Biomedical subjects

Heparin Consensus Group

Publications and source records attributed to Heparin Consensus Group.

9 recordsLinked to original sources

PubMed2004

Heparin overview and issues.

Unfractionated heparin (UFH), which has been available commercially for over half a century, has been the most widely used agent for quickly suppressing thrombosis. When given intravenously, UFH quickly binds to and activates antithrombin, which then inhibits several activated factors in the clotting cascade. For decades, UFH was invaluable for treating arterial and venous thrombosis, and no alternative was available. The short half-life of UFH and the fact that its action could be reversed readily with protamine made it an almost ideal antithrombotic agent. However, variable pharmacokinetics, together with problems of inaccuracy and unreliability of the activated partial thromboplastin time, have made it difficult to use this drug optimally. In addition, side effects such as osteoporosis, heparin-induced thrombocytopenia (HIT), and delayed HIT have led to increased concerns about the use of UFH in view of the advantages offered by newer agents. Fractionating heparin into low-molecular-weight heparins that still retain the pentasaccharide active site provided a way to achieve the same type of therapeutic effect with more predictable dosing and fewer adverse effects. Similarly, a pentasaccharide has been synthesized and marketed as fondaparinux. Although these advances have improved our therapeutic options, continued advances on the horizon raise the question of whether the use of UFH will soon be abandoned.

Drug Monitoring↗

PubMed2004

Challenges in variation and responsiveness of unfractionated heparin.

Unfractionated heparin (UFH) has been in clinical use for more than half a century. Despite its undoubted contribution to the treatment and prevention of thrombosis, heparin is significantly limited by its variable biochemical composition and unpredictable pharmacokinetics. The situation is compounded by the fact that methods for monitoring heparin do not necessarily reflect its therapeutic effect. The activated partial thromboplastin time (aPTT) is a method for monitoring heparin therapy that is simple, cheap, and readily available. However, it is also poorly standardized and is affected by numerous factors-both analytic and preanalytic-that are unrelated to the heparin effect. Establishing an appropriate therapeutic range for the aPTT is challenging for smaller clinical laboratories, and the antifactor Xa method of measuring heparin levels is not widely available. The College of American Pathologists published consensus guidelines in an effort to improve the laboratory monitoring of UFH therapy. However, it seems unlikely that the laboratory problems associated with monitoring UFH will be resolved. Unfractionated heparin is highly antigenic and carries a significant risk of heparin-induced thrombocytopenia (HIT). Even in the absence of thrombocytopenia or thrombosis, the presence of heparin-associated antibodies may predict adverse clinical outcomes and strengthen the rationale for the ultimate replacement of UFH. Fortunately, alternatives to UFH, such as low-molecular-weight heparins, direct thrombin inhibitors, and more specific factor Xa inhibitors, are becoming available for clinical use. The pharmacokinetics of these agents are more predictable and rely much less on laboratory monitoring. Nonheparin agents also eliminate the risk of HIT. The emergence of these newer anticoagulants makes the continued use of UFH increasingly difficult to justify.

Antithrombins↗

PubMed2004

Anticoagulant prophylaxis in medical patients: an objective assessment.

Venous thromboembolism (VTE) is a clinically silent and potentially fatal disease that manifests as deep vein thrombosis (DVT) and pulmonary embolism. Venous thromboembolism remains a serious public health challenge, with an ever-increasing odds ratio of occurrence given the aging population in the United States. This article reviews the epidemiology of VTE; risk factor identification and stratification as a means of advancing awareness, prevention, and detection of VTE; and prophylaxis options and their outcomes, particularly administration of unfractionated heparin (UFH) 5000 U subcutaneously every 12 versus 8 hours in the at-risk medical patient population. The important studies comparing outcomes of these different UFH dosing regimens compared with placebo and low-molecular-weight heparins also are discussed. Consensus recommendations shaping contemporary clinical practice guidelines in this setting are highlighted. A systemwide approach to treatment of all medical patients who are risk stratified and receiving appropriate pharmacologic prophylaxis is recommended.

Fibrinolytic Agents↗

PubMed2004

Treatment of venous thromboembolism: challenging the unfractionated heparin standard.

Venous thromboembolism (VTE) is a major public health problem leading to high morbidity and mortality in the United States. Since more then 50% of patients with VTE may have asymptomatic disease, the start of appropriate therapy often is delayed. Traditionally, intravenous unfractionated heparin (UFH) has been used to manage the acute phase of VTE. Although an effective agent, numerous limitations are associated with the use of UFH therapy, such as the need for careful monitoring and frequent dosing adjustments. In addition, the assay used to monitor UFH--the activated partial thromboplastin time (aPTT)--does not correlate reliably with plasma heparin levels or antithrombotic activity. In the early 1990s, the low-molecular-weight heparins (LMWHs) emerged as alternative anticoagulants to UFH and began to successfully challenge the UFH standard for treatment of VTE. Clinical evidence has consistently demonstrated that LMWHs given subcutaneously are at least as safe and as effective, if not better, than intravenous UFH. This anticoagulant class has a much more predictable dose-response relationship, requires little or no monitoring, and provides cost-saving opportunities for outpatient management of VTE. The LMWHs are now considered the treatment of choice for many patients with VTE and are largely replacing UFH for this indication. In the last decade, additional agents, such as direct thrombin inhibitors and factor Xa inhibitors, have emerged as potential future alternatives for treatment of VTE. As clinical data regarding these new agents for treatment of VTE continue to evolve, their role in clinical practice will be elucidated.

Clinical Trials as Topic↗

PubMed2004

Unfractionated heparin in cardiology: redefining the standard of practice.

