Heparin Sodium
Heparin sodium is a parenteral **anticoagulant** primarily utilized in veterinary medicine for the management of thromboembolic disease and, more controversially, disseminated intravascular coagulation (DIC). Key clinical applications include: - **Thromboembolic Prophylaxis**: Strong evidence supports its use in reducing macrovascular thromboembolism in high-risk patients. - **DIC Management**: Historically used for DIC, though current consensus advises against its use in DIC patients with concurrent inflammatory processes. - **Equine Medicine**: Used for laminitis prophylaxis, DIC, and as an intraperitoneal lavage to prevent post-surgical intestinal adhesions. > **Clinical Pearl**: Unfractionated heparin (UFH) has a highly variable pharmacokinetic profile compared to low-molecular-weight heparins (LMWH) like dalteparin or enoxaparin. UFH requires intensive monitoring of aPTT or anti-Xa activity to ensure therapeutic efficacy and avoid catastrophic hemorrhage.
Mecanismo: Heparin acts as an indirect anticoagulant by binding to and potentiating the activity of **Antithrombin III (ATIII)**. - **Low Concentrations**: The Heparin-ATIII complex rapidly inactivates **Factor Xa**, preventing the conversion of prothrombin to thrombin. - **High Concentrations**: The complex inactivates **Thrombin (Factor IIa)**, blocking the conversion of fibrinogen to fibrin, and also inactivates factors **IX, XI, and XII**. - **Fibrin Stabilization**: By inhibiting the activation of **Factor XIII**, heparin prevents the formation of stable fibrin clots. *Note*: Heparin does **not** lyse existing clots (it is not a thrombolytic); rather, it prevents the expansion of existing thrombi and the formation of new ones. It also increases the release of **lipoprotein lipase**, boosting the clearance of circulating lipids.
Dosificación por especie
- Adjunctive treatment of DIC · 75 Units/kg SC three times daily OR 5-10 Units/kg/hour by continuous IV infusion OR 50-100 Units/kg SC q6h · SC/IV · Variable · Doses extrapolated from general small animal guidelines in monograph.
- Feline arterial thromboembolism · 250-300 Units/kg SC q8h · SC/IV · q8h · First dose is administered IV to cats showing signs of shock.
- Maintenance therapy for arterial thromboembolic disease · 250-300 Units/kg SC every 8 hours · SC · q8h · Initial in-hospital therapy
- Prevention of complications associated with hypercoagulable states · Initially 150 Units/kg SC. Then 125 Units/kg q12h for 6 doses and then decreased to 100 Units/kg SC every 12 hours. · SC · q12h
- Adjunctive treatment of DIC · 80-100 Units/kg IV q4-6h (may be added to fluids and given as a slow drip). Low grade DIC may be treated with 25-40 Units/kg SC 2-3 times a day. · IV/SC · q4-6h or 2-3x daily
- Adjunctive therapy in endotoxic shock · 40 Units/kg IV or SC 2-3 times a day · IV/SC · q8-12h · May prevent the development of microthrombi.
- Adjunctive therapy in the prevention of laminitis · 25-100 Units/kg subcutaneously 3 times daily · SC · q8h · Higher doses used when a thrombotic event is underway.
- Prevention of abdominal adhesions · 30,000-50,000 Units heparin in 10 L of lavage fluid (warm LRS) administered intraperitoneally · Intraperitoneal · At 12, 18, 36, and 48 hours post-surgery · 48 hours · Administered via a 32 french fenestrated trocar catheter.
Vías de administración
Contraindicaciones
- Known hypersensitivity to heparin
- Severe thrombocytopenia
- Uncontrollable bleeding (not caused by DIC)
- Intramuscular (IM) administration (causes hematomas)
- Actively bleeding DIC patients with severe factor depletion
Efectos adversos
- Hemorrhage (most common)
- Thrombocytopenia
- Hypersensitivity reactions (derived from bovine/porcine tissue)
- Anemia in horses (due to erythrocyte agglutination)
- Injection site pain and hematoma (especially if given IM)
- Vasospastic reactions
- Osteoporosis (with long-term use)
- Rebound hyperlipidemia
- Hyperkalemia
- Alopecia
Interacciones farmacológicas
- Aspirin · May increase the risk for hemorrhage
- Dextran · May increase the risk for hemorrhage
- NSAIDs · May increase the risk for hemorrhage
- Warfarin · May increase the risk for hemorrhage
- Antihistamines · May partially counteract heparin's anticoagulant effects
- Nitroglycerin (IV) · May partially counteract heparin's anticoagulant effects
- Propylene Glycol · May partially counteract heparin's anticoagulant effects
- Digoxin · May partially counteract heparin's anticoagulant effects
- Tetracyclines · May partially counteract heparin's anticoagulant effects
Monitoreo
- Activated partial thromboplastin time (aPTT) - most often recommended
- Whole blood clotting time (WBCT)
- Partial thromboplastin time (PTT)
- Activated clotting time (ACT)
- Thromboelastography (TEG)
- Platelet counts
- Packed cell volume (PCV) / Hematocrit
- Occult blood in stool and urine
- Clinical signs of bleeding or efficacy
Sobredosis
Overdosage of heparin is directly associated with **severe bleeding**. Clinical signs preceding frank hemorrhage include: - Hematuria - Tarry stools (melena) - Petechiae and ecchymoses (bruising) **Reversal**: **Protamine sulfate** can be administered to reverse heparin's anticoagulant effects. It binds to heparin to form a stable, inactive complex.
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