fondaparinux and Drug-Hypersensitivity

Non-immediate allergic cutaneous reactions to heparins have been increasingly reported, typically manifesting as large, eczematous plaques at sites of subcutaneous injection. Patients may demonstrate cross-reactivity between unfractionated heparin, low molecular weight heparin and semi-synthetic heparinoids, making finding an alternative difficult. Fondaparinux has been identified as a useful alternative in such patients; here we present the first two documented cases in Australia and a literature review.

Topics: Adult; Anticoagulants; Drug Hypersensitivity; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Heparinoids; Humans; Hypersensitivity, Delayed; Injections, Subcutaneous; Middle Aged; Polysaccharides

Topics: Anticoagulants; Antithrombins; Drug Hypersensitivity; Drug Substitution; Fondaparinux; Heparin; Heparinoids; Humans; Immunologic Tests; Platelet Activation; Platelet Factor 4; Polysaccharides; Thrombocytopenia

To determine the incidence and causes of skin reactions to the synthetic pentasaccharide fondaparinux.. Patients who received prophylactic/therapeutic subcutaneous fondaparinux treatment for more than 7 days were prospectively examined for cutaneous adverse effects between September 1, 2008, and April 30, 2009. When indicated, other procedures, such as skin biopsy, allergy testing, and clinical/laboratory assessment for thrombosis and heparin-induced thrombocytopenia, were performed.. Overall, 231 patients were enrolled. No patient developed typical delayed type IV hypersensitivity (DTH) erythematous skin lesions. However, one female patient experienced abdominal pruritus at sites of injection. Histology revealed a mild lymphohistiocytic infiltrate, confirming a DTH reaction. Heparin-induced thrombocytopenia, as another possible underlying pathomechanism for cutaneous lesions, was ruled out clinically and serologically. Hence, the overall incidence of fondaparinux-induced allergic skin lesions was 0.4% (95% confidence interval, 0.01%-2.4%). No cross-allergies were observed in patients with DTH reaction to heparins.. Fondaparinux has a low allergenic potential. The incidence of allergic cutaneous DTH reactions is almost 20 times lower compared to that with commonly used heparins. These results, together with the known low prevalence of secondary thrombotic events or heparin-induced thrombocytopenia during fondaparinux therapy, suggest that in selected patients fondaparinux might substantially improve patient care, therapeutic safety, and cost-effectiveness of anticoagulant therapy.. clinicaltrials.gov identifier: NCT00510432.

Topics: Anticoagulants; Biopsy; Dose-Response Relationship, Drug; Drug Hypersensitivity; Factor X; Female; Follow-Up Studies; Fondaparinux; Germany; Humans; Incidence; Injections, Subcutaneous; Male; Middle Aged; Nadroparin; Polysaccharides; Prognosis; Prospective Studies; Pulmonary Embolism; Severity of Illness Index; Skin; Skin Tests

Topics: Adult; Aged; Anticoagulants; Drug Hypersensitivity; Female; Fondaparinux; Heparin; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Polysaccharides

Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An important differential diagnosis is circumscribed skin necrosis due to heparin-induced thrombocytopenia.. An inflammatory skin reaction to subcutaneously injected heparin generally entails the quest for alternative anticoagulation; concerns may particularly arise in an emergency situation requiring intravenous heparin administration.. All heparin DTH cases seen in our department over the last 17 years underwent standardized allergy diagnostics including challenge testing, that is, subcutaneous injection of fondaparinux and intravenous administration of unfractionated heparin (UFH).. Of a total of 50 patients with confirmed heparin allergy, DTH was found in 48 (96.0%), and immediate-type, presumably IgE-mediated hypersensitivity was diagnosed in only 2 (4.0%). In the 48 DTH cases, intradermal testing revealed broad cross-reactivity between UFH and low-molecular-weight heparins (LMWH) including nadroparin, dalteparin, and enoxaparin. Cross-reactivity with (or concomitant sensitization to) fondaparinux was seen in only 3 (6.3%) cases. Intravenous administration of UFH was tolerated by all 45 patients challenged, despite DTH to UFH and LMWH as demonstrated by intradermal testing.. If an inflammatory skin reaction at the site of subcutaneously injected heparin is observed or reported without any evidence of skin necrosis or thrombocytopenia, intravenous administration of UFH seems to be sufficiently safe and may be considered without allergy testing if urgently indicated in an emergency situation. Fondaparinux is the most suitable alternative for subcutaneous application.

