fondaparinux and Anaphylaxis

Inflammatory plaques at injection sites are frequent side effects of heparin treatment and a clinical symptom of delayed-type hypersensitivity (DTH) to heparin. In most cases, changing the subcutaneous therapy from unfractionated to low-molecular-weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Because of their completely different chemical structure, hirudins are a safe alternative for anticoagulation. Despite DTH to subcutaneously injected heparins, patients tolerate heparin intravenously. Therefore, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration is justified. Skin necrosis is a rare complication of anticoagulation. Heparin-induced skin necrosis is 1 of the symptoms of immune-mediated heparin-induced thrombocytopenia and should result in the immediate cessation of heparin therapy to prevent potentially fatal thrombotic events. This is in contrast to coumarin-induced skin necrosis, where therapy may be continued or restarted at a lower dose.

Topics: Anaphylaxis; Anticoagulants; Coumarins; Drug Eruptions; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Hypersensitivity, Delayed; Polysaccharides; Thrombin; Thrombocytopenia; Vitamin K

Allergic hypersensitivity to unfractioned or low-molecular-weight heparins is uncommon but is known, and in particular the most common form is localized dermatitis, although such cases have seldom turned into maculopapular exanthema. Since cross-reactions with other heparins are frequent, identification of therapeutic alternatives is essential.. This retrospective study included patients referred to the Department of Dermatology and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and sensitized to at least one heparin (i.e. positive skin tests to at least one heparin). The heparins and hirudins used were tested in the forearm by means of intradermal skin tests. All patients were contacted in 2012 to establish whether they had used some form of heparin since the cutaneous allergy tests.. Nineteen patients had at least one positive skin test for heparin; 1 patient had presented anaphylactic shock, while 18 others had presented localized eczema (12) or generalized dermatitis (6). The heparin most often responsible for these adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests. 5/7 patients with negative skin tests had taken fondaparinux without any visible reaction, whereas 2 who also tested negative experienced localized eruption at the injection site.. Our results underline the greater frequency of delayed hypersensitivity reactions compared with immediate reactions to heparins. Skin tests can help to identify substitution molecules. Fondaparinux might be an alternative but certain diagnosis relies on rechallenge.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Anticoagulants; Cross Reactions; Dose-Response Relationship, Immunologic; Drug Eruptions; Drug Hypersensitivity; Eczema; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Hirudins; Humans; Male; Middle Aged; Polysaccharides; Retrospective Studies; Skin Tests; Young Adult

Immediate hypersensitivity to low molecular weight heparin (LMWH) is rare, and we present here a case with an anaphylaxis-like symptoms to enoxaparin. The diagnosis of hypersensitivity to enoxaparin was confirmed by the clinical picture and positive skin tests. In this case, palmo-plantal itching after application of heparin was an early sign of immediate type hypersensitivity. His skin and provocation tests showed cross-reactivity with other types of LMWHs and un-fractionated heparin (UFH). Fondaparinux and desensitization with UFH were found to be safe alternative treatment options in this patient with heparin allergy.

Topics: Adult; Anaphylaxis; Desensitization, Immunologic; Drug Hypersensitivity; Drug Tolerance; Enoxaparin; Fondaparinux; Heparin; Humans; Hypersensitivity, Immediate; Immune Tolerance; Male; Polysaccharides; Skin Tests