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Hematology. American Society of... Nov 2018The majority of patients with venous thromboembolism (VTE) have a considerable long-term risk of recurrence and may require extended duration of anticoagulant treatment... (Review)
Review
The majority of patients with venous thromboembolism (VTE) have a considerable long-term risk of recurrence and may require extended duration of anticoagulant treatment after the initial 3 to 6 months. The decision to extend treatment is based not only on the individual risk of recurrence, but should also consider the potential complications associated with anticoagulation, taking into account that anticoagulant drugs are among the drugs most frequently associated with hospital admission due to adverse drug reactions. The most feared complication of oral anticoagulants is bleeding, which in some cases may be fatal or may affect critical organs. Case-fatality rates of bleeding have been reported to be ∼3 times higher than case-fatality rates of recurrent VTE. Even when nonserious, bleeding may require medical intervention and/or may impact on patient quality of life or working activity. Factors associated with bleeding during anticoagulant treatment include, among others, advanced age, cancer, renal or liver insufficiency, or concomitant antithrombotic drugs, but no bleeding risk score is sufficiently accurate for use in clinical practice. Not uncommonly, bleeding occurs as a complication of trauma or medically invasive procedures. Nonbleeding complications associated with oral anticoagulants are unusual, and their relevance is extremely uncertain, and include vascular calcification, anticoagulation-related nephropathy, and osteoporosis. Finally, because VTE not uncommonly affects young individuals and the mean age of the population is ∼60 years, the costs associated with extended anticoagulation should not be forgotten. The costs of the drugs need to be balanced against health outcome costs associated with both recurrent VTE and bleeding.
Topics: Administration, Oral; Anticoagulants; Humans; Middle Aged; Recurrence; Time Factors; Venous Thromboembolism
PubMed: 30504343
DOI: 10.1182/asheducation-2018.1.432 -
Clinical and Applied... 2023This study evaluated practice patterns and factors influencing treatment decisions regarding urgent or emergent reversal of oral anticoagulants (OACs). A 30-question...
This study evaluated practice patterns and factors influencing treatment decisions regarding urgent or emergent reversal of oral anticoagulants (OACs). A 30-question survey was electronically distributed to anticoagulation members of the Anticoagulation Forum. Questions were designed to capture practice trends in the reversal of warfarin, factor Xa inhibitors, and factor IIa inhibitors. Continuous and categorical data were analyzed to generate descriptive statistics. Open-ended questions were summarized by thematic categories. 173 responses were collected most from US-based pharmacists with direct patient care responsibilities. The majority of the respondents' institutions (90.2%) utilized a guideline or protocol for OACs reversal. Vitamin K (91.3%), activated charcoal (80.4%), and fresh frozen plasma (72.8%) were the most common reversal agents on formulary without restrictions. Most institutions (87.0%) reported having 4-factor prothrombin complex concentrate (4F-PCC) and idarucizumab on formulary, but most commonly (52.2%) with restrictions. Andexanet alfa was only reported on formulary at 35.9% of institutions. In contrast to current guideline recommendations, vitamin K (98.8%) was preferred over 4F-PCC and 4F-PCC (71.6%) was preferred over andexanet alfa as first-line agents used to reverse warfarin and factor Xa inhibitors, respectively. Weight-based dosing strategies for 4F-PCC were commonly utilized for different reversals (41.2%-59.4%). Cost, efficacy, and safety of 4F-PCC were identified as top facilitators and barriers for 4F-PCC adoption in practice. Our findings revealed that guideline recommendations for reversal of warfarin and factor Xa and IIa inhibitors are not followed by a majority of institutions. Studies are needed to investigate strategies to overcome barriers for implementing and following guideline recommendations.
