Chest Physicians Consensus Conference Research Articles

Anticoagulation Clinical Pharmacist: Anticoagulation Care between the Headset and the Dial Pad

Anticoagulant is a class of medication that saves lives while carries an intrinsic risk of harm. The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy for the first time in 1995 endorsed the setting of specialized anticoagulation clinics instead of usual medical care. Recently telemedicine is not a brand-new method of patient care, yet, telemedicine utilization has increased dramatically during the last year to comply with the curfew that most cities of the world had to apply to reduce the spread of COVID-19. Telemedicine and especially anticoagulation care need careful systems, the minimum infrastructure of patient records including telephone contact number, facility telephone, and clinic appointment system. The top three challenges when applying telehealth are payment, confidentiality, and un-updated patients’ information.

Phlegmasia cerulea dolens complicated by methylenetetrahydrofolate reductase genetic mutation

Introduction: Deep venous thrombosis (DVt) is the formation of a blood clot within a deep vein. Phlegmasia cerulea dolens (PcD) represents a critical acute consequence of DVt. the PcD is a condition caused by massive iliofemoral thrombosis that produces severe venous congestion and obstruction of arterial flow; eventually, causing ischemia in the affected extremity. the treatment goals of PcD are to restore venous outflow by removing thrombus burden, prevent additional thrombus formation, and maintain collateral circulation. However, no therapeutic algorithms exist for PcD. case report: We report PcD in a 55-year-old male with a significant past medical history for multiple venous thromboembolisms, requiring placement of an inferior vena cava filter and lifetime anticoagulation. clinical presentation and accompanying venous duplex results led to the diagnosis of PcD. the 9th American college of chest Physicians consensus conference on Antithrombotic and thrombolytic therapy created guidelines for treatment of acute DVt in the absence of gangrene. Guidelines advise to withhold thrombolysis and percutaneous

Venous Thromboembolic Complications in Colorectal Surgery.

See Article on Page 187-191 Colorectal patients who undergo radical surgery are vulnerable to the development of a venous thromboembolism (VTE). A VTE and a pulmonary embolism (PE) can result in chronic leg swelling, ulceration, and discomfort (postthrombotic syndrome), or even death [1]. A number of factors that increase the risk of a postoperative VTE have been identified. In addition to the surgical procedure itself, these include a history of previous VTE, cancer, inflammatory bowel disease, thrombophilia, old age, obesity, smoking, acute illness, wound infection, and prolonged immobilization [2,3,4]. Therefore, interest exists in better characterizing the specific risk factors for a VET, especially a PE, in patients undergoing colorectal surgery. This could help determine strategies for preventing a VTE, as well as PE, in this complex patient population. Furthermore, questions remain regarding the optimal duration of prophylaxis, patient selection, and the real effect of VTE prophylaxis. Although multiple trials have demonstrated the efficacy of VTE prophylaxis, a number of reports have also suggested that perioperative VTE prophylaxis is underutilized in clinical practice. The prospective United States VTE Free Study reported that less than one half of the 1,375 patients who had undergone nonorthopedic surgeries and had developed an ultrasound-confirmed VTE had received VTE prophylaxis [5]. In addition, the American College of Chest Physicians Consensus Conference on Antithrombotic Therapy found a VTE prophylaxis compliance of only 13% [6]. Extended VTE prophylaxis has the potential to negatively influence patient outcomes and may actually lead to bleeding complications in the immediate postoperative period. Surgeons may also be more reluctant to perform imaging procedures when the patient's condition is questionable. Recent prospective data showed the lack of any benefit from an aggressive VTE prevention strategy; among 16,120 patients undergoing colorectal surgery, the use of perioperative and in-hospital VTE prophylaxis increased significantly from 32% to 86% and from 60% to 91%, respectively, between 2006 and 2011 [7]. Despite this increase, no change in the VTE rates was observed over time. The overall incidence of a VTE remained low, at 2.2%. Another recent study from 2,838 hospitals in the United States indicated that hospitals with characteristics suggestive of higher quality (e.g., more accreditations) had higher VTE chemoprophylaxis rates, but paradoxically had worse risk-adjusted VTE rates [8]. Therefore, VTE rates seem to be influenced more by the utilization rates for hospital VTE imaging than by adherence to VTE prevention strategies. Based on emerging evidence, further investigations of VTE chemoprophylaxis in patients undergoing colorectal surgery, by using a nation-wide study in Korea, may be necessary. These results may influence future studies looking specifically at prophylaxis guidelines.

