Overview of heparin-induced thrombocytopeniaSpinler, Sarah, A.;Dager,, William
doi: 10.1093/ajhp/60.suppl_5.S5pmid: 14593977
Abstract A brief overview of the pathophysiology, diagnosis, and treatment of heparin-induced thrombocytopenia (HIT) is discussed. Following any exposure to unfractionated heparin or low-molecular-weight heparin (LMWH), HIT, a serious allergic drug reaction, may occur. The frequency of HIT is thought to range from 1 to 5% of patients receiving heparin. This immune-mediated syndrome is paradoxically associated with thrombosis, not bleeding, with thrombin generation playing a central role. The diagnosis of HIT is based upon clinical findings that can be confirmed with laboratory assay; however, when there is clinical suspicion of HIT, all forms of heparin therapy should be immediately discontinued and initiation of alternative anticoagulation is strongly encouraged. In the presence of HIT, the use of LMWHs or initiation of warfarin without additional effective anticoagulation is not recommended. Argatroban and lepirudin, two direct thrombin inhibitors (DTIs), are approved by the Food and Drug Administration for the management of HIT. Both agents have been studied in the treatment and prevention of thrombotic events associated with HIT. Argatroban, a univalent inhibitor of thrombin, is eliminated via the liver, while lepirudin, the first DTI approved for HIT, is a bivalent thrombin inhibitor that is cleared by the kidneys. Neither argatroban nor lepirudin demonstrates cross-reactivity with heparin-induced antibodies, and both DTIs have been associated with effective anticoagulation and platelet recovery in patients with HIT. The appropriate use of DTIs in HIT reduces the risk of thrombotic events and severe consequences associated with this serious drug reaction. Anticoagulants, Argatroban, Diagnosis, Excretion, Heparin, Lepirudin, Thrombocytopenia, Toxicity This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 11, 2002, during the ASHP Midyear Clinical Meeting in Atlanta, GA, and supported by an unrestricted educational grant from Berlex Laboratories, Inc. Dr. Spinler and Dr. Dager received honorariums for participating in this symposium. Dr. Spinler also serves as a consultant for Berlex Laboratories, Inc. Copyright © 2003 by American Society of Health-System Pharmacists
Direct thrombin inhibitor therapy in the cardiovascular patientChesebro, James, H.
doi: 10.1093/ajhp/60.suppl_5.S19pmid: 14593979
Abstract Direct thrombin inhibitors in cardiovascular patients are discussed. Patients presenting with acute coronary syndromes (ACS) of ST- and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI, respectively) or unstable angina develop mural thrombi within minutes of plaque disruption or erosion. Initial acute therapy includes heparin and aspirin. Up to 60% of patients have coronary revascularization to reduce the high risk of death, new myocardial infarction (MI), or recurrent angina. In addition, heparin may initiate a serious allergic, prothrombotic drug reaction, heparin-induced thrombocytopenia (HIT), in 1-5% of patients. Acute cessation of heparin and initiation of direct thrombin inhibitor (DTI) therapy for suspected HIT are vital and well established. Several clinical trials comparing DTIs with heparin have been done in ACS and percutaneous coronary intervention (PCI), and have shown excellent potency in inhibiting thrombus formation and reducing coronary events. An overview of results from published studies evaluating the use of bivalent and univalent DTIs in the cardiovascular patient is presented. Four DTIs are discussed: two r-hirudins (lepirudin and desirudin), both bivalent with stable chain and renal excretion; bivalirudin, bivalent with rapid-chain metabolism; and argatroban, univalent with hepatic metabolism. The extensive clinical experience with r-hirudin in cardiovascular patients suggests that it is an excellent choice for managing patients with HIT and is easy to use in converting to warfarin, since it does not significantly change the prothrombin time. Angioplasty, Anticoagulants, Argatroban, Bivalirudin, Cardiovascular diseases, Desirudin, Excretion, Heparin, Lepirudin, Prothrombin time, Thrombocytopenia, Toxicity This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 11, 2002, during the ASHP Midyear Clinical Meeting in Atlanta, GA, and supported by an unrestricted educational grant from Berlex Laboratories, Inc. Dr. Chesebro received an honorarium for participating in this symposium and has also received research grant funding from Berlex Laboratories, Inc., for an investigator-initiated protocol. Copyright © 2003 by American Society of Health-System Pharmacists
Clinical utility of subcutaneous hirudinsDeitcher, Steven, R.