Topics: Humans; Factor Xa Inhibitors; Anticoagulants; Blood Coagulation Factors; Anticoagulant Reversal Agents; Surveys and Questionnaires
PubMed: 37272034
DOI: 10.1177/10760296231176808 -
The Cochrane Database of Systematic... Feb 2020Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the cardiovascular diseases, after coronary artery disease and stroke. The advent of multi-detector computed tomographic pulmonary angiography (CTPA) has allowed better assessment of PE regarding visualisation of the peripheral pulmonary arteries, increasing its rate of diagnosis. More cases of peripheral PEs, such as isolated subsegmental PE (SSPE) and incidental PE, have thereby been identified. These two conditions are usually found in patients with few or none of the classic PE symptoms such as haemoptysis or pleuritic pain, acute dyspnoea or circulatory collapse. However, in patients with reduced cardiopulmonary reserve, classic PE symptoms can be found with isolated SSPEs. Incidental SSPE is found casually in asymptomatic patients, usually by diagnostic imaging performed for other reasons (for example routine CT for cancer staging in oncology patients). Traditionally, all PEs are anticoagulated in a similar manner independent of their location, or number and size of the thrombi. It has been suggested that many patients with SSPE may be treated without benefit, increasing adverse events by a possible unnecessary use of anticoagulants. Patients with isolated SSPE, or incidental PE, may have a more benign clinical presentation compared to those with proximal PEs. However, the clinical significance in patients, and their prognosis, needs to be studied to evaluate whether anticoagulation therapy is required. This is the second update of the Cochrane systematic review published in 2014.
OBJECTIVES
To assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 November 2019. We also undertook reference checking to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials of anticoagulation therapy versus control in patients with SSPE or incidental SSPE.
DATA COLLECTION AND ANALYSIS
Two review authors inspected all citations identified to ensure reliable assessment. If relevant studies were identified, we planned for two review authors to independently extract data and to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We did not identify any studies that met the inclusion criteria.
AUTHORS' CONCLUSIONS
There is no evidence from randomised controlled trials to assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE. Well-conducted research is required before informed practice decisions can be made.
Topics: Acute Disease; Anticoagulants; Dyspnea; Humans; Prognosis; Pulmonary Embolism; Randomized Controlled Trials as Topic; Treatment Outcome; Watchful Waiting
PubMed: 32030721
DOI: 10.1002/14651858.CD010222.pub4 -
Vascular Medicine (London, England) Apr 2015Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the... (Review)
Review
Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the initial 3-month window involves assessing a combination of risk factors for VTE recurrence and bleeding, along with weighing patient preferences. In some cases, such as VTE provoked by a reversible surgical risk factor, the recurrence risk is sufficiently low that most patients should not receive extended therapy. In other cases, such as VTE associated with malignancy, the recurrence risk is sufficiently high that treatment should be extended beyond the initial 3 months. However, a large number of patients fall into a grey zone where the decision on extended therapy is less clear-cut. In this review, we summarize the evidence for VTE recurrence risk and the role for extended anticoagulation given a variety of patient-specific factors and laboratory results. We also review the role of VTE risk prediction tools and provide a recommended algorithm for approaching the decision of extended anticoagulation therapy. Various agents available for extended VTE therapy, including warfarin, aspirin and the direct oral anticoagulant agents, are discussed.
Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Recurrence; Risk Factors; Time Factors; Venous Thromboembolism; Warfarin
PubMed: 25832602
DOI: 10.1177/1358863X14566429 -
British Journal of Haematology Oct 2011The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing... (Review)
Review
The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.
Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin; beta-Alanine
PubMed: 21848880
DOI: 10.1111/j.1365-2141.2011.08826.x -
Clinical Transplantation Jan 2017For more than 60 years, warfarin was the only oral anticoagulation agent available for use in the United States. In many recent clinical trials, several direct oral... (Review)
Review
For more than 60 years, warfarin was the only oral anticoagulation agent available for use in the United States. In many recent clinical trials, several direct oral anticoagulants (DOACs) demonstrated similar efficacy with an equal or superior safety profile, with some other notable benefits. The DOACs have lower inter- and intrapatient variability, much shorter half-lives, and less known drug-drug and drug-food interactions as compared to warfarin. Despite these demonstrated benefits, the use of DOACs has not gained uniform acceptance because of lack of supportive data in special patient populations, including recipients of solid organ transplants maintained on immunosuppression. This review describes the properties of several novel DOACs including their pharmacology and mechanisms of action as they relate to use among solid organ transplant recipients. We have particularly focused on (i) dosing in patients with impaired renal and hepatic function; (ii) considerations for drug-drug interactions with immunosuppressive medications; and (iii) management of the anticoagulated patients at the time of unplanned surgery. The risks and benefits of the use of DOACs in solid organ transplant recipients should be carefully evaluated prior to the introduction of these agents in this highly distinct patient population.