Editorial introductions

Editorial introductions

Editorial introductions

Editorial introductions

AN EVALUATION OF THE LONG-TERM TREATMENT OF VENOUS THROMBOEMBOLISM IN HOSPITALIZED CANCER PATIENTS

PURPOSE: Studies have shown that long-term treatment with subcutaneous (SC) low-molecular-weight-heparin (LMWH) is more effective than vitamin-K-antagonist (VKA) therapy for preventing recurrent venous-thromboembolism-events (VTE) in cancer patients with VTE. The Sixth American College of Chest Physicians (ACCP) Consensus Conference (2004) recommends that patients with cancer and VTE be treated with SC-LMWH for at least six months. Our main objective was to characterize the long-term VTE treatment strategies in hospitalized cancer patients with VTE.

Estimated annual numbers of US acute‐care hospital patients at risk for venous thromboembolism

Venous thromboembolism (VTE) is a major US health problem. However, the total number of US inpatients who are at risk for VTE is unknown. Our objective was to estimate the number of US acute-care hospital inpatients who were at risk for VTE according to criteria established by the Seventh American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic and Thrombolytic Therapy guidelines for VTE prevention. Using the 2003 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP), patient diagnoses and procedures were examined to identify major surgery patients (age > or = 18 years, length of hospital stay > or = 2 days) and medical patients (age > or = 40 years, length of hospital stay > or = 2 days). ACCP guidelines were used to estimate the number of surgical and medical patients at risk of developing VTE. Of an estimated 38,220,659 discharges in 2003, 7,786,390 (20%) were surgical inpatients; 44% of which were at low risk for VTE, while 15%, 24%, and 17% were at moderate, high, and very high risk for VTE, respectively. Of the remaining 15,161,586 medical patients, 7,742,419 (51%) met ACCP VTE risk criteria. Over 12 million patients, comprising 31% of US hospital discharges in 2003, were at risk of VTE. Given the existence of internationally-accepted evidence-based guidelines for prevention of VTE, research is required to establish if this patient population is receiving recommended VTE prophylaxis.

Hospitals’ compliance with prophylaxis guidelines for venous thromboembolism

A study was conducted to evaluate compliance with the Sixth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy guidelines for the prevention of venous thromboembolism (VTE) in hospitals. Using the HealthFacts database, hospitalized patients, age 40 years or more, with medical conditions at risk for VTE (surgical, trauma, and acute spinal injury patients) were identified. Hospital admissions on or after January 1, 2001, and concluded by March 31, 2005, were included if they met any of the following conditions as defined in the ACCP Consensus Conference on Antithrombotic Therapy guidelines: patients at risk of VTE medical conditions, major orthopedic surgery, general surgery, gynecological surgery, urologic surgery, trauma, neurosurgery, and acute spinal cord injury. Hospitalizations were identified using the International Classification of Diseases, 9th Revision, Clinical Modification codes. The primary objective was to examine whether patients received one of the indicated anticoagulants at the proper dosage and during the relevant hospital days as determined in the ACCP guidelines. Rates of compliance were assessed, and the reasons for guideline noncompliance were also determined. The overall compliance rate with ACCP guidelines was 13.3% (ranging from 2.8% for neurosurgery to 52.4% for orthopedic surgery) in the 123,304 hospital admissions that were reviewed. Only 15.3% of patients with at-risk medical conditions received prophylaxis in accordance with ACCP guidelines. Potential reasons for guideline noncompliance among selected conditions included the omission of prophylaxis, inadequate prophylaxis duration, and the wrong type of anticoagulant. A retrospective study found low rates of compliance with guidelines for thromboprophylaxis.

Duration of Treatment of Deep Vein Thrombosis: Time for a New Approach?

The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy recommends that patients with initial idiopathic deep vein thrombosis (DVT) receive treatment for at least 6-12 months. However, controversy exists as to what treatment duration and intensity are optimal. Some investigators have suggested that it may be feasible to identify patients who are at low risk and those who are at high risk of recurrent venous thromboembolism. If patients can be stratified according to risk, then it might be safe and effective to withdraw oral anticoagulation therapy in those at low risk of recurrence and continue the therapy in those at high risk. Parameters that have been used to attempt to stratify patients with idiopathic DVT according to risk are D-dimer levels, resolution of thrombosis on ultrasound, and sex.

