policy Papers ◽  
2017 ◽  
Vol 17 (13) ◽  
Author(s):  
Keyword(s):  
Low Income ◽  
Global Financial Crisis ◽  
Financial Sector ◽  
Policy Advice ◽  
Low Income Countries ◽  
Financial Shocks ◽  
Diverse Range ◽  
The Past ◽  
Wide Range ◽  
The Impact

The Fund has made good progress over the past two years in integrating macrofinancial analysis into Article IV surveillance for a wide range of members. Building on past work to enhance financial sector analysis, Fund staff has sought to develop a consistent and forward-looking view on how the financial sector affects each member’s economic outlook with the aim of strengthening staff’s capacity to provide advice on macro-critical questions. The focus has been on developing a fuller understanding of macrofinancial linkages, and applying this analysis to inform policy advice. Staff has sought to articulate the role of the financial sector in the macroeconomic baseline, and to integrate the financial sector into the risk assessment, taking into account both the impact of macro shocks on the financial sector as well as the effect of financial shocks on macroeconomic stability. Strengthening the analytical foundations of this work has helped staff provide advice in all policy areas, including financial sector policies. Staff has tailored macrofinancial analysis to the circumstances of a diverse set of economies. Area departments have taken the lead in selecting 66 economies for enhanced macrofinancial coverage and in identifying topics, drawing on targeted support from functional departments. The choice of coverage has included legacies from the global financial crisis—such as deleveraging and stretched balance sheets in advanced economies and some emerging markets—and more recent challenges such as commodity price shocks, especially in low income countries, and the risks of housing booms. The financial sector’s contribution to growth and inclusion has become an important question in countries across all income groups. Staff sees benefits in mainstreaming this approach across the membership, while continuing to address analytical gaps and adapting to new challenges. The work of the past two years has underscored the criticality of macrofinancial analysis for a diverse range of members, and laid the basis for progressively mainstreaming macrofinancial surveillance across the membership. Building on this progress, staff sees scope for the Fund to deepen its understanding of the macroeconomic effects of financial shocks, to better adapt microprudential and macroprudential policy advice with an assessment of macro-critical risks including systemic risk, and to deepen the analysis of outward spillovers. Staff will also need to continue to adapt the focus of analysis and tools, and seek relevant data, as economic challenges evolve.

scholarly journals Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients

2020 ◽  
Vol 26 ◽  
pp. 107602962090915 ◽  
Author(s):  
Mario Rojo ◽  
Angela Margarita Roco ◽  
Marcelo Suarez ◽  
Maria Alejandra Lavanderos ◽  
Gabriel Verón ◽  
...  
Keyword(s):  
Adverse Events ◽  
Therapeutic Range ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Cardiovascular Patients ◽  
Oral Agents ◽  
Related Variant ◽  
Ethnic Variations ◽  
The Impact

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 ( rs4244285), CYP1A2*1F ( rs762551), GGCx ( rs11676382), CYP2C9*2 ( rs1799853), CYP2C9*3 ( rs1057910), CYP4F2 ( rs2108622), VKORC1 ( rs9923231), VKORC1 ( rs7294), CYP3A4*1B ( rs2740574), and ABCB1 ( rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.

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