Aprotinin


Aprotinin is a naturally occurring polybasic polypeptide serine protease inhibitor, purified from cattle lungs. It is used in cardiac surgical procedures. It decreases blood loss and transfusion requirements (30 to 40%) by its antifibrinolytic effect, platelet preservation, anti-inflammatory effect and possible preventive action on CNS injury.
 
Incidence
0.5% of allergic reactions.
 
2.1% to 5.8% if re-exposure.
 
Between 1964 and 1993: 26 cases have been reported (3 deaths).
 
Risk factors
Interval of less than 200 days between two aprotinin exposures; especially 35 days to 2 months.
 
Clinical manifestations
General: anaphylactic shock.
 
Respiratory: bronchospasm.
 
Cutaneous: localized or generalized urticaria.
 
Diagnostic methods
Cutaneous testing.
 
Skin-prick tests, then intradermal skin tests from 1/1000 to 1/10: a few cases with positive skin tests after an allergic reaction.
 
Specific IgE and IgG
 
After 48 months, 50% of all patients still show measurable levels of IgG antiaprotinin.
 
IgE and IgG antiaprotinin are found in 55% of patients with allergic reactions and 32% of non-reactors. Thus, clinical value is not clearly established.
 
Mechanisms
IgE-mediated hypersensitivity.
 
Non-specific histamine release.
 
Management
Do not use aprotinin in non-cardiovascular surgery.
 
Delay the first bolus injection of aprotinin until the surgeon is ready to begin cardiopulmonary bypass.
 
Test dose of 10000 KIU of aprotinin in all patients with aprotinin treatment.
 
H1/H2 blockade (clemastine 0.03 mg/kg + cimetidine 5 mg/kg) in cases of known or possible previous exposure.
 
Avoidance of re-exposure within the first 6 months after the previous exposure to aprotinin.
 
Use predictive skin-tests in patients with previous exposure or beef-allergic.
 
Other antifibrinolytics are available (tranexamic acid).

References

  1. Dobkowski W.B, Murkin J.M, "A risk-benefit assessment of aprotinin in cardiac surgical procedures", Drug. Saf, 1998; 18 (1): 21-41
  2. Dietrich W, Spath P, Ebell A, Richter J.A, "Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight re-exposures to aprotinin in heart operations", J. Thorac. Cardiovasc. Surg., 1997; 113 (1): 194-201
  3. Scheule A.M, Jurmann M.J, Wendel H.P, Haberle L, Eckstein F.S, Ziemer G, "Anaphylactic shock after aprotinin re-exposure: time course of aprotinin-specific antibodies", Ann. Thorac. Surg., 1997; 63 (1): 242-4
  4. Cottineau C, Moreau X, Drouet M, De Brux J.L, Brenet O, Delhumeau A, "Choc anaphylactique lors de l’utilisation de l’aprotinine à fortes doses en chirurgie cardiaque", Ann. Fr. Anesth. Reanim., 1993; 12 (6): 590-3
  5. Yanagihara Y, Shida T, "Immunological studies on patients who received aprotinin therapy", Arerugi., 1985; 34 (9): 899–904.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.