Protamine sulfate is used as an antidote to neutralize the anticoagulant effect of heparin.

- Heparin is an anticoagulant that works by activating antithrombin III, which in turn inhibits thrombin and factor Xa, leading to the prevention of blood clot formation.
- When excessive anticoagulation occurs, it may lead to bleeding complications.

- Protamine sulfate is a positively charged protein that binds to the negatively charged heparin, forming a stable complex that neutralizes its anticoagulant activity.
- This interaction rapidly reverses the effect of heparin, making protamine sulfate the specific antidote for heparin overdose or bleeding due to heparin therapy.

- Warfarin anticoagulates by inhibiting vitamin K-dependent clotting factors and is reversed with vitamin K, not protamine.
- Aspirin and Clopidogrel inhibit platelet function; their effects are not reversed by protamine sulfate but may require platelet transfusions or other measures.

Key points:
- Protamine sulfate specifically neutralizes heparin.
- Neutralization occurs via ionic binding between protamine (positive) and heparin (negative).
- Protamine sulfate is ineffective against warfarin, aspirin, or clopidogrel.

Reference: *Harrison's Principles of Internal Medicine, 20th Edition, Volume 2, Chapter 103: Disorders of Hemostasis and Thrombosis*