Protamine sulphate reverses unfractionated heparin (UFH) but only PARTIALLY reverses low molecular weight heparin (LMWH). The molecular reason is:

• A LMWH binds antithrombin III more tightly than UFH, preventing protamine displacement
• B LMWH is renally cleared and protamine acts only on hepatically cleared fragments
• C Protamine inhibits anti-IIa (thrombin) activity of heparin but has no effect on anti-Xa activity of either heparin
• D Protamine neutralises anti-Xa activity of LMWH but the shorter LMWH chains (bound to anti-Xa) interact less with protamine, leaving significant residual anti-Xa activity ✓

Explanation

Protamine sulphate (a positively charged protein) binds heparin (negatively charged polysaccharide) via electrostatic interaction, forming an inactive complex. UFH has long chains with both anti-Xa and anti-IIa (thrombin) activities, and protamine fully neutralises both. LMWH has shorter saccharide chains that mediate anti-Xa activity (binding a pentasaccharide to AT-III + Xa). These shorter chains bind protamine less efficiently, so while anti-IIa activity of LMWH is fully reversed, only ~60% of anti-Xa activity is reversed. Residual anti-Xa activity remains.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.