Hypersensitivity Reactions to Anticoagulant Drugs

Abstract

Drugs with anticoagulant activity, including heparins, hirudins, coumarins, and platelet aggregation inhibitors belong to the most widely used drugs. Hypersensitivity reactions from these agents are rare. However, due to their widespread use, they may have a considerable impact on patient safety and treatment. Accurate diagnosis of potentially life-threatening adverse events and identification of alternatives is mandatory. We review hypersensitivity reactions caused by the different groups of anticoagulant agents and discuss the pathophysiological mechanisms, diagnostic possibilities and management options. According to patients histories the most common hypersensitivity reaction is intolerance to acetylsalicylic acid (ASA). Also localized erythematous plaques, occurring to subcutaneous application of heparins are rather common. Other hypersensitivity reactions are rare but may be life-threatening, e.g. skin necrosis due to heparin-induced thrombocytopenia. Rarely anaphylactoid reactions have been observed to ASA, heparin, and hirudin. Skin and provocation tests with immediate and late readings are the most reliable diagnostic tools for heparin- or hirudin-induced urticaria/anaphylaxis or heparin-induced delayed plaques. Provocation tests may be used to identify safe alternatives. In cases of necrosis from heparins or coumarins, all in vivo tests are contraindicated. Most in vitro tests are not universally available, and with the exception of platelet aggregation tests, they have a low sensitivity. In some anticoagulant-associated hypersensitivity reactions detailed allergologic investigation may help to identify safe treatment alternatives. Typically, several tests are needed, and therefore the test procedures are time consuming.

Low Allergenic Potential With Fondaparinux: Results of a Prospective Investigation

“…2,3 Besides bleeding complications, heparin-induced skin lesions are the most frequent adverse effects of subcutaneous heparin therapy. [4][5][6] Patients typically present with itching and eczematous plaques that occur predominantly at heparin injection sites; however, presentations can vary (Figure 1, top). 4,5 In a recent prospective investigation of patients receiving subcutaneous heparin therapy, 7 we observed an incidence of 7.5% for heparin-induced skin lesions that could be classified as lymphocyte-mediated delayed type IV hypersensitivity (DTH) reactions (Figure 2, A).…”

Immediate Type Hypersensitivity to Heparins: Two Case Reports and a Review of the Literature

“…Heparins may provoke type I to type IV hypersensitivity reactions; particularly delayed type hypersensitivity (DTH) reactions (type IV) are common [3]. After a latency of 2-10 days to 3 weeks, infiltrating eczematous plaques can develop locally at the injection sites.…”

“…Histological findings are lympho-histiocytic dermal infiltration and spongiosis of the epidermis. Only rarely generalized maculopapular exanthemas and exceptionally Lyell syndrome have been described [3,5]. The most dangerous hypersensitivity reaction to systemic heparin use is heparin-induced thrombocytopenia (HIT II), a type II antibody-mediated hypersensitivity reaction against complexes of platelet factor 4 and heparin [2].…”

“…However, immediate type hypersensitivity reactions (type I) are very rare and only a few documented cases have been published so far [3]. A recent epidemic of anaphylactic reactions to heparins could be related to oversulfated heparin molecules resulting in activation of the contact system [4].…”

Oropharyngeal angioneurotic edema due to recombinant tissue plasminogen activator following massive pulmonary thromboembolism

“…But the fact that orolingual edema is absent in transfusion reaction clinic and orolingual edema following rtPA in patients using ARB has been established in the literature, the clinical situation has been associated with valsartan. However, the fact that pulmonary embolism developed under fractionated heparin treatment and heparin induced hypersensitivity reactions are mostly type II and type IV reactions, and the fact that isolated orolingual edema has not been reported with heparin, it was omitted in the differential diagnosis [12].…”