- Protamine sulfate can be used in the event that heparin reversal is required
- Protamine combines with the strongly acidic heparin to form a stable salt complex neutralizing the anticoagulant activity
- Protamine requires a high level of caution when being prescribed and administered. Protamine should be administered IV in a concentration of 10 mg/mL at a rate not to exceed 5 mg/minute (slowly over 10 minutes). If administered too quickly it may cause cardiovascular collapse/hypotension. Patients with known hypersensitivity reactions to fish, and those who have received protamine containing insulin or previous protamine therapy may be at risk of hypersensitivity reactions to protamine sulfate
- The dosage of protamine sulfate is based on the both the amount of heparin and the time since the last dose in the previous 2 hours, up to maximum dose of 50 mg/dose, as follows:
| Time Since Last Heparin Dose (minutes) | Protamine Dose per 1 mg Heparin Received |
| <30 minutes | 1 mg per 1 mg (100 units) heparin received |
| 30-60 minutes | 0.5-0.75 mg per 1 mg (100 units) heparin received |
| 61-120 minutes | 0.375-0.5 mg per 1 mg (100 units) heparin received |
| >120 minutes | 0.25-0.375 mg per 1 mg (100 units) heparin received |
Example protamine calculation for a heparin infusion discontinued in previous 30 minutes: Multiply hourly rate (units/kg/hr) by patient weight (kg) to result in hourly heparin rate (units/hr). Multiply hourly heparin rate (units/hr) by 2 hours to result in heparin dose (units). Based on above table, 1 mg protamine is required to neutralize every 100 units of heparin if < 30 minutes since last heparin, therefore divide heparin dose (units) by 100 to result in protamine dose (mg). Do not exceed maximum 50 mg protamine per dose.
Critical site bleeds: Intracranial hemorrhage, including intraparenchymal, subdural, epidural, and subarachnoid hemorrhages; Other CNS hemorrhage, including intraocular, intra- or extra-axial spinal hemorrhages; Pericardial tamponade; Airway, including posterior epistaxis; Hemothorax, intraabdominal bleeding, and retroperitoneal hemorrhage; Extremity bleeds, including intramuscular and intraarticular bleeding concerning for compartment syndrome, bleeding associated with hemodynamic instability, bleeding in a noncompressible vessel (e.g., subclavian)
Anti-Xa, aPTT, PT may be obtained 15 minutes after administration of protamine sulfate.
