Recent history of hives while on Lovenox s/p surgery in 2010. Surgery planned for 2012 with heparin and lovenox scheduled to be used. Should skin testing with heparin and Lovenox be done, or a premedication antihistamine regimen be advised, or another alternative such as argatroban or lepirudin be recommended. I cannot find much in the literature. Thank you so much.


Thank you for your inquiry.

There is actually no "completely right or wrong" answer to your question, and in the end, the decision will be a judgment call, but there are various articles which can be of great assistance in making the decision. Based on these articles, in my opinion, if argatroban is acceptable to the surgeons, this would be my first choice. The reason for this is that it has been used successfully to substitute for heparin in a patient with heparin allergy, and the case is reported in the literature. This gives you documentation of its effectiveness and some evidence-based rationale to use this agent (see abstract by Ohno, et al., copied below).

On the other hand, in my opinion, the least desirable option would be to use heparin with antihistamine pretreatment. Although pretreatment regimens have been successful in some instances, they have also failed to protect against immediate hypersensitivity reactions as well. I could find no well established evidence that pretreatment prior to the administration of heparin would be an effective alternative for you.

Your third option, that is to evaluate by skin testing, would be, in my opinion, a suitable alternative, and you do have published protocols to help you perform such an evaluation. There is a reasonably good body of literature on this topic, and we have dealt with the issue in two previous entries on our Academy "Ask the Expert" website. Both may be helpful to you should you wish to evaluate with skin testing. These are:

Title: Immediate hypersensitivity reaction to Fragmin (dalteparin) - entered on 9/16/2011

You can access them on our website by typing "heparin" into the search box.

Finally, the other references and abstracts copied below, especially the article entitled "Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options", would be of note. The entire article is available online without charge using the link that appears below after the reference. If it does not bring up the article by clicking on this link, you can copy and paste the link into your web browser.

Thus, in summary, I believe substitution of argatroban would be my first choice. I would use it over lepirudin because I could find no article on lepirudin used for this purpose. My second choice would be to evaluate using skin tests, but this would be a distant choice, and I would use it only if argatroban was unacceptable to the surgeons.

Finally, in my opinion, the least attractive option would be to pretreat with antihistamines and then administer heparin.

Also the previous entries on our website mentioned above will give you very helpful information regarding skin testing should you choose this option.

Thank you again for your inquiry and we hope this response is helpful to you.

Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options
Allergy. Volume 61, Issue 12, pages 1432–1440, December 2006

Blood Coagul Fibrinolysis. 2006 Mar;17(2):147-9.
Fondaparinux as anticoagulant in a pregnant woman with heparin allergy.
Wijesiriwardana A, Lees DA, Lush C.
Department of Obstetrics and Gynaecology, Cumberland Infirmary, Carlisle, UK. Abstract
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.

N Z Med J. 2004 Oct 22;117(1204):U1126.
Allergic reactions to enoxaparin and heparin: a case report and review of the literature.
Tiu A, Pang JM, Martin R, Officer N

Heart Vessels. 2003 Mar;18(1):40-2.
Argatroban as an alternative anticoagulant for patients with heparin allergy during coronary bypass surgery.
Ohno H, Higashidate M, Yokosuka T.
Department of Cardiovascular Surgery, National Yokohama Hospital, 3-60-2 Harajuku, Totsuka-ku, Yokohama 245-8575, Japan.
Although heparin allergy is a rare but well-documented entity, anticoagulation management for cardiac surgery in patients with the heparin allergy has not been established due to its rarity. Here we report a case that shows our anticoagulation strategy during a coronary bypass operation. A 67-year-old man with unstable angina pectoris developed an urticarial rash 10 h after the second exposure to heparin. Results of the drug lymphocyte stimulation test were positive for porcine heparin, coumadin, and nicorandil. Off-pump coronary bypass surgery was successfully performed with argatroban as an alternative anticoagulant to heparin, with activated clotting time kept over 200 s at the rate of 5 microg/kg per min of argatroban infusion.

Phil Lieberman, M.D.

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