Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Available forms6 forms · 15 strengths documentedShow all ↓
Dalteparin 2,500 IU/mL ampoule, Fragmin
Dalteparin 12,500 IU/mL prefilled syringe, Fragmin
Dalteparin 25,000 IU/mL multidose vial or prefilled syringe, Fragmin
Enoxaparin 100 mg/mL = 10,000 anti-factor Xa IU/mL prefilled syringe, Clexane / Lovenox
1,000 USP units/mL vial
5,000 USP units/mL vial
10,000 USP units/mL vial
20,000 USP units/mL vial
Unit-dose 1,000 · 2,500 · 5,000 · 10,000 · 20,000 units/dose 0.5 or 1 mL vial, Tubex / Carpuject
Heparin sodium in 0.9% or 0.45% sodium chloride or 5% dextrose 250 to 30,000 units per bag
10 units/mL 5 mL prefilled syringe
100 units/mL 3 or 5 mL prefilled syringe
Overview
Low molecular weight heparins (LMWHs), including dalteparin and enoxaparin, are anticoagulants used in dogs and cats for the treatment of thromboembolic complications and hypercoagulable syndromes.
Compared with unfractionated heparin (UFH), LMWH has reduced anti-IIa activity relative to anti-Xa activity (anti-Xa:anti-IIa ratio of 2–4:1 versus 1:1 with UFH). At therapeutic doses, LMWH has minimal effect on activated partial thromboplastin time (aPTT), so a prolonged aPTT during treatment is a sign of overdosing. Therapeutic monitoring is based on anti-Factor Xa activity, although this may not be practical or necessary because of its more reliable and consistent pharmacokinetics.
Mechanism of Action (MOA): Low molecular weight heparin inhibits Factor Xa and thrombin, producing its anticoagulant effect.
Indications
Low molecular weight heparin is used in dogs and cats for the treatment of thromboembolic complications and hypercoagulable syndromes.
- Thromboembolic complications: Treatment of thromboembolic complications.
- Hypercoagulable syndromes: Used in hypercoagulable syndromes, including pulmonary thromboembolism and immune-mediated haemolytic anaemia (IMHA); the IMHA evidence is in dogs, and in cats IMHA is currently graded a low thrombotic risk.
Dosage
Dogs
The following dosages have been reported for low molecular weight heparins in dogs.
| Indication | Drug | Route | Dose | Frequency | Notes |
|---|---|---|---|---|---|
| Thromboembolic disease | Dalteparin | SC | 100–175 IU/kg | Every 8 hours | Not interchangeable with enoxaparin or with unfractionated heparin. |
| Thromboembolic disease | Enoxaparin | SC | 0.8 mg/kg | Every 6 hours | May not achieve anti-Xa concentrations considered therapeutic in all dogs. |
| Anticoagulation | LMWH | SC | 80–150 IU/kg | Every 4–8 hours | Enoxaparin is dosed in mg/kg: 1 mg of enoxaparin is equivalent to 100 units of anti-factor Xa. |
Cats
The following dosages have been reported for low molecular weight heparins in cats.
| Indication | Drug | Route | Dose | Frequency | Notes |
|---|---|---|---|---|---|
| Thromboembolic disease | Dalteparin | SC | 75 IU/kg | Every 6 hours | The half-life of dalteparin in cats is estimated to be 1.5 hours, which is why the interval is short. |
| Thromboembolic disease | Enoxaparin | SC | 0.75–1 mg/kg | Every 6–12 hours | The half-life of enoxaparin in cats is estimated to be 1.9 hours. |
| Anticoagulation | LMWH | SC | 80–150 IU/kg | Every 4–8 hours | Enoxaparin is dosed in mg/kg and is not interchangeable unit for unit: 1 mg of enoxaparin is equivalent to 100 units of anti-factor Xa. |
Warnings & Precautions
Low molecular weight heparin should be used with caution in patients at increased risk of bleeding, and appropriate monitoring is recommended during therapy.