Topics: Administration, Oral; Anticoagulants; Graft Rejection; Humans; Organ Transplantation
PubMed: 27859621
DOI: 10.1111/ctr.12873 -
Cleveland Clinic Journal of Medicine Apr 2015Most patients who suffer a hemorrhage while on long-term anticoagulant therapy continue to be at risk of thrombosis. Physicians often need to reconsider the need for... (Review)
Review
Most patients who suffer a hemorrhage while on long-term anticoagulant therapy continue to be at risk of thrombosis. Physicians often need to reconsider the need for anticoagulation in view of the risk of recurrent bleeding, and when anticoagulation needs to be resumed, they must also consider the timing and strategy. Since there are no evidence-based guidelines for these situations, the authors of this paper offer a practical framework for individualizing the resumption of anticoagulation after hemorrhage.
Topics: Anticoagulants; Gastrointestinal Hemorrhage; Global Health; Humans; Incidence; Practice Guidelines as Topic; Risk Factors; Thromboembolism; Withholding Treatment
PubMed: 25955459
DOI: 10.3949/ccjm.82a.14047 -
Shock (Augusta, Ga.) Aug 2017Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist... (Review)
Review
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development.Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal.The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies.
Topics: Administration, Oral; Animals; Anticoagulants; Antidotes; Blood Coagulation Factors; Disease Models, Animal; Hemorrhage; Humans
PubMed: 28471371
DOI: 10.1097/SHK.0000000000000848 -
The American Journal of Emergency... Nov 2016Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient... (Review)
Review
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures. These include general stopping rules (such as ≥24 hours for low-risk procedures and ≥48 hours for high-risk surgery with normal renal function) for elective procedures. Bridging therapy when oral anticoagulant treatment is interrupted has recently been questioned, depending on the clinical scenario. Novel agents for the reversal of DOAC-induced anticoagulation have recently been developed. Idarucizumab, a humanized monoclonal antibody fragment that selectively binds dabigatran, was recently approved for clinical use in patients with life-threatening or uncontrolled bleeding, and for patients requiring emergency interventions. Idarucizumab can streamline the pre- and periprocedural anticoagulation management of dabigatran-treated patients, as it provides fast, complete, and sustainable reversibility. Andexanet alfa is an inactive, decoy factor Xa (FXa) molecule that binds FXa inhibitors, and ciraparantag is a synthetic molecule designed to bind fractionated and unfractionated heparins, and each of the currently approved DOACs. As clinical development of the additional anti-FXa-specific anticoagulant reversal agents proceeds, the respective role of each in the management of emergency bleeding events and invasive procedures will be better defined, and it is hoped they will make important contributions to patient care.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Blood Coagulation Tests; Emergency Treatment; Factor Xa; Hemorrhage; Humans; Perioperative Care; Piperazines; Recombinant Proteins; Withholding Treatment
PubMed: 27697442
DOI: 10.1016/j.ajem.2016.09.048 -
The American Journal of Medicine Nov 2016Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient... (Review)
Review
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures. These include general stopping rules (such as ≥24 hours for low-risk procedures and ≥48 hours for high-risk surgery with normal renal function) for elective procedures. Bridging therapy when oral anticoagulant treatment is interrupted has recently been questioned, depending on the clinical scenario. Novel agents for the reversal of DOAC-induced anticoagulation have recently been developed. Idarucizumab, a humanized monoclonal antibody fragment that selectively binds dabigatran, was recently approved for clinical use in patients with life-threatening or uncontrolled bleeding, and for patients requiring emergency interventions. Idarucizumab can streamline the pre- and periprocedural anticoagulation management of dabigatran-treated patients, as it provides fast, complete, and sustainable reversibility. Andexanet alfa is an inactive, decoy factor Xa (FXa) molecule that binds FXa inhibitors, and ciraparantag is a synthetic molecule designed to bind fractionated and unfractionated heparins, and each of the currently approved DOACs. As clinical development of the additional anti-FXa-specific anticoagulant reversal agents proceeds, the respective role of each in the management of emergency bleeding events and invasive procedures will be better defined, and it is hoped they will make important contributions to patient care.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Antithrombins; Arginine; Dabigatran; Deprescriptions; Emergencies; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Piperazines; Prothrombin Time; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Surgical Procedures, Operative
PubMed: 27569675
DOI: 10.1016/j.amjmed.2016.06.005