Slide 1: People with fish allergies are at risk for anaphylactic reaction to which medication?

Slide 2: Protamine sulfate. Protamine sulfate was originally isolated from salmon sperm. It is clinically used as a heparin reversal agent. How? First, let’s review how heparin works.

Heparin prevents clot formation by binding and activating antithrombin, which subsequently inactivates other participants in the coagulation cascade.

Graphic showing heparin activation of antithrombin. Active antithrombin inhibits thrombin and factor Xa to prevent clot formation.

Slide 3: Protamine works by binding to heparin and preventing it from activating antithrombin.

Graphic showing protamine binding to and inactivating heparin.

Slide 4: Salmon protamines are small nuclear proteins that help stabilize and fold DNA in the salmon sperm head. Case reports suggest that those with fish allergies are at higher risk of severe protamine sulfate allergies.

Protamine is also a key component of NPH (neutral protamine Hagedorn) insulin, a intermediate-acting insulin formulation. The suspension of protamine mixed with insulin leads to slow release of insulin into the bloodstream. Those who use NPH insulin are also at risk of anaphylactic reaction to protamine.

Slide 5: Bringing it all together! Since protamine is often used during cardiovascular procedures for heparin reversal (cardiac catheterization, cardiac bypass, major vascular surgeries), all patients with regular NPH insulin use and/or fish allergies who are undergoing these procedures should be closely monitored for allergic reactions to protamine sulfate.

References

  • Boer C, Meesters MI, Veerhoek D, Vonk ABA. Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review. Br J Anaesth. 2018 May;120(5):914-927. PMID 29661409.
  • Brück S, Skrabal C, Träger K, Reinelt H. Kasuistik mit Literaturübersicht – Protamingabe bei Patientin mit Fischeiweißallergie [Risk factors for adverse reactions after protamine administration in adult patients undergoing cardiac surgery- a case report and literature review]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2014 Jun;49(6):360-6. German. PMID 25004379.
  • Vincent GM, Janowski M, Menlove R. Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations. Cathet Cardiovasc Diagn. 1991 Jul;23(3):164-8. PMID 1831070.

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