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      Life-threatening hemorrhage following subcutaneous heparin therapy

      case-report

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          Abstract

          Prophylactic administration of unfractionated heparin is a common practice in a perioperative period. Heparin monitoring with subcutaneous dosing is not recommended; however it becomes important in selected patients. We report a case of massive hemorrhage with subcutaneous heparin administration in an HIV-positive male patient with cachexia and mild liver dysfunction. Prolonged activated plasma thromboplastin time and thrombin time, but normal reptilase time well as response to protamine sulfate point towards the heparin effect. Inhibitor screen was negative and factor VIII activity was normal. All these rule out the possibility of acquired factor VIII inhibitor or any other inhibitor and confirm that this bleeding was due to heparin overdose. We believe that delayed clearance of UH secondary to possible involvement of reticuloendothelial system might have been be responsible for heparin overdose even though inadvertent administration of large dose of heparin intravenously can not be completely ruled out. Administration of unfractionated heparin to a patient with cachexia and abnormal liver function warrants close attention to heparin monitoring or switch to low molecular weight heparin since its mechanism of elimination differs.

          Most cited references10

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          Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents.

          For more than 60 years, heparin and coumarin have been mainstays of anticoagulation therapy. They are widely available, inexpensive, effective, and have specific antidotes but are regarded as problematic because of their need for careful monitoring. In addition, coumarin has a delayed onset of action, interacts with many medications, has a narrow therapeutic window, and is paradoxically prothrombotic in certain settings (ie, can precipitate "coumarin necrosis"). Heparin may require monitoring of its therapeutic effect and can also cause thrombosis (heparin-induced thrombocytopenia/thrombosis syndrome). These limitations have led to the development of new anticoagulants with the potential to replace current agents. These newer agents fall into 2 classes, based on whether they are antithrombin dependent (low-molecular-weight heparin, fondaparinux) or antithrombin independent (direct inhibitors of factor Xa and thrombin [factor IIa]). This paper addresses newer anticoagulants, reviewing their efficacy and limitations, and focuses on the risk of major bleeding that may complicate their use. In contrast to heparin and coumarin, none of these newer agents has a specific antidote that completely reverses its anticoagulant effect. Available data on the efficacy and safety of current and experimental agents for anticoagulant reversal are reviewed, and a plan for management of anticoagulant-induced bleeding is presented.
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            The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977-99.

            Previous studies of the development of inhibitors and their impact on mortality have been small. To examine the development of inhibitors in people with hemophilia in the UK and their effect on subsequent mortality. 6078 males with hemophilia A and 1172 males with hemophilia B registered in the UK Haemophilia Centre Doctors' Organisation database, 1977-98. In severe hemophilia A inhibitors developed at rates of 34.4, 5.2 and 3.8 per 1000 years at ages <5, 5-14 and 15+years; cumulative risks at ages 5 and 75 were 16% and 36%. In hemophilia A the rate of inhibitor development decreased during 1977-90, but increased during the 1990s. In severe hemophilia B inhibitors developed at rates of 13.3 and 0.2 per 1000 years at ages <5 and 5+ and cumulative risks at ages 5 and 75 were 6% and 8%. With HIV, inhibitor development did not increase mortality. In severe hemophilia without HIV, inhibitor development doubled mortality during 1977-92, but during 1993-99 mortality was identical with and without inhibitors. In severe hemophilia without HIV but with inhibitors, mortality from causes involving bleeding decreased during 1977-99 (P = 0.001) as did mortality involving intracranial hemorrhage (P = 0.007). These data provide estimates of the rate of inhibitor development in hemophilia A and hemophilia B, and they show that the rate of inhibitor development has varied over time, although the reasons for this remain unclear. They also show that in severe hemophilia the substantial increase in mortality previously associated with inhibitors is no longer present.
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              Thrombosis and a hypercoagulable state in HIV-infected patients.

              Human immunodeficiency virus infection is an illness with protean manifestations including hematological abnormalities. Thromboembolic complications in HIV-infected patients have been described. Recent literature describes an incidence ranging from 0.26% to 7.6%; higher incidence is seen in patients with active opportunistic infections or malignancy, and in patients with the acquired immunodeficiency syndrome. A variety of potential mechanisms have been proposed to account for the observed hypercoagulability in HIV-infected patients. These include the presence of antiphospholipid-anticardiolipin antibodies, decreased activities of natural anticoagulants (especially protein S), and increased platelet activation. Recent epidemiological studies emphasize the increased incidence of thromboembolic events including myocardial infarction in the HIV-infected population after the introduction of highly active antiretroviral therapy. The use of protease inhibitors in particular is implicated. A hypercoagulable state and especially thromboses are emerging as clinical issues in HIV-infected patients. Further studies are in order to more clearly delineate the pathophysiologic mechanism(s) of thromboses in HIV-infected patients.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2009
                26 March 2009
                : 5
                : 51-54
                Affiliations
                Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
                Author notes
                Correspondence: Daniel Talmor, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, One Deaconess Rd, CC-470, Boston, MA 02215, USA, Tel +1 617 754 3257, Fax +1 617 754 2735, Email dtalmor@ 123456bidmc.harvard.edu
                Article
                tcrm-5-0051
                2697517
                19436612
                3536c9ea-e6fc-4d59-8493-9f1d154745ab
                © 2009 Hudcova and Talmor, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Case Report

                Medicine
                unfractionated heparin,bleeding,prophylaxis,liver dysfunction,cachexia,hiv
                Medicine
                unfractionated heparin, bleeding, prophylaxis, liver dysfunction, cachexia, hiv

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