ASHP Therapeutic Position Statement on the Daily Use of Aspirin for Preventing Cardiovascular Events

The effectiveness of aspirin as an antiplatelet agent in preventing cardiovascular events and the progression of coronary heart disease (CHD) has been demonstrated in clinical trials in various patient groups. However, despite adequate evidence of benefit, many eligible patients are not treated with aspirin.1,–3 Using aspirin for the prevention of cardiovascular events is considered a quality marker by the Centers for Medicare and Medicaid Services, the National Quality Forum, and the Joint Commission on Accreditation of Healthcare Organizations. ASHP supports the daily use of aspirin as an adjunct to other effective drug therapies and modifying controllable risk factors for CHD for the following indications: (1) primary prevention of cardiovascular events in adults with increased CHD risk (10-year risk of at least 6% based on Framingham risk scoring)4,–6 and (2) secondary prevention of cardiovascular events in patients with a history of chronic stable angina7 or acute coronary syndromes (unstable angina, non-ST-segment elevation myocardial infarction [MI], and ST-segment elevation MI.)8–10 The Framingham risk scoring system is a simple means of individualizing risk assessments and provides an estimate of total CHD risk over the course of 10 years.11 These positions are consistent with recommendations by the American College of Cardiology and American Heart Association (ACC–AHA),6,–10 the U.S. Preventive Services Task Force,4 the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy,12 and the American Diabetes Association (Table 11).13

The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines

Since the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and previously existing recommendations and review several important changes that we have made in our guideline development process. We made a conscious effort to increase the participation of female authors and of contributors from outside North America, with the latter reflecting the widespread use and dissemination of these guidelines internationally. The change in the title from a conference emphasizing consensus to "ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines" reflects the evidence-based approach to making recommendations. The recommendations follow the grading system described in the 2001 recommendations. If the guideline developers are very certain that benefits do, or do not, outweigh risks, burdens, and costs, they will make a strong recommendation (in our formulation, Grade 1). If they are less certain of the magnitude of the benefits and the risks, burdens, and costs, and thus of their relative impact, they make a weaker Grade 2 recommendation. Consistent results from RCTs generate Grade A recommendations, observational studies with very strong effects or secure generalizations from randomized clinical trials (RCTs) generate Grade C+ recommendations, inconsistent results from RCTs generate Grade B recommendations, and observational studies generate Grade C recommendations. We now use the language "we recommend" for strong recommendations (ie, Grades 1A, 1C+, 1B, and 1C) and "we suggest" for weaker recommendations (ie, Grades 2A, 2C+, 2B, and 2C). While evidence on which recommendation are made remains weak in the fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

Superiority of Fondaparinux Over Enoxaparin in Preventing Venous Thromboembolism in Major Orthopedic Surgery Using Different Efficacy End Points

To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. Patients were randomized to receive either subcutaneous fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. Using the original end point of the fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the fondaparinux group, with a common odds reduction of 55.2% (p = 10(-17); 95% confidence interval, 45.8% to 63.1%) in favor of fondaparinux. The respective incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used.

LMWH for Perioperative Anticoagulation in Patients on Chronic Warfarin Therapy

To review current data regarding low-molecular-weight heparin (LMWH) use for perioperative anticoagulation in patients receiving chronic warfarin therapy. Data were obtained from the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy guidelines and a MEDLINE search (1996-January 2003). Search terms included heparin, low-molecular-weight heparin, warfarin, perioperative care, and anticoagulants. Heparin is the most common agent used as bridge therapy for perioperative anticoagulation in patients on chronic warfarin therapy; LMWHs are also used. Studies that evaluated enoxaparin and/or dalteparin were reviewed. Although published studies demonstrate efficacy and safety of LMWHs, more data are needed to support their use as bridge therapy.

The prevention of venous thromboembolism in older adults: guidelines.