- Bleeding risk: Use is contraindicated in patients with bleeding disorders, active major bleeding, or known hypersensitivity to the drug, to heparin or to pork products. Extreme caution is needed with epidural anaesthesia.
- Renal dysfunction: Contraindicated in patients with severe renal dysfunction.
- Adequate antithrombin III (AT III): Heparins are only effective if sufficient AT III is present.
- DIC: The use of LMWH in disseminated intravascular coagulation (DIC) remains controversial and is no longer recommended for prevention of DIC. If used, it should be considered only as one component of overall management, alongside treatment of the underlying cause, fluid therapy, blood products when indicated, and close monitoring of coagulation parameters.
- Therapeutic monitoring: Anti-Factor Xa activity is the preferred method for monitoring therapy, although measurement may not always be practical.
Drug Interactions
Low molecular weight heparin should be used cautiously with drugs that affect coagulation or alter its anticoagulant activity.
- Aspirin and NSAIDs: Use with caution as they may increase the risk of bleeding by altering coagulation status.
- ACTH, corticosteroids, and insulin: Heparin may antagonize their effects.
- Diazepam: Heparin may increase plasma diazepam concentrations.
- Antihistamines, digoxin, and tetracyclines: May partially counteract the anticoagulant effects of heparin.
- Administration: Do not mix other drugs in the same syringe as heparin.
- Other drugs that increase bleeding risk: Clopidogrel, oral anticoagulants such as warfarin and rivaroxaban, other factor Xa inhibitors, selective serotonin reuptake inhibitors and thrombolytic agents all increase the risk of haemorrhage when given with a low molecular weight heparin.
Side Effects & Overdose
Side Effects
Low molecular weight heparin is generally well tolerated, but bleeding-related complications may occur.
- Haematoma formation: Intramuscular administration should be avoided as it may result in haematoma formation.
- Haemorrhage: In patients with disseminated intravascular coagulation (DIC), heparin therapy may worsen haemorrhage, particularly in thrombocytopenic patients.
- Heparin-induced thrombocytopenia: A serious concern in human patients but has not been reported in dogs or cats.
Overdose
- Antidote: Protamine may be used to reverse the effects of heparin following overdose — 1 mg of protamine per 100 IU of dalteparin, or 1 mg per 1 mg of enoxaparin given within the previous 8 hours, by slow intravenous injection. Where more than 8 hours have passed, or a second protamine dose is needed, 0.5 mg of protamine per 1 mg of enoxaparin is used.
- Reversal is incomplete: In humans, protamine given for a low molecular weight heparin overdose does not completely inhibit anti-Xa activity, and no information is available for LMWH neutralisation in cats and dogs.
- Protamine risk: Give protamine only where resuscitation and treatment for anaphylactic shock are immediately available: fatal anaphylactoid reactions are recognised, and hypotension and bradycardia are reported. Do not exceed the calculated dose.
Key Notes
Practical clinical points for the use of low molecular weight heparins (LMWHs) in dogs and cats.
- Cats: Higher dosages may be required in cats to achieve the proposed therapeutic anti-Factor Xa activity — dalteparin may be increased to 150–175 IU/kg every 4 hours or up to 180 IU/kg every 6 hours, and enoxaparin to 1.25 mg/kg every 6 hours, with 1.5 mg/kg every 6 hours reported as the dose needed to hold the target activity.
- Pharmacokinetics: LMWH has more predictable and reliable pharmacokinetic properties than unfractionated heparin (UFH) in humans; in dogs and cats the half-life is much shorter, and there is currently insufficient evidence that LMWH is superior to UFH.
- Cost: LMWH is considerably more expensive than unfractionated heparin.
- Discontinuation: Rebound hypercoagulability may follow abrupt withdrawal, so the dose may need to be tapered slowly rather than stopped outright.