Topics: Administration, Intravenous; Anticoagulants; Drug Hypersensitivity; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Necrosis; Skin Tests

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Hypersensitivity, Immediate; Middle Aged; Polysaccharides; Tinzaparin; Venous Thrombosis

Topics: Abortion, Spontaneous; Adult; Anticoagulants; Drug Hypersensitivity; Drug Substitution; Female; Fetal Death; Fondaparinux; Heparin; Humans; Intradermal Tests; Polysaccharides; Predictive Value of Tests; Pregnancy; Risk Factors; Thrombocythemia, Essential; Treatment Outcome

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

The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort.. Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start.. Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred.. Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Topics: Adult; Aged; Anticoagulants; Drug Hypersensitivity; Drug Prescriptions; Female; Fondaparinux; Germany; Hemorrhage; Heparin; Hospitals, University; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Risk Assessment; Risk Factors; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

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

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adrenal Cortex Hormones; Anticoagulants; Breast Neoplasms; Drug Hypersensitivity; Enoxaparin; Female; Fondaparinux; Histamine Antagonists; Humans; Hypersensitivity, Delayed; Lung Neoplasms; Middle Aged; Nadroparin; Patch Tests; Polysaccharides; Treatment Outcome; Vena Cava, Superior; Venous Thrombosis

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fondaparinux; Heparin; Humans; Lupus Erythematosus, Systemic; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Skin Tests; Thromboembolism

Topics: Adult; Anticoagulants; Drug Hypersensitivity; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Heparinoids; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thromboembolism; Venous Thrombosis

We report a patient who had a history of deep vein thrombosis in a previous pregnancy. She was treated with heparins without any reactions in the index pregnancy. Subsequently, when the patient became pregnant again, she developed an acute cutaneous reaction to the low molecular heparin enoxaparin 3 weeks after initiation of therapy. She developed a similar reaction to delteparin as well. She was therefore treated with warfarin until 36 weeks of gestation. Then she was treated with fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) 2.5 mg daily for the remainder of the pregnancy. Delivery was at term by induction of labour. Fondaparinux was stopped on the day of the induction of labour. It was re-started 6 h post-delivery and the patient was anticoagulated with warfarin in the post-partum period. There were no bleeding tendencies or recurrences of thrombosis during fondaparinux therapy. Both mother and baby were well after delivery.

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Live Birth; Polysaccharides; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Cross Reactions; Dalteparin; Drug Hypersensitivity; Factor V; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Hypersensitivity, Immediate; Polysaccharides

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Hypersensitivity, Delayed; Injections, Subcutaneous; Middle Aged; Polysaccharides

Topics: Anticoagulants; Drug Eruptions; Drug Hypersensitivity; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Molecular Weight; Polysaccharides; Venous Thrombosis

Topics: Adult; Anticoagulants; Drug Eruptions; Drug Hypersensitivity; Female; Fondaparinux; Heparin; Humans; Hypersensitivity, Delayed; Polysaccharides; Skin Tests

During the last decade, new anticoagulant drugs with anti-factor-Xa properties have been described (1, 2). Among them is fondaparinux that has been licensed recently. It is a pentasaccharide mimicking the site where heparin binds to antithrombin III (1). This new drug has produced very promising clinical results in the prophylaxis of venous thrombosis after orthopedic surgery (3). Here we report two different clinical situations in which fondaparinux has yielded a successful outcome: first, a patient with repeated cutaneus reaction to several different low molecular weight heparins (LMWH), and second, a patient with severe heparin-induced thrombocytopenia (HIT). We decided to use fondaparinux in both cases since it is commercially available in Spain and mostly because the absence of in vitro cross-reaction with heparins, as discussed later.

Topics: Abortion, Induced; Acute Kidney Injury; Adenocarcinoma; Adult; Aged; Autoimmune Diseases; Combined Modality Therapy; Drug Eruptions; Drug Hypersensitivity; Endometrial Neoplasms; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Lupus Erythematosus, Systemic; Polysaccharides; Postoperative Complications; Pregnancy; Thrombophilia; Thrombosis

Topics: Aged; Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Middle Aged; Pentosan Sulfuric Polyester; Polysaccharides; Skin Tests