Streptokinase


Streptokinase is a 47000 D protein produced by Beta hemolytic streptococci. Once bonded with plasminogen the streptokinase-plasminogen complex cleaves arginine 560 on free plasminogen molecules from free plasma.
 
Clinical uses of streptokinase include the treatment of acute myocardial infarction, deep venous thrombosis, arterial thrombosis and embolism.
 
Incidence
ISIS-2 trial: 4.4% of allergic reactions to streptokinase.
 
ISIS-3 trial: 3.6% of allergic reactions to streptokinase.
 
GUSTO-1 trial: 5.7% of allergic reactions to streptokinase (0.6% anaphylaxis).
 
Risk factors
Previous exposure to streptokinase: topical (6 months), antithrombotic use (4 years).
 
Clinical manifestations
Anaphylactic shock.
 
Bronchospasm, ARDS.
 
Rash, periorbital swelling.
 
Rhinorrhea, sneezing.
 
Delayed reactions: fever, arthralgias, myalgias, cutaneous eruptions, renal abnormalities.
 
Diagnostic methods
Cutaneous testing.
 
Skin-prick tests with streptokinase 300 000 IU/ml.
 
Intradermal skin tests: 0.02 ml of 3 IU and 10 IU streptokinase.
 
Some cases positive in patients with anaphylaxis.
 
Serologic methods.
 
Precipitating antibodies.
 
Antistreptokinase IgE, IgG, IgM (ELISA).
 
Antistreptokinase IgG (fluorimetric assay; fibrinplate assay).
 
Lymphocyte transformation test (one case).
 
Mechanisms
Complement activation.
 
Human albumin, phosphate buffers, and sodium glutamate are contained in streptokinase preparations.
 
IgE-mediated hypersensitivity: positive skin-tests, specific IgE.
 
Type III hypersensitivity: serum sickness, vasculitis, glomerulonephritis.
 
The presence of antistreptokinase antibodies in high titers may lead to a lower rate of coronary reperfusion if streptokinase is reused.
 
Management
Use alteplase or urokinase in patients previously exposed to streptokinase.
 
The biologic efficacy of streptokinase is not compromised by an allergic reaction.
 
The precise relation between streptokinase allergy, antibody titers, and clinical outcome requires further studies.
 
Hydrocortisone and antihistamines appear to have no protective effect against hypotensive reactions.
 
Perform an intradermal skin-test with 100 IU of streptokinase before intravenous use.
 
If positive do not use streptokinase; a negative skin-tests is predictive of safe administration of streptokinase.
 
Rapid enzyme immunoassay of antistreptokinase antibodies in human plasma (in 30 minutes) should allow the best thrombolytic therapy for the patient.

References

  1. Tsang T.S, Califf R.M, Stebbins A.L, Lee K.L, Cho S, Ross A.M, Armstrong P.W, "Incidence and impact on outcome of streptokinase allergy in the GUSTO-1 trial", Am. J. Cardiol., 1997; 79 (9): 1232-5 
  2. Jennings K, "Antibodies to streptokinase (editorial)", B.M.J, 1996; 312 (7028): 393-4 
  3. Lee H.S, "How safe is the re-administration of streptokinase ?", Drug Safe., 1995; 13 (2): 76-80 
  4. Lynch M, Pentecost B.L, Littler W.A, Stockley R.A, "The significance of anti-streptokinase antibodies", Clin. Exp. Immunol., 1994; 96 (3): 427-31 
  5. Lee H.S, Yule S, Mc Kenzie A, Cross S, Red T, Davidson R, Jennings K, "Hypersensitivity reactions to streptokinase in patients with high pre-treatment anti-streptokinase antibody and neutralization titres (see comments)", Eur. J. Heart., 1993; 14 (12): 1640-3 
  6. Dykewicz M.S, Mc Grath K.C, Davison R, Kaplan K.J, Patterson R, "Identification of patients at risk for anaphylaxis due to streptokinase", Arch. Intern. Med., 1986; 146 (2): 305–7.

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