Heparin-induced skin necrosis at the injection site is a rare adverse effect, more commonly associated with standard heparins than with low-molecular-weight heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH-induced skin necrosis in a female during prophylactic treatment with LMWH after a surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced antibodies was positive. This case describes the occurrence of LMWH-induced skin necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is more frequent than previously suspected.

Introduction: Iron (Fe) and manganese (Mn) are essential nutrients for humans. They act as cofactors for a variety of enzymes. In the central nervous system (CNS), these two metals are involved in diverse neurological activities. Dyshomeostasis may interfere with the critical enzymatic activities, hence altering the neurophysiological status and resulting in neurological diseases. Areas covered: In this review, the authors cover the molecular mechanisms of Fe/Mn-induced toxicity and neurological diseases, as well as the diagnosis and potential treatment. Given that both Fe and Mn are abundant in the earth crust, nutritional deficiency is rare. In this review the authors focus on the neurological disorders associated with Mn and Fe overload. Expert commentary: Oxidative stress and mitochondrial dysfunction are the primary molecular mechanism that mediates Fe/Mn-induced neurotoxicity. Although increased Fe or Mn concentrations have been found in brain of patients, it remains controversial whether the elevated metal amounts are the primary cause or secondary consequence of neurological diseases. Currently, treatments are far from satisfactory, although chelation therapy can significantly decrease brain Fe and Mn levels. Studies to determine the primary cause and establish the molecular mechanism of toxicity may help to adapt more comprehensive and satisfactory treatments in the future.

Downloaded from WILCOCK ET AL.media. This report presents the results of that review of the literature and of the evaluation of the data by Katayama et and concludes that the evidence indicates that differences exist in serious adverse drug reaction rates between ionic and nonionic CM. Content and organizationThis report first presents an overview of comparisons between ionic and nonionic CM in biological systems, including in vivo laboratory animal experiments and in vitro studies (Part I). Part I1 presents briefly the results of some recent studies comparing the effects of ionic and nonionic CM on components of the coagulation process in vitro. These findings are consistent with the concept that blood coagulation is inhibited to a greater degree by ionic iodinated CM. A description of adverse reactions to CM as reported in the smaller comparative studies involving direct comparisons of nonionic with ionic CM is included as Part 111 in order to show the concordance of findings between these studies and the Palmer'3' and Katayama et al.") studies.Part IV contains a critical evaluation of the two largest, most recent prospective studies comparing the incidence of adverse reactions associated with the use of the two kinds of contrast agents. This section includes a statement on the clinical perspective of the use of nonionic CM in radiographic procedures prepared by Harry W. Fischer, M.D. (former professor and chairman of the department of radiology, University of Rochester School of Medicine, Rochester, NY). An evaluation of the potential advantages of the use of nonionic CM over ionic CM with regard to the occurrence of severe adverse reactions can be found in Part V. Animal studies: General toxicityOverall, the acute toxicity, cardiovascular toxicity, and chemotoxicity data suggest that the nonionic CM are uniformly less toxic than the ionic CM. This finding is expected, since many of the observed toxic effects attributed to the use of CM are associated with the osmolarity of these agents relative to blood. Cardiovascular and hemodynamic aspects of CM are perhaps better studied than any other types of toxicity because of the extensive use of CM in cardiac angiography and the wealth of clinical data on cardiac function collected during such procedures, The use of nonionic CM appears to be associated with fewer cardiac-related adverse reactions than ionic CM, perhaps also due in large part to their lower osmolarity. Effect of contrast media on coagulationNonionic CM have relatively less anticoagulant activity than ionic CM. However, the clinical significance of this phenomenon is unknown. Current package inserts for both types of CM include statements about clotting potential based on in vitro studies. No new information was found that would alter the concept that ionic iodinated CM inhibit blood coagulation to a greater degree than nonionic CM.

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