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A case series of five episodes of massive LMWH non-fatal self-induced overdose in a single patient

2012; Elsevier BV; Volume: 129; Issue: 5 Linguagem: Inglês

10.1016/j.thromres.2011.12.033

1879-2472

Jacob Odeberg, Anders Carlsson, Caroline Hällsjö-Sander, Anna Ågren,

Heparin-Induced Thrombocytopenia and Thrombosis

Low molecular weight heparins (LMWH) are frequently used for the prophylaxis and treatment of venous thromboembolic diseases (VTE). Their subcutaneous administration in fixed doses has made possible the treatment of thromboembolic diseases in outpatient settings. Self-induced massive overdoses have recently been described in case reports, with various treatments and outcomes [ 1 Monte A.A. Bodmer M. Schaeffer T.H. Low-molecular-weight heparin overdose: management by observation. Ann Pharmacother. 2010; 44: 1836-1839 Crossref PubMed Scopus (15) Google Scholar , 2 Hasan K. Lazo-Langner A. Acedillo R. Zeller M. Hackam D.G. Anticoagulant response after dalteparin overdose. J Thromb Haemost. 2010; 8: 2321-2323 Crossref PubMed Scopus (5) Google Scholar , 3 Bjornaas M.A. Jacobsen E.M. Jacobsen D. Nonfatal self-poisoning with LMW heparin and the use of antidote. Thromb Res. 2010; 126: e403-e405 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. Thus, the management of such episodes is not clarified. Protamine is recommended by the American College of Chest Physicians for the reversal of LMWH in about the same doses that is established for reversal of the effect of heparin (unfractioned heparin, UFH)[ [4] Hirsh J. Bauer K.A. Donati M.B. Gould M. Samama M.M. Weitz J.I. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133: 141S-159S Crossref PubMed Scopus (629) Google Scholar ]. However, in contrast to heparin, LMWH is only partly neutralized by protamine [ [5] Summary of Product Characteristics (SPC) protamine sulphate (LEO Pharma). Medical Product Agency, 2010www.mpa.se Google Scholar ]. Furthermore, in massive overdose, the amounts of protamine needed to neutralize LMWH would far exceed 50 mg, which is the maximal single dose recommended [ [5] Summary of Product Characteristics (SPC) protamine sulphate (LEO Pharma). Medical Product Agency, 2010www.mpa.se Google Scholar ]. In a recent case report on an overdose of 212,500 IU of the LMWH dalteparin a bolus dose of 500 mg reversed the LMWH effect only partially and transiently (measured as normalized APTT and anti-Xa) [ [3] Bjornaas M.A. Jacobsen E.M. Jacobsen D. Nonfatal self-poisoning with LMW heparin and the use of antidote. Thromb Res. 2010; 126: e403-e405 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. However, no bleeding complication was noted, in accordance with other reports [ 1 Monte A.A. Bodmer M. Schaeffer T.H. Low-molecular-weight heparin overdose: management by observation. Ann Pharmacother. 2010; 44: 1836-1839 Crossref PubMed Scopus (15) Google Scholar , 2 Hasan K. Lazo-Langner A. Acedillo R. Zeller M. Hackam D.G. Anticoagulant response after dalteparin overdose. J Thromb Haemost. 2010; 8: 2321-2323 Crossref PubMed Scopus (5) Google Scholar ]. This may indicate that a conservative approach in the management of LMWH overdose might be appropriate in patients without symptoms. Such an approach is supported by our present report describing very large overdoses of dalteparin in a single patient. However, our report also demonstrates that the presence of trauma or a locus minoris for bleeding should warrant a more active management.