scholarly journals Emerging anticoagulant strategies

Blood ◽  
2017 ◽  
Vol 129 (2) ◽  
pp. 147-154 ◽  
Author(s):  
James C. Fredenburgh ◽  
Peter L. Gross ◽  
Jeffrey I. Weitz
Keyword(s):  
Secondary Prevention ◽  
Venous Thrombosis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Strategies ◽  
Arterial Injury ◽  
Standards Of Care ◽  
Factor Xii ◽  
New Anticoagulants ◽  
Novel Treatment Strategies

Abstract Despite the introduction of direct oral anticoagulants (DOACs), the search for more effective and safer antithrombotic strategies continues. Better understanding of the pathogenesis of thrombosis has fostered 2 new approaches to achieving this goal. First, evidence that thrombin may be as important as platelets to thrombosis at sites of arterial injury and that platelets contribute to venous thrombosis has prompted trials comparing anticoagulants with aspirin for secondary prevention in arterial thrombosis and aspirin with anticoagulants for primary and secondary prevention of venous thrombosis. These studies will help identify novel treatment strategies. Second, emerging data that naturally occurring polyphosphates activate the contact system and that this system is critical for thrombus stabilization and growth have identified factor XII (FXII) and FXI as targets for new anticoagulants that may be even safer than the DOACs. Studies are needed to determine whether FXI or FXII is the better target and to compare the efficacy and safety of these new strategies with current standards of care for the prevention or treatment of thrombosis. Focusing on these advances, this article outlines how treatment strategies for thrombosis are evolving and describes the rationale and approaches to targeting FXII and FXI. These emerging anticoagulant strategies should address unmet needs and reduce the systemic underuse of anticoagulation because of the fear of bleeding.

scholarly journals Novel antithrombotic strategies for treatment of venous thromboembolism

Blood ◽  
2020 ◽  
Vol 135 (5) ◽  
pp. 351-359 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Noel C. Chan
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Postthrombotic Syndrome ◽  
Factor Xii ◽  
Factor Xi ◽  
Vein Thrombosis ◽  
New Anticoagulants

Abstract Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cause of vascular death after heart attack and stroke. Anticoagulation therapy is the cornerstone of VTE treatment. Despite such therapy, up to 50% of patients with DVT develop postthrombotic syndrome, and up to 4% of patients with PE develop chronic thromboembolic pulmonary hypertension. Therefore, better therapies are needed. Although direct oral anticoagulants are more convenient and safer than warfarin for VTE treatment, bleeding remains the major side effect, particularly in cancer patients. Factor XII and factor XI have emerged as targets for new anticoagulants that may be safer. To reduce the complications of VTE, attenuation of thrombin activatable fibrinolysis inhibitor activity is under investigation in PE patients to enhance endogenous fibrinolysis, whereas blockade of leukocyte interaction with the vessel wall is being studied to reduce the inflammation that contributes to postthrombotic syndrome in DVT patients. Focusing on these novel antithrombotic strategies, this article explains why safer anticoagulants are needed, provides the rationale for factor XII and XI as targets for such agents, reviews the data on the factor XII– and factor XI–directed anticoagulants under development, describes novel therapies to enhance fibrinolysis and decrease inflammation in PE and DVT patients, respectively, and offers insights into the opportunities for these novel VTE therapies.

scholarly journals Cerebral Venous Thrombosis: Reviewing Pathophysiology, Diagnosis, and Treatment Strategies

2019 ◽  
Vol 06 (02) ◽  
pp. 140-144 ◽  
Author(s):  
Yasmin A. O'Keefe ◽  
Peter G. Kranz ◽  
Keith E. Dombrowski ◽  
Brad J. Kolls ◽  
Michael L. James
Keyword(s):  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Strategies ◽  
Venous Drainage ◽  
Diagnosis And Treatment ◽  
Cerebral Veins ◽  
Heparin Infusion ◽  
Newer Anticoagulants

AbstractThis review discusses cerebral venous thrombosis (CVT), including diagnosis and treatment strategies, a rare class of stroke that, if unrecognized or untreated, can have devastating effects. Thrombosis of one or many cerebral veins leads to propagation of thrombosis and impaired cerebral venous drainage. Diagnosis is made using a combination of history and imaging, particularly computed tomography (CT) venogram, which demonstrates thrombosis. Currently, acute treatment consists of heparin infusion with transition to long-term oral anticoagulation. Further research, especially on prevention, endovascular therapy, and the role of newer anticoagulants (direct oral anticoagulants [DOACs]) is necessary and ongoing.

scholarly journals Cerebral Venous Thrombosis Case Series at a Tertiary Care Hospital: Exploring Treatment Safety and Efficacy of Direct Oral Anticoagulants