Acute coronary syndromes (ACS) consist of unstable angina (UA), non-ST-segment myocardial infarction (NSTEMI) and ST-segment myocardial infarction (STEMI). Timely intervention with effective, predictable antithrombin therapy is critically important in the early management of these conditions. Platelet aggregation is also an important component of thrombus formation in arterial thrombosis. Historically, unfractionated heparin (UFH) has been combined with aspirin to suppress thrombin propagation and fibrin formation; however, its effectiveness has been questioned in this setting. Unlike newer anticoagulant alternatives, UFH paradoxically stimulates platelet aggregation, which may further promote clot formation. In addition, obtaining a valid therapeutic activated partial thromboplastin time (aPTT) in cardiology patients is a major challenge, and dosing is complex. Due to substantial variation in reagents and instruments, target aPTT ranges for UFH in ACS clinical trials cannot be extrapolated to individual institutions. Further, the risk of ischemic events is greater shortly after abrupt discontinuation of UFH compared with alternative agents with longer half-lives and less stimulation of platelet aggregation. Key UA-NSTEMI clinical trials have demonstrated that UFH is inferior to newer agents, such as the low-molecular-weight heparins (LMWHs). Consistent with this evidence, the most recent practice guidelines of the American College of Cardiology and the American Heart Association in UA-NSTEMI identify the LMWH enoxaparin as the agent of choice. In patients with STEMI receiving the fibrinolytic tenecteplase as reperfusion therapy, enoxaparin has also been superior to UFH in combination. In percutaneous procedures, newer indirect (enoxaparin) and direct (bivalirudin) antithrombins have demonstrated safety and efficacy. There is little doubt that as we move forward in optimizing adjunctive anticoagulation in the cardiology setting, UFH will largely be replaced by better antithrombin agents.

Angioplasty, Balloon↗

PubMed2004

Unfractionated heparin dosing nomograms: road maps to where?

Weight-adjusted nomograms have been a significant advance in the use of unfractionated heparin (UFH). Clinical trials have demonstrated the ability of weight-adjusted nomograms to achieve a therapeutic activated partial thromboplastin time (aPTT) more rapidly than with standard UFH dosing. Despite this advantage, a significant number of patients have subtherapeutic and supratherapeutic aPTTs. Real-world experiences also corroborate the inability to keep UFH therapeutic with the use of nomograms. Despite the limitations of UFH nomograms, they have been used in several different types of venous and arterial thrombosis treatment settings. Unfortunately, these nomograms are not all consistent and require a considerable amount of time for training health care professionals on their use in order to limit the potential for medication errors. Although UFH nomograms have provided advancement over standard UFH dosing, their limitations still generate the desire for a more predictable anticoagulant.

Body Weight↗

PubMed2004

Unfractionated heparin: focus on a high-alert drug.

Unfractionated heparin (UFH) is associated with a high rate of drug-related problems due to either its inherent pharmacologic properties or an extension of these properties often caused by medication errors. The drug-related problems associated with UFH can significantly hinder the success of therapy and negatively affect the overall cost of care. Unfractionated heparin has been classified as a high-alert drug by the Institute for Safe Medication Practices. Approximately 2.1% of the total records submitted to the MedMARx national error database were related to UFH; 4.5-5.5% of these errors reported were harmful. With this high potential for error, it is essential that all health care providers adopt a collaborative or systems approach to identify solutions to reduce the occurrence of these medication errors. The Joint Commission on Accreditation of Healthcare Organizations has published national patient safety goals for improving the safety of patient care, many of which are applicable to UFH therapy. Unfractionated heparin drug-related problems not necessarily related to medication errors include heparin-induced thrombocytopenia, bleeding events, and osteopenia. Heparin-induced thrombocytopenia is a serious complication of heparin therapy and remains seriously undiagnosed. Bleeding events often occur with therapeutic as well as prophylactic UFH administration even when monitoring indexes are within the therapeutic range. However, due to the variability associated with UFH monitoring methods, definitive guidelines are lacking to assist in avoiding such serious events. Osteopenia has been associated with long-term UFH therapy; one third of patients experience reductions in bone density, potentially leading to fractures. Today, safer alternative anticoagulation therapies are available, such as the low-molecular-weight heparins. When compared with UFH, these alternative therapies provide equivalent or superior efficacy for numerous indications.

Bone Diseases, Metabolic↗

PubMed2004

Unfractionated heparin: a nursing dilemma.

Nurses face challenges in all aspects of their practice, especially with administering and monitoring drugs in a safe, effective manner. Key factors known to affect drug administration include general drug knowledge, formal nurse education, continuing education needs, clinical experience, and the nationwide nursing shortage. Other factors are advances in technologic aids and quality improvement initiatives. Emphasis on patient safety is growing, especially as it relates to drug therapy and high-alert drugs such as unfractionated heparin (UFH). Specific interventions related to UFH administration can enhance patient care management. Because nurses are at the site of direct patient care, they are often in an opportune position for identifying medication errors. At the same time, and most important, nurses need to collaborate with other health care professionals to actively develop solutions to minimize these errors. Adopting a systems approach and working collaboratively with an interdisciplinary team can result in improved patient outcomes.

Education, Nursing↗

PubMed2004

Economics of unfractionated heparin: beyond acquisition cost.

Despite numerous clinical trials demonstrating advantages of new anticoagulants, unfractionated heparin (UFH) is still used by a number of clinicians in the United States. The reason for this continued use of UFH is not superior efficacy, improved safety, or convenience, but low acquisition cost. However, several other costs associated with the use of UFH are often not considered. Appropriate economic analysis, which considers both cost and outcomes, has not demonstrated support for continued use of UFH. Its continued use based simply on lower cost is not justified by the literature.

Fibrinolytic Agents↗