Aspirin desensitization


 * Associate Editor-In-Chief: Keri Shafer, M.D.

Overview
In the general population, 0.6% to 2.5% of patients will develop a hypersensitivity reaction to aspirin and that number is increased to 4.3% to 11.0% among patients with asthma. Dual antiplatelet therapy with both aspirin and clopidogrel has been associated with improved clinical outcomes in the management of patients with acute coronary syndromes. Although there is a lack of supporting data, patients with aspirin hypersensitivity are sometimes managed with clopidogrel monotherapy. Indeed, aspirin hypersensitivity has been associated with stent thrombosis in some case reports.

Aspirin desensitization is required when continued aspirin administration is essential (e.g. management of an acute coronary syndrome with stent placement). A rapid protocol can be used as described below. . While this protocol can be implemented over the course of several hours, it is not applicable to those patients who must proceed to the cardiac catheterization laboratory such as the patient with ST segment elevation myocardial infarction where "time is muscle".

Epidemiology and Demographics
The management of aspirin hypersensitivity is especially critical in patients with acute coronary syndromes. In one single center study, 26 of 1,014 patients admitted for cardiac catheterization had a history of aspirin sensitivity. Of these 26 patients, 61.5% presented with an acute coronary syndrome. While many patients could be desensitized, those with ST elevation MI could not be sensitized before the procedure.

Signs and Symptoms
The signs and symptoms of hypersensitivity include rhinorrhea, exacerbation of asthma, urticaria, angioedema, and anaphylaxis. The majority of patients develop asthma, asthma exacerbation or rhinitis.

Cross Reactivity with Other Agents
While aspirin is often the culprit, the reaction can also be induced by cross reaction with cycloxygenase 1 inhibitors (COX 1) such as ibuprofin (Motrin) and naproxen. There is also cross reactivity in patients who take acetaminophen (a weak COX 1 inhbitor), and these patients should not take more than 1000 mg as a single dose. Even 4% of patients with aspirin hypersensitivity will cross-react and sustain a cutaneous reaction to a COX-2 selective NSAID.

Mechanism of Aspirin Desensitization
The pathophysiology aspirin hypersensitivity involves both excess leukotriene producation as well as the development of IgE antibodies directed toward aspirin. The goal of a desensitization protocol is to deplete the leukotrienes (as well as other mediators) and to down-regulate the leukotriene receptors.

Protocol for Aspirin Desensitization:
In the Wong protocol, the dose of aspirin is increased every 15 minutes until the maximum dose of aspirin is administered:

Dose

0 minutes:     0.1 mg

15 minutes:    0.3 mg

30 minutes:    1 mg

45 minutes:    3 mg

60 minutes:    10 mg

75 minutes:    20 mg

90 minutes:    40 mg

105 minutes:   81 mg

120 minutes:   162 mg

135 minutes:   325 mg

Success of Aspirin Desensitization
Data regarding the success of aspirin desensitization is based upon small observational studies. Patients with chronic idiopathic urticaria often cannot be desensitized. In one single center experience, 23/26 patients (88.5%) could be desensitized. In another small singel center experience, 14/16 patients could be desensitized.

Resensitization as a Complication of Aspirin Desensitization
If patients are not treated with aspirin chronically after desensitization, they can develop resensitization. A 300 mg daily dose of aspirin was superior to a 100 mg daily dose in preventing resensitization.

The Cost-Effectiveness of Aspirin Desensitization
Aspirin desensitization is much more cost effective than clopidogrel monotherapy. Clopidogrel was associated with a cost $106,453 per incremental Quality Adjusted Life Year saved when compared with aspirin desensitization.

Guidelines Recommendations Regarding the Reduction in GI Risks Associated with Antiplatelet and NSAID Use
NSAID based GI adverse events are common and are associated with a 2 to 4 fold increase in the risk of adverse events. Recommendation: The use of low-dose ASA for cardioprophylaxis is associated with a 2- to 4-fold increase in UGIE risk. Enteric-coated or buffered preparations do not reduce the risk of bleeding. For patients at risk of adverse events, gastroprotection should be prescribed. The risk of UGIE increases with ASA dose escalation; thus, for the chronic phase of therapy, doses greater than 81 mg should not be routinely prescribed.