doi: 10.1093/ajhp/60.suppl_5.S27pmid: 14593980
Abstract The clinical utility of subcutaneous hirudins is discussed. The term "hirudins" refers to a class of antithrombotic agents structurally derived from the medicinal leech salivary protein hirudin. Breakthroughs in biotechnology over the past 20 years have resulted in the development of recombinant versions of hirudin (r-hirudin). Lepirudin is one such r-hirudin that is identical to natural hirudin except for the substitution of leucine for isoleucine at the N-terminus and the elimination of a sulfate group on the tyrosine at position 63. Another r-hirudin, desirudin, is identical to hirudin except for a valine-valine in the N-terminus and the absence of the sulfate group on tyrosine at position 63. Both r-hirudins are bivalent and tightly bind to both the catalytic site and the exposite of thrombin to exert their inhibitory effects on thrombin. Unfractionated heparin (UF) and low-molecular-weight heparins (LMWHs) are widely used in medical and surgical patients to prevent and treat arterial and venous thrombotic events. Besides bleeding, the major adverse effect of heparins is heparin-induced thrombocytopenia (HIT). HIT is associated with a paradoxical hypercoagulable state and marked risk of clinical thrombosis. Management of HIT requires the immediate cessation of all heparin exposure, and the initiation of an alternative anticoagulant. Because r-hirudins are effective agents and do not cross-react with HIT-associated antibodies, they are excellent anticoagulants in patients with past or current HIT. Clinical trials have also demonstrated the efficacy and safety of subcutaneous (s.c.) r-hirudins compared to heparins in non-HIT settings. Results of these trials support the use of r-hirudin therapy in patients with HIT or at risk of developing HIT. Additionally, case reports have described safe and effective use of s.c. r-hirudin therapy in the outpatient setting in both HIT and non-HIT patients. Anticoagulants, Desirudin, Heparin, Lepirudin, Thrombocytopenia, Toxicity This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 11, 2002, during the ASHP Midyear Clinical Meeting in Atlanta, GA, and supported by an unrestricted educational grant from Berlex Laboratories, Inc. Dr. Deitcher received an honorarium for participating in this symposium. Copyright © 2003 by American Society of Health-System Pharmacists
Treatment options for heparin-induced thrombocytopeniaGreinacher,, Andreas
doi: 10.1093/ajhp/60.suppl_5.S12pmid: 14593978
Abstract Appropriate management, as well as efficacy and safety, of heparin-induced thrombocytopenia (HIT) and prevention of severe consequences with argatroban and lepirudin are discussed. Heparin-induced thrombocytopenia, a serious immune-mediated drug reaction, can occur as an isolated incident (isolated HIT) or with acute thrombosis sometimes referred to as HIT and associated thrombosis syndrome (HITTS). Due to the severe consequences associated with HIT, appropriate management is critical. Argatroban and lepirudin, two direct thrombin inhibitors (DTIs), are currently FDA approved for use in patients with HIT. The clinical experience with these agents is critically examined in this article. The safety and efficacy of argatroban in management of HIT were the subject of a single published clinical trial. The study was designed to reflect conventional clinical practice, whereby treatment of patients with HIT was initiated upon clinical suspicion. In several of these patients, HIT antibodies could not be demonstrated. Compared to historical controls, argatroban demonstrated efficacy in patients with isolated HIT; however, no differences were observed in HIT patients with acute thrombosis. Rates of bleeding episodes did not differ between argatroban and control. The clinical efficacy and safety of lepirudin have been the subject of three clinical trials and one large drug monitoring program. Lepirudin has demonstrated benefit in HIT patients with or without existing thromboembolism. Bleeding rates were higher than in the historical control. However, bleedings requiring transfusion did not differ. Although no direct head-to-head comparison trials of argatroban and lepirudin have been conducted, parallels can be drawn between the agents based on careful review of published clinical trials. Consistently, rates of new thrombosis, limb amputation, and death appear to be lower in patients treated with lepirudin as compared with those treated with argatroban, whereas the risk for major bleeding per patient day seems to be similar with both DTIs. Anticoagulants, Argatroban, Heparin, Lepirudin, Thrombocytopenia, Toxicity This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 11, 2002, during the ASHP Midyear Clinical Meeting in Atlanta, GA, and supported by an unrestricted educational grant from Berlex Laboratories, Inc. Dr. Greinacher received an honorarium for participating in this symposium. Dr. Greinacher also serves as a consultant for Berlex Laboratories, Inc.; Celltech Pharmaceuticals, Inc.; and Pharmion Corporation and has also participated as an advisor to Mitsubishi Corporation. Copyright © 2003 by American Society of Health-System Pharmacists