Immediate type hypersensitivity reactions due to heparins are rare, and the exact immunologic pathomechanism has not been identified so far. In our 2 case reports, we describe first a 50-year-old female who received dalteparin (Fragmin®) and developed signs of an immediate type hypersensitivity reaction. The personal history revealed a previous application of dalteparin (Fragmin®). Evaluation with a skin prick test showed positive results for dalteparin. The second case deals with a 73-year-old female with a suspected immediate type reaction after the administration of dalteparin (Fragmin®). A skin prick test was negative but intracutaneous tests showed a positive reaction to the causative agent. Both cases indicated cross-reactivity reactions for low-molecular-weight heparin (LMWH) but not for unfractioned heparin (UFH) or fondaparinux. In conclusion, our case reports including a review of published cases of immediate type hypersensitivity reactions after the application of heparins illustrate this rare complication. Mostly, the causative agent can be identified with a skin test, which is highly suggestive of an IgE-mediated reaction. Therapeutic alternatives for patients with sensitization to an LMWH are UFH and fondaparinux. Both agents have a small risk of cross-reactivity compared to heparins of the same substance class.

1.
Gray E, Mulloy B, Barrowcliffe TW: Heparin and low-molecular-weight heparin. Thromb Haemost 2008;99:807-818.
[PubMed]
2.
Arepally GM, Ortel TL: Clinical practice: heparin-induced thrombocytopenia. N Engl J Med 2006;355:809-817.
[PubMed]
3.
Bircher AJ, Harr T, Hohenstein L, Tsakiris DA: Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options. Allergy 2006;61:1432-1440.
[PubMed]
4.
Kishimoto TK, Viswanathan K, Ganguly T, Elankumaran S, Smith S, Pelzer K, Lansing JC, Sriranganathan N, Zhao G, Galcheva-Gargova Z, et al: Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med 2008;358:2457-2467.
[PubMed]
5.
Schindewolf M, Lindhoff-Last E, Ludwig RJ, Boehncke WH: Heparin-induced skin lesions. Lancet 2012;380:1867-1879.
[PubMed]
6.
Bottio T, Pittarello G, Bonato R, Fagiolo U, Gerosa G: Life-threatening anaphylactic shock caused by porcine heparin intravenous infusion during mitral valve repair. J Thorac Cardiovasc Surg 2003;126:1194-1195.
[PubMed]
7.
Tiu A, Pang JM, Martin R, Officer N: Allergic reactions to enoxaparin and heparin: a case report and review of the literature. N Z Med J 2004;117:U1126.
[PubMed]
8.
Basic-Jukic N, Kes P: Severe anaphylactic reaction in a haemodialysis patient after administration of reviparin. Nephrol Dial Transplant 2004;19:1021-1022.
[PubMed]
9.
Parissis H: Lepirudin as an alternative to “heparin allergy” during cardiopulmonary bypass. J Cardiothorac Surg 2011;6:44.
[PubMed]
10.
Berkun Y, Haviv YS, Schwartz LB, Shalit M: Heparin-induced recurrent anaphylaxis. Clin Exp Allergy 2004;34:1916-1918.
[PubMed]
11.
Ueda A, Nagase S, Morito N, Yotsumoto M, Ohba S, Hasegawa Y, Narita M, Koyama A: Anaphylactoid reaction induced by low-molecular-weight heparin in a hemodialysis patient. Nephron 2001;87:93-94.
[PubMed]
12.
Caballero MR, Fernandez-Benitez M: Allergy to heparin: a new in vitro diagnostic technique. Allergol Immunopathol (Madr) 2003;31:324-328.
[PubMed]
13.
Bekkenk MW, van Zuuren EJ: Immediate type hypersensitivity after injection of nadroparin (Fraxiparin). Thromb Haemost 2005;94:673-674.
[PubMed]
14.
Harr T, Scherer K, Tsakiris DA, Bircher AJ: Immediate type hypersensitivity to low molecular weight heparins and tolerance of unfractioned heparin and fondaparinux. Allergy 2006;61:787-788.
[PubMed]
15.
Kavut AB, Koca E: Successful desensitization with un-fractionated heparin in a patient with heparin allergy and tolerance to fondaparinux. Asian Pac J Allergy Immunol 2012;30:162-166.
[PubMed]
16.
Anders D, Trautmann A: Allergic anaphylaxis due to subcutaneously injected heparin. Allergy Asthma Clin Immunol 2013;9:1.
[PubMed]
17.
Gelardi M, Ciprandi G, Buttafava S, Quaranta N, Squeo V, Incorvaia C, Frati F: Nasal inflammation in Parietaria-allergic patients is associated with pollen exposure. J Investig Allergol Clin Immunol 2014;24:352-353.
[PubMed]
18.
Balthazar S, Watremez C, Vigneault L, Eeckhoudt S, Pirson F, Hermans C: Management of anticoagulation during cardiopulmonary bypass in a patient with allergy to heparin and heparin-like compounds: a case-report. Blood Coagul Fibrinolysis 2014;25:900-903.
[PubMed]
19.
Pfohler C, Muller CS, Pindur G, Eichler H, Schafers HJ, Grundmann U, Tilgen W: Delayed-type heparin allergy: diagnostic procedures and treatment alternatives - a case series including 15 patients. World Allergy Organ J 2008;1:194-199.
[PubMed]
20.
Gonzalez P, de la Sen ML, Venegas I, Ramon A, Soriano V, Cueva B, Fernandez J: Immediate hypersensitivity to heparins: a cross-reactivity study. J Investig Allergol Clin Immunol 2014;24:367-368.
[PubMed]
21.
Weberschock T, Meister AC, Bohrt K, Schmitt J, Boehncke WH, Ludwig RJ: The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review. Contact Dermatitis 2011;65:187-194.
[PubMed]
22.
Maetzke J, Hinrichs R, Staib G, Scharffetter-Kochanek K: Fondaparinux as a novel therapeutic alternative in a patient with heparin allergy. Allergy 2004;59:237-238.
[PubMed]
23.
Petitou M, Herault JP, Bernat A, Driguez PA, Duchaussoy P, Lormeau JC, Herbert JM: Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature 1999;398:417-422.
[PubMed]
24.
Gaigl Z, Pfeuffer P, Raith P, Brocker EB, Trautmann A: Tolerance to intravenous heparin in patients with delayed-type hypersensitivity to heparins: a prospective study. Br J Haematol 2005;128:389-392.
[PubMed]
25.
Jappe U: Allergy to heparins and anticoagulants with a similar pharmacological profile: an update. Blood Coagul Fibrinolysis 2006;17:605-613.
[PubMed]
26.
Scherer Hofmeier K, Bircher AJ: Hypersensitivity reactions to modern antiplatelet and anticoagulant drugs. Allergo J Int 2015;24:58-66.
[PubMed]
You do not currently have access to this content.