Biomedical subjects

Henry Bussey

Publications and source records attributed to Henry Bussey.

3 recordsLinked to original sources

PubMed2004

The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. The article describes the antithrombotic effect of VKAs, the monitoring of anticoagulation intensity, the clinical applications of VKA therapy, and the optimal therapeutic range of VKAs, and provides specific management recommendations. Grade 1 recommendations are strong, and indicate that the benefits do, or do not, outweigh the risks, burdens, and costs. Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this article are the following: for dosing of VKAs, we suggest the initiation of oral anticoagulation therapy with doses between 5 and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 2B). In the elderly and in other patient subgroups with an elevated bleeding risk, we suggest a starting dose at < or = 5 mg (Grade 2C). We recommend basing subsequent doses after the initial two or three doses on the results of INR monitoring (Grade 1C). The article also includes several specific recommendations for the management of patients with INRs above the therapeutic range and for patients requiring invasive procedures. For example, in patients with mild to moderately elevated INRs without major bleeding, we suggest that when vitamin K is to be given it be administered orally rather than subcutaneously (Grade 1A). For the management of patients with a low risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before they undergo surgery (Grade 2C). For patients with a high risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before surgery, to allow the INR to return to normal, and beginning therapy with full-dose unfractionated heparin or full-dose low-molecular-weight heparin as the INR falls (Grade 2C). In patients undergoing dental procedures, we suggest the use of tranexamic acid mouthwash (Grade 2B) or epsilon amino caproic acid mouthwash without interrupting anticoagulant therapy (Grade 2B) if there is a concern for local bleeding. For most patients who have a lupus inhibitor, we suggest a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 2B]. In patients with recurrent thromboembolic events with a therapeutic INR or other additional risk factors, we suggest a target INR of 3.0 (range, 2.5 to 3.5) [Grade 2C]. As models of anticoagulation monitoring and management, we recommend that clinicians incorporate patient education, systematic INR testing, tracking, and follow-up, and good communication with patients concerning results and dosing decisions (Grade 1C+).

Administration, Oral↗

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↗

PubMed2002

Traditional anticoagulant therapy: why abandon half a century of success?

The benefits of low-molecular-weight heparins (LMWHs) over heparin and warfarin in treating and preventing thromboembolic disorders are discussed. Numerous advantages are associated with using heparin for treating and preventing thromboembolic disorders. Heparin's short half-life allows for relatively easy and frequent adjustments of therapy. Warfarin has a long half-life and high bioavailability that allow for once-daily administration and a prolonged pharmacodynamic effect. However, approximately 3-5% of patients develop heparin-induced thrombocytopenia with potentially catastrophic complications. Warfarin also has numerous limitations, including frequent and specialized monitoring, an inherent variability in response over time, a propensity for altering the international normalized ratio, and the potential for causing errors in laboratory test values. LMWHs eliminate or reduce the major disadvantages of anticoagulant therapy with heparin and warfarin. The advantages of LMWHs over unfractionated heparins include an improved pharmacokinetic profile. LMWHs are recommended for treating deep vein thrombosis (DVT). They offer convenient administration and the potential for outpatient treatment. They may also result in a slightly lower rate of thromboembolism recurrence and extend the life of cancer patients. For DVT prophylaxis, LMWHs have demonstrated efficacy with 45-70% relative-risk reduction in patients undergoing total hip or total knee replacement and in patients with hip fracture. However, more data are needed for administration to special patient populations, such as the obese and those in renal failure. LMWHs eliminate or reduce the major disadvantages of anticoagulant therapy with heparin and warfarin for treating and preventing thromboembolic disorders. Further study is needed regarding their administration in special populations.

Anticoagulants↗