fondaparinux and Dermatitis--Allergic-Contact

Heparins are a widely used class of drugs known to cause delayed-type hypersensitivity (DTH) reactions. Recent publications indicate that the incidence of these may be higher than previously thought. To date, patient-related but no drug-related risk factors for the development of DTH reactions to heparins have been identified, although molecular weight is discussed as a potentially relevant parameter.. To address this, a systematic review was conducted on the frequency of cross-reactions after DTH reactions to heparin preparations.. We electronically searched MEDLINE and EMBASE, hand-searched selected journals and references, and contacted experts for unpublished data.. Sixty-six publications and unpublished data of 14 patients resulted in 198 patients with 1084 tests for cross-reactivity. The primary causative agents were mostly unfractionated heparin (50%) and low molecular weight heparins (49.5%). Cross-reactions were more likely after an initial DTH reaction to unfractionated heparin than after an initial DTH reaction to low molecular weight heparin. Our findings also indicate that molecular weight does not correlate with the risk for cross-reactivity, which is in line with recent observations, indicating that different heparins have to be individually considered.. The available data demonstrated the lowest overall risk for cross-reactions for pentosan polysulfate (36.4%) and fondaparinux (10.4%). In the clinical context, fondaparinux is recommended as the current best alternative when a DTH reaction occurs.

Topics: Anticoagulants; Cross Reactions; Dermatitis, Allergic Contact; Drug Eruptions; Female; Fondaparinux; Heparin; Humans; Incidence; Male; Pentosan Sulfuric Polyester; Polysaccharides; Risk

Topics: Aged, 80 and over; Anticoagulants; Dermatitis, Allergic Contact; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudins; Humans; Polysaccharides; Recombinant Proteins

Topics: Aged; Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Dermatitis, Allergic Contact; Drug Tolerance; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Skin

Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood. Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their alpha- and beta-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.

Topics: Adult; Aged; Anticoagulants; Cross Reactions; Dermatitis, Allergic Contact; Female; Fondaparinux; Heparin; Humans; Middle Aged; Molecular Structure; Polysaccharides; Skin Tests

Topics: Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Dermatitis, Allergic Contact; Drug Eruptions; Female; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Risk Factors; Time Factors