The rationale for thromboprophylaxis is based on the high prevalence of venous thromboembolism (VTE), a disorder involving deep vein thrombosis (DVT) and pulmonary embolism (PE), among hospitalized patients, the clinically silent nature of VTE in most patients, and the morbidity, cost, and potential mortality associated with unprevented thromboembolism. Both DVT and PE cause few specific symptoms, and the clinical diagnosis is unreliable. Since the first clinical manifestation of VTE may be fatal PE, it is inappropriate to wait for symptoms before treatment. Unrecognized and untreated DVT may also cause the postphlebitic syndrome and predispose patients to subsequent episodes of recurrent VTE. Routine screening for VTE has also not been shown to reduce the incidence of symptomatic VTE or fatal PE. Use of effective methods of prophylaxis is more cost effective and is safer than selective, intensive screening for VTE. This article reviews current recommendations for the prevention of VTE as they apply to older adults. The recommendations discussed are based on the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy reported in Chest. 2001;119:132S-175S.

The management of venous thromboembolic disease in older adults.

The incidence and prevalence of venous thromboembolic disease (VTED) increase progressively with age. Although the clinical features, diagnosis, and treatment of VTED are generally similar in older and younger adults, prevalent comorbidities often complicate the management of VTED in the elderly. The Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy provides comprehensive recommendations for the management of VTED. This article summarizes these recommendations as they apply to older adults and highlights factors that may modulate the diagnosis and treatment of VTED in the elderly patient.

Clinical practice guidelines. Managing oral anticoagulant therapy.

Clinical practice guidelines (CPG) provide recommendations based on the summary of large volumes of literature and expert opinion. They are not absolute care directives, but are intended to facilitate individualized decision making related to patient care situations. Each month this column reviews a CPG of direct relevance to clinical practice. Readers are urged to contact the author, Mary Jo Goolsby (mjgoolsby@aanp.org) with requests for reviews of specific clinical guidelines or submissions of manuscripts addressing major guidelines that readers have found helpful in their practice. The Clinical Practice Guideline column is designed to inform practitioners of the wide range of accessible and current recommendations on a myriad of clinical topics. The guideline reviewed this month is actually one part of a large report stemming from the Sixth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy. The management of oral anticoagulant therapy is but one portion of the overall report, complemented and supported by other components, including a preceding chapter that summarizes the mechanisms of action, clinical effectiveness, and therapeutic range of oral agents. This CPG focuses on following issues: (a) initiating and maintaining dosage, (b) managing non-therapeutic dosages, (c) managing the agents during invasive procedures, and (d) recognizing and responding to adverse events. Special situations are discussed, including management of patients who are elderly or pregnant, and comparisons of the management in different models of care. There is in-depth discussion of the literature, accompanied by a summary of recommendations.

Venous Thrombosis and the Pharmacist

The prevention and management of venous thromboembolism have become increasingly important clinical issues that cross many professional and subspecialty boundaries. Better identification of risk factors, improvements in the diagnosis and treatment of thromboembolic disorders, and greatly expanded knowledge related to thromboprophylaxis have presented new challenges for the delivery of evidencebased care. Accumulating data and subsequent recommendations in this area are collected every 3 years in the American College of Chest Physicians Consensus Conference on Antithrombotic Therapy and published as a supplement to the journal Chest, 1 an issue that is widely read by interested hospital pharmacists and physicians. There are many centres of excellence in clinical thromboembolism in North America, all of which are clustered at tertiary care teaching hospitals. At the vast majority of community hospitals, thrombosis prevention and management are not the responsibility of any one practitioner but rest mainly in the hands of physicians in a variety of specialties including hematology, cardiology, internal medicine, orthopedics, and vascular surgery. Most long-term anticoagulation for ambulatory patients is managed by family physicians. Yet we believe that pharmacists are well suited to take on responsibilities in this area, and our purpose in writing this editorial is to try to expedite this transfer of responsibility from physician to pharmacist. Recent studies and surveys have shown that the application of evidence-based practice in several aspects of management of venous thromboembolism could be significantly improved. For example, thromboprophylaxis is frequently underutilized both in general medical inpatients and after high-risk abdominal surgery, whereas the reversal of warfarin overanticoagulation

