Heparin Sodium

Anticoagulant Antithrombotic agent (unfractionated heparin)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV Initial: 200-300 IU/kg (or 100-200 units/kg) IV bolus, then 50-100 IU/kg IV q6-8h or 10-50 IU/kg/h CRI q6-8h or CRI Duration: As needed based on clinical response and aPTT monitoring
Notes: Monitor aPTT 2-4 hours after initiation and adjust dose to maintain aPTT 1.5-2.5 times baseline. For catheter flush: 10-100 IU/mL solution.
Dog SC Prophylaxis: 100-200 IU/kg SC q8-12h q8-12h Duration: As needed
Notes: SC administration may cause bruising; use small volumes and rotate sites.
Cat IV Initial: 200-300 IU/kg IV bolus, then 50-100 IU/kg IV q6-8h or 10-50 IU/kg/h CRI q6-8h or CRI Duration: As needed
Notes: Cats may be more sensitive to heparin; monitor aPTT closely. For ATE, consider concurrent antiplatelet therapy.
Cat SC Prophylaxis: 100-200 IU/kg SC q8-12h q8-12h Duration: As needed
Notes: Use low-dose for catheter flush: 10-100 IU/mL.
Horse IV Initial: 40-80 IU/kg IV, then 20-50 IU/kg IV q8-12h or 10-20 IU/kg/h CRI q8-12h or CRI Duration: As needed
Notes: Monitor aPTT or ACT. Horses may develop anemia with prolonged use.
Horse SC Prophylaxis: 50-100 IU/kg SC q12h q12h Duration: As needed
Notes: SC administration may cause local irritation.
Cattle IV Initial: 100-200 IU/kg IV, then 50-100 IU/kg IV q8-12h q8-12h Duration: As needed
Notes: Limited evidence; use with caution. Monitor for bleeding.
Rabbit IV 100-200 IU/kg IV q6-8h (if used) q6-8h Duration: As needed
Notes: Rabbits are prone to GI ulceration; use with caution.
General (catheter flush) IV (intra-catheter) 10-100 IU/mL solution, flush with volume equal to catheter dead space As needed Duration: As needed
Notes: Use preservative-free heparin if available.

Clinical Indications & Species Uses

General Indications
  • Anticoagulation for extracorporeal circuits (e.g., hemodialysis, cardiopulmonary bypass)
  • Blood sample collection (e.g., for blood gas analysis)
  • Prevention of thrombosis in indwelling catheters
Dog (Canine)
  • Treatment of thromboembolic disease (e.g., pulmonary thromboembolism, aortic thromboembolism)
  • Prophylaxis of thrombosis in high-risk patients (e.g., immune-mediated hemolytic anemia, protein-losing nephropathy, hyperadrenocorticism)
  • Maintenance of catheter patency (low-dose flush)
  • Treatment of disseminated intravascular coagulation (DIC) (adjunctive)
Cat (Feline)
  • Treatment of arterial thromboembolism (ATE) (especially aortic thromboembolism)
  • Prophylaxis of thromboembolism in hypertrophic cardiomyopathy (HCM) with history of ATE
  • Maintenance of catheter patency (low-dose flush)
  • Treatment of DIC (adjunctive)
Horse (Equine)
  • Treatment of jugular vein thrombosis
  • Prophylaxis of thromboembolism in conditions such as colitis, endotoxemia, or post-surgery
  • Treatment of DIC (adjunctive)
Cattle (Bovine)
  • Treatment of thromboembolic disease (rarely used)
  • Prophylaxis of thrombosis in conditions such as septicemia or DIC (limited evidence)
Rabbit & Small Mammals
  • Treatment of thromboembolic disease (rarely used)
  • Maintenance of catheter patency (low-dose flush)
Exotic & Other Species
  • Maintenance of catheter patency in various exotic species (low-dose flush)
  • Treatment of thromboembolic disease in some reptiles and small mammals (limited evidence)

Pharmacology & Mechanism of Action

Drug Class: Anticoagulant | Pharmacological Group: Antithrombotic agent (unfractionated heparin)

Mechanism of Action: Heparin is a glycosaminoglycan that binds to antithrombin III (ATIII), inducing a conformational change that accelerates the inactivation of thrombin (factor IIa) and activated factor X (Xa) by ATIII. This prevents the conversion of fibrinogen to fibrin and inhibits thrombus formation. Heparin also inhibits factors IXa, XIa, and XIIa to a lesser extent. It does not have fibrinolytic activity and cannot lyse existing thrombi.