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3658-3658
Author(s):  
Mohammed Abdullah Alsheef ◽  
Mukhtar Alomar ◽  
Abdul Rehman Z. Zaidi ◽  
Ghaydaa Juma Kullab ◽  
Mohammed AlHazzaa ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Tertiary Care ◽  
Case Series ◽  
Case Report Form ◽  
Care Hospital ◽  
Safety And Efficacy ◽  
Number Of Patients

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults and children. Initial treatment with heparin followed by wafarin is the mainstay of treatment. Only insufficient experience is available for direct oral anticoagulants (DOACs). Aims: The study aims to demonstrate the efficacy and safety of DOACs such as (Rivaroxaban and Dabigatran) in patients with objectively confirmed CVT. Methods: Data of 46 cases of CVT collected using a standardized case report form. Inclusion criteria were patients diagnosed with CVT, confirmed by CT or MRI imaging. Results: The total number of patients was 46 (9 males and 37 females). The mean age of the patients was 35.2± 5 years. The most common clinical manifestations among our patients were headache followed by seizure. 52% of cases were unprovoked, while 48% were provoked by pregnancy and oral contraceptive pills. Superior sagittal sinus (55%) and transverse sinus (44.9%) were the most common sites. Involvement of more than three venous sinuses was 34.8%. Thrombophilic abnormality was detected in 21.7% of patients. Initiation of anticoagulation (AC) was mostly low molecular weight heparin (LMWH) (80%), followed by unfractionated heparin (UFH) (17.7%) and fondaparinex (2%). Maintenance AC with Rivaroxaban after heparin (LMWH/UFH) was in 63% of our patients, the rest were switched from Warfarin to Rivaroxaban (34.8%), and one was treated by Dabigatran (2%). CVT recurrence was observed in one patient. Major bleeding (according to ISTH criteria) was not reported in our case series. Conclusions: DOACs demonstrated good safety and efficacy profile and can potentially replace warfarin in CVT patients. Disclosures No relevant conflicts of interest to declare.

Abstract 15444: Anticoagulation Treatment of Venous Thromboembolism Across the Weight Spectrum: Insights From the Veterans Health Administration

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexander C Perino ◽  
Jun Fan ◽  
Mitra Kothari ◽  
ATIF MOHAMMAD ◽  
Patrick Hlavacek ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Strategies ◽  
Veterans Health ◽  
Health Administration ◽  
Mechanical Valves ◽  
Consensus Statements ◽  
Body Weights ◽  
Va Health Care System

Introduction: In seminal trials of venous thromboembolism (VTE) treatment with direct oral anticoagulants (DOAC), few patients were enrolled at low and high body weights to estimate treatment effects in these subgroups. Consensus statements have recommended against use of DOACs in VTE for patients ≥120 kg. We sought to describe real-world use of DOACs and other anticoagulants for VTE across the weight spectrum. Methods: We performed a retrospective cohort study of patients with first-time VTE that were treated with anticoagulants in the VA health care system from 2008 to 2018. We excluded patients with 1) additional indications for anticoagulation (atrial fibrillation and mechanical valves) and 2) no documented weight in the 90 days prior to 90 days after index VTE. We stratified patients by weight (<60, 60 to 119, ≥120 kg) and determined 1) index anticoagulation prescription in the 30 days after index VTE (DOAC, warfarin, and low molecular weight heparin or fondaparinux [LMWH/F] only) and 2) variables associated with DOAC prescription, as compared to warfarin, in those ≥120 kg. Results: After excluding 3,676 patients with missing weight, there were 111,774 patients with VTE (64±13 years, 6% female). The most common therapy was warfarin (66%), followed by DOAC (21%), and LMWH/F only (13%). Median weight was 92 kg (interquartile range: 28), with 13,753 patients (12%) with weight ≥120 kg. Across weight categories, proportion of patients receiving DOAC was similar. In patients ≥120 kg, after multivariate adjustment, multiple comorbidities were associated with warfarin prescription while chronic kidney disease was associated with DOAC prescription ( Table ). Conclusion: Weight ≥120 kg is common for VTE patients, with DOAC frequently prescribed despite consensus statements recommending DOAC avoidance. For patients ≥120 kg, comorbidities influence VTE treatment selection, and determination of optimal treatment strategies across the spectrum of comorbidities is needed.

scholarly journals Cancer and Embolic Stroke of Undetermined Source

Stroke ◽  
2021 ◽  
Author(s):  
Babak B. Navi ◽  
Scott E. Kasner ◽  
Mitchell S.V. Elkind ◽  
Mary Cushman ◽  
Oh Young Bang ◽  
...  
Keyword(s):  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Strategies ◽  
Distant Metastases ◽  
Embolic Stroke ◽  
Cancer Treatments ◽  
Management Plans ◽  
Novel Biomarkers ◽  
Individualized Management

One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.

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