A Review of Warfarin Dosing and Monitoring

The goal of anticoagulant therapy with warfarin is to administer the lowest effective dose of the drug to maintain the target international normalized ratio (INR). Warfarin, a vitamin K antagonist, is an oral anticoagulant indicated for the prevention and treatment of venous thrombosis and its extension and the prevention and treatment of the thromboembolic complications associated with atrial fibrillation. Warfarin has also been used to prevent recurrent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction, but data supporting these indications are inconclusive at this time (1). Warfarin inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S (2). The anticoagulant and antithrombotic activity of warfarin depends on the clearance of functional clotting factors from the systemic circulation once the drug is administered (2, 3). The earliest changes in INR are typically seen 24 to 36 hours after administration of the dose. The antithrombotic effect of warfarin is not present until approximately the fifth day of therapy, which is dependent on the clearance of prothrombin (1, 2). Initiation of warfarin therapy is challenging, since the pharmacodynamic response is delayed and difficult to predict. Because prothrombin has a half-life of around 50 hours, loading doses of warfarin are of limited value (4). In clinical practice, loading doses (e.g., 7.5 mg or more per day) of warfarin may increase the patient's risk of bleeding complications early in therapy by eliminating the production of functional factor VII (2, 5). Administration of loading doses may place a patient in a hypercoagulable state due to a severe depletion of protein C (2). The administration of a loading dose is a possible source of prolonged hospitalization secondary to dramatic rises in the INR value that may necessitate the administration of vitamin K (5). If a rapid anticoagulant effect is required, an initial dose of heparin or a low molecular-weight heparin should be used and overlapped with warfarin for approximately 4 to 5 days. Once the INR is therapeutic for at least 2 days, the supplemental anticoagulation treatment may be discontinued (1, 4, 5). The safety and efficacy of warfarin therapy are dependent on maintaining the INR within the target range for the indication (Table ​(Table11). When a patient is started on an oral anticoagulant, INR monitoring should be performed daily until the INR is within the therapeutic range for at least 2 consecutive days. Unexpected fluctuations in the INR in an otherwise stable patient could be due to a change in diet, poor compliance, undisclosed drug use, alcohol consumption, or self-medication (2). Lab error should also be considered for unexpected values. Table 1 Recommended therapeutic range for oral anticoagulant therapy* One of the major risks of warfarin therapy is bleeding, which correlates well with INR values. The Fifth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy has published guidelines on the management of patients with high INR values with or without bleeding (Table ​(Table22). Table 2 Management of supratherapeutic INR values*

Quality Improvement Efforts in the Intensive Care Unit: Development of a New Heparin Protocol

ContextAn ongoing process of identifying and implementing breakthrough projects to quickly improve patient outcomes and reduce costs in the intensive care unit.ObjectiveTo develop and test a new protocol for heparin administration in the intensive care unit, replacing the 5 existing protocols and ensuring compliance with the recommendations of the Fifth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy.DesignA pilot study comparing results of 58 patients on the 5 existing protocols with those of 10 patients on the new heparin protocol. Setting: Baylor University Medical Center, a large tertiary hospital in Dallas, Texas, with 115 adult intensive care unit beds.InterventionsHeparin dosing was based on a patient's weight, and anticoagulation was monitored through the heparin assay. Main outcome measures: In the control group treated according to the existing protocols, 5 patients (8.6%) received optimal bolus doses, and 2 patients (3.4%) received optimal infusion doses. In the pilot group treated according to the new protocols, 9 patients (90%) received optimal bolus doses, and all received optimal infusion doses. Results: The implementation of the new heparin protocol resulted in better patient care, improved nursing efficiency, and reduced costs. Conclusions: As shown in this example, a rapid breakthrough project following a plan-do-study-act cycle can apply best practices relatively quickly and lead to better patient outcomes.

New developments in the prevention and treatment of venous thromboembolism.

Although unfractionated heparin has been widely used for preventing and treating venous thromboembolism, low-molecular-weight heparins (LMWHs) have been extensively studied. In particular, LMWHs have been valuable in the prevention of venous thromboembolism in high-risk surgical patients, such as those undergoing total joint replacement, and in high-risk medical patients. Recent studies indicated that the extended use of LMWHs after discharge in patients undergoing total hip replacement significantly decreases the frequency of venous thrombosis compared with placebo. Furthermore, LMWHs have been shown to be as effective and safe as unfractionated heparin for the initial treatment of both deep vein thrombosis and pulmonary embolism and have extended the treatment of these conditions into the outpatient setting. New recommendations from the sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy and the rationale for change are discussed.