Pharmacodynamics: Heparin exerts its anticoagulant effect immediately after IV administration. The anticoagulant effect is measured by activated partial thromboplastin time (aPTT) or activated clotting time (ACT). The therapeutic range for aPTT is typically 1.5-2.5 times the baseline. Heparin also has anti-inflammatory and antilipemic effects, but these are not primary clinical uses. Its effect is reversible with protamine sulfate.

⚡ Pharmacokinetics Summary

Absorption: Heparin is poorly absorbed orally due to its large molecular weight and negative charge. It is administered parenterally (IV or SC). After SC injection, absorption is delayed but complete, with peak plasma concentrations occurring in 2-4 hours. IM administration is avoided due to risk of hematoma formation.
Distribution: Heparin is extensively bound to plasma proteins, including antithrombin III, lipoproteins, and acute-phase reactants. It has a small volume of distribution (0.05-0.1 L/kg) and does not cross the placenta or blood-brain barrier. It is taken up by the reticuloendothelial system.
Metabolism: Heparin is metabolized in the liver by the reticuloendothelial system and to a lesser extent in the kidneys. The metabolism is saturable, leading to non-linear pharmacokinetics at higher doses.
Excretion: Heparin is excreted primarily in the urine as metabolites and small amounts of unchanged drug. Renal clearance is dose-dependent. In patients with renal impairment, the half-life may be prolonged.
Half-Life: Dose-dependent: 30-60 minutes at low doses, 60-150 minutes at therapeutic doses, and up to 150-360 minutes at high doses in dogs. In horses, half-life is approximately 60-90 minutes.
Bioavailability: SC: 80-100% (but variable due to local degradation). IV: 100%.
Protein Binding: High (approximately 90% bound to antithrombin III and other plasma proteins).

Available Formulations & Strengths

Injectable Solution 1,000 IU/mL, 5,000 IU/mL, 10,000 IU/mL, 20,000 IU/mL, 40,000 IU/mL (IV, SC)
Pre-filled Syringe Various (e.g., 5,000 IU/mL) (IV, SC)
Heparin Lock Flush Solution 10 IU/mL, 100 IU/mL (Intra-catheter)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to heparin
  • Active bleeding or hemorrhagic disorders (e.g., hemophilia, thrombocytopenia with active bleeding)
  • Severe thrombocytopenia (platelet count < 50,000/µL)
  • Recent surgery or trauma with risk of bleeding
  • Bacterial endocarditis
  • Threatened abortion
  • Inability to perform adequate coagulation monitoring
Warnings & Clinical Precautions:
  • Use with extreme caution in patients with hepatic or renal impairment, as clearance may be reduced.
  • Monitor platelet counts regularly; heparin can cause heparin-induced thrombocytopenia (HIT) (rare in veterinary patients).
  • Avoid IM injections due to risk of hematoma formation.
  • Use with caution in patients with increased bleeding risk (e.g., GI ulceration, recent surgery).
  • In cats, monitor for signs of bleeding, as they may be more sensitive.
  • Prolonged use may lead to osteoporosis and alopecia (rare).
  • Do not use in animals with known hypersensitivity to pork products (heparin is derived from porcine intestinal mucosa).
  • For SC administration, use small volumes and rotate injection sites to minimize bruising.
  • In horses, prolonged use may cause anemia due to erythrocyte sequestration.
  • Antidote: Protamine sulfate should be readily available.

