Contemporary Use of and Future Roles for Heparin in Antithrombotic Therapy

Abstract

Although heparin therapy is an established component of the prevention and treatment of thromboembolic disease, recent advances have resulted in improvements in the clinical use of this agent. Studies have shown that weight-based dosing influences significantly both the time to reach a therapeutic intensity of anticoagulation and the incidence of thromboembolic recurrence. It is now considered the standard of care. A growing understanding of the variability among activated partial thromboplastin time (aPTT) reagents and the influence of these differences on aPTT outcomes has led to the use of reagent-specific therapeutic ranges for heparin monitoring. Many practitioners now choose to adjust the therapeutic range to correspond to heparin serum concentrations of 0.2-0.4 U/mL rather than the more common practice of prolonging aPTT to 1.5-2.5 times the mean normal aPTT. Pharmaceutical companies have developed low molecular weight heparins to minimize adverse effects associated with unfractionated heparin. More specific thrombin inhibitors are also under investigation with the aim of improving clinical outcomes in coronary syndromes now treated with heparin. Low molecular weight heparins or specific thrombin inhibitors are unlikely to replace unfractionated heparin in the near future. Therefore, optimum dosing and appropriate monitoring of heparin are critically important in the management of thromboembolic disease.

Evaluation of a bedside device to assess the activated partial thromboplastin time for heparin monitoring in infants

“…The type of measurement system, handling of blood samples and composition of the reagent, are examples of factors that affect aPTT analysis [21]. The difference in heparin sensitivity between methods is a potential confounding factor in any comparative study of aPTT monitoring techniques.…”

Treatment of Heparin-Induced Thrombocytopenia: Is There a Role for Bivalirudin?

“…2 Many pharmacologic differences exist among the direct thrombin inhibitors (Table 1). 2,4,[6][7][8][9][10] Lepirudin Lepirudin is indicated for anticoagulation in patients with HIT and associated thromboembolic disease in order to prevent thromboembolic complications. 6 Lepirudin is a recombinant form of hirudin, isolated from the leech, and it differs from the natural product by the substitution of leucine for isoleucine at the N-terminal and the deletion of a sulfate group on tyrosine 63.…”

“…6 Lepirudin is a recombinant form of hirudin, isolated from the leech, and it differs from the natural product by the substitution of leucine for isoleucine at the N-terminal and the deletion of a sulfate group on tyrosine 63. 7,8 Lepirudin is a highly specific thrombin inhibitor that exerts its anticoagulant effect by directly complexing with thrombin, which inactivates the center of the enzyme that catalyzes blood clot formation. 7,9 Consequently, neither activation by antiheparin proteins nor direct effects on platelets and endothelial cells are observed with lepirudin, in contrast to UFH.…”

“…7,9 Consequently, neither activation by antiheparin proteins nor direct effects on platelets and endothelial cells are observed with lepirudin, in contrast to UFH. 8…”

Heparin-Induced Thrombocytopenia and Thrombosis: A Review of Pharmacologic Therapy

“…Therefore, the advantages of lepirudin over heparin in anticoagulation treatment for patients with Hill are: (1) lepirudin is not inactivated by anti-heparin proteins, (2) lepirudin inactivates both subepithelium-bound thrombin and circulating throm bin, and (3) lepirudin has no direct effects on platelet and endothelial cells. 22,23…”