Adverse Effects & Reactions

Common:

  • Bleeding (e.g., injection site hematoma, epistaxis, hematuria)
  • Pain at injection site
  • Local irritation
  • Transient thrombocytopenia (mild)

Serious / Severe:

  • Severe hemorrhage (e.g., intracranial, GI, retroperitoneal)
  • Heparin-induced thrombocytopenia (HIT) (rare but serious)
  • Anaphylaxis (rare)
  • Hyperkalemia (with prolonged use due to aldosterone suppression)
  • Osteoporosis (with long-term use)

Rare:

  • Alopecia
  • Priapism
  • Skin necrosis
  • Eosinophilia
  • Elevated liver enzymes

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other anticoagulants (e.g., warfarin, direct oral anticoagulants) Additive anticoagulant effect, increased bleeding risk. High
Antiplatelet agents (e.g., aspirin, clopidogrel) Additive antiplatelet and anticoagulant effects, increased bleeding risk. High
Nonsteroidal anti-inflammatory drugs (NSAIDs) Increased risk of GI ulceration and bleeding. Moderate
Corticosteroids May increase risk of GI ulceration and bleeding. Moderate
Thrombolytic agents (e.g., tissue plasminogen activator) Additive fibrinolytic and anticoagulant effects, increased bleeding risk. High
Penicillins (high-dose IV) May prolong bleeding time and increase risk of bleeding. Moderate
Tetracyclines May decrease heparin activity (antagonistic effect). Mild
Nitroglycerin (IV) May reduce heparin's anticoagulant effect. Mild
Digoxin, quinidine, and some antihistamines May interfere with heparin's anticoagulant effect (theoretical). Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Bleeding from gums, nose, or injection sites
  • Hematuria, melena, or hematochezia
  • Ecchymosis or petechiae
  • Weakness, pale mucous membranes, tachycardia (due to blood loss)
  • In severe cases, shock or collapse

Emergency Treatment Protocol: Discontinue heparin immediately. Administer protamine sulfate IV slowly (over 1-3 minutes) at a dose of 1 mg per 100 IU of heparin administered in the previous 3-4 hours. If heparin was given SC, protamine may need to be repeated due to delayed absorption. Monitor aPTT and clinical signs. Supportive care includes fluid therapy, blood transfusion if severe hemorrhage, and oxygen therapy if needed. Note: Protamine itself can cause hypotension and anaphylactoid reactions; administer with caution.

Food Animal Withdrawal Times

🥩 Meat: 0 days🥛 Milk: 0 days🥚 Eggs: 0 days

Heparin is not approved for use in food animals in many countries. Withdrawal times are not established. In the US, extra-label use in food animals requires a withdrawal period determined by a veterinarian, but due to the short half-life, a withdrawal time of 0 days is often used. However, check local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (15-30°C). Do not freeze.

Handling & Special Conditions: Protect from freezing. Once opened, use immediately or discard. For multi-dose vials, follow manufacturer's recommendations for storage after opening.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Heparin sodium is FDA-approved for use in dogs, cats, and horses. It is not approved for food animals, but extra-label use is allowed under AMDUCA.

Extra-Label (Off-Label) Use: In the US, heparin is approved for use in animals but is not specifically approved for all species. Extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship and requires a withdrawal period. In the EU, similar rules apply under Regulation (EC) No 470/2009.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Heparin is a potent anticoagulant used in veterinary medicine for the treatment and prevention of thromboembolic disease. It is most commonly used in dogs and cats with conditions such as immune-mediated hemolytic anemia (IMHA), protein-losing nephropathy, and feline aortic thromboembolism. In horses, it is used for jugular vein thrombosis and DIC. Heparin requires parenteral administration and careful monitoring of coagulation parameters (aPTT or ACT) to avoid bleeding complications. The therapeutic range is typically 1.5-2.5 times baseline aPTT. For outpatient prophylaxis, low-molecular-weight heparins (e.g., enoxaparin) are often preferred due to more predictable pharmacokinetics and SC administration. Heparin is also used as a catheter lock to maintain patency. The antidote is protamine sulfate, which should be available when heparin is used. In food animals, use is limited due to lack of approved withdrawal times and practical considerations. Always consider the risk of bleeding versus the benefit of anticoagulation in each patient.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)