Heparin

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Unfractionated Heparin (UFH), Multiparin

ICU INDICATIONS:

1. Anticoagulation

PRESENTATION AND ADMINISTRATION:

IV:

5000 units/mL in 5 mL vials (25,000 units); other formulations also available

For this protocol, there are two different concentrations of heparin referred to below. These are bolus and infusion.

• The bolus dose is always given neat, calculated from the information in Table 1. Using a 2 mL syringe, draw up 2 mLs from one 5 mL vial of 25,000 heparin. Do not dilute. The bolus dose contains 5,000 units in 1 mL, or 10,000 units in 2 mL

• The infusion is made by adding one 5 mL vial (25,000 units of heparin) to 45 mLs of compatible IV fluid. The resultant 50 mL solution contains 500 units in 1 mL, or 100 units in 0.2 mL.

Administer via a dedicated central line or peripheral line. Discard any solution not used within 24 hours or preparation.

Compatible with the following IV fluids: 5% dextrose, Normal saline, Glucose and sodium chloride, Hartmanns

Store at room temperature

DOSAGE:

IV:

Before dosing:

• Obtain an accurate recent patient weight
• Obtain baseline APTT (normal range 21-29 seconds), INR & full blood-count
• Determine if patient is considered 'low' or 'raised' risk of bleeding when heparinised

'Raised' risk patients include:

• Post-thrombolysis
• Co-administration with clopidogrel, aspirin or NSAID
• Thrombocytopaenia
• Hypertension (Systolic >160 mmHg)
• Age > 65 years
• Liver disease (Cirrhosis or bilirubin 2x normal & AST/ALT 3x normal)
• Peptic or duodenal ulcer disease or varices
• Previous major bleeding or bleeding disposition
• Recent surgery or trauma
• Undiagnosed iron deficiency anaemia (in non-menstruating women)

Heparin in higher risk patients is not inherently safer at the reduced doses listed in the higher risk profile. Risk-based dosing is intended to reduce the risk of APTT overshoot that could contribute to bleeding in higher-risk patients.

Dosing with risk is based on the following:

• Low risk: 80 units/kg bolus, 18 units/kg/hour maintenance
• Raised risk: 60 units/kg bolus, 12 units/kg/hour maintenance

The default therapeutic APTT range for ICU patients is 50-75 seconds

Systemic heparinisation in ICU is a three stage process:

1) Initial weight-based bolus dose (charted as a Single Dose) (see Table 1)

2) Heparin IV infusion commenced at a rate determined by patient weight (see Table 2)

3) Infusion rate adjusted according to APTT (see Table 3)

STEP 1: Give the bolus dose based on the patient risk & weight from Table 1

STEP 2: Immediately commence the heparin infusion based on the patient risk & weight from Table 2

STEP 3: Measure APTT every 6 hours and perform actions described in Table 3

Do NOT adjust the infusion rate based on results taken at LESS than 6 hourly intervals

If a repeat bolus is required, refer to Table 1 for the correct dose of heparin to administer. Do not bolus from the infusion syringe as this contains a different heparin concentration.

Repeat APTT every 6 hours as long as the patient remains on heparin. Adjust infusion rate accordingly, as per Table 3.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

IV:

Make up an infusion as 500 units/kg in 50 mL 5% glucose or Normal saline

1 mL/hr = 10 units/kg/hr

Follow Starship PICU protocol

CLINICAL PHARMACOLOGY:

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin.

CONTRAINDICATIONS:

1. Severe thrombocytopaenia
2. Heparin Induced Thrombotic Thrombocytopaenia Syndrome (HITTS)

WARNINGS:

Hypersensitivity:

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations.

Haemorrhage:

Haemorrhage can occur at virtually any site in patients receiving heparin. An unexplained fall in haematocrit, fall in blood pressure, or any other unexplained symptom should lead to serious consideration of a haemorrhagic event. Heparin sodium should be used with extreme caution in disease states in which there is increased danger of haemorrhage.

Thrombocytopaenia:

Thrombocytopaenia has been described in patients receiving heparin with a reported incidence of up to 30%. Mild thrombocytopaenia (count greater than 100,000/mm³) may remain stable or reverse even if heparin is continued. However, reduction in platelet count of any degree should be monitored closely. If the count falls below 100,000/mm³ or if recurrent thrombosis develops, the heparin product should be discontinued.

PRECAUTIONS:

General:

Heparin Induced Thrombotic Thrombocytopaenia Syndrome (HITTS):

It has been reported that patients on heparin may develop new thrombus formation in association with thrombocytopaenia resulting from irreversible aggregation of platelets induced by heparin, also known as 'white clot syndrome'. The process may lead to severe thromboembolic complications like skin necrosis, gangrene of the extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and possibly death. Therefore, heparin administration should be promptly discontinued if a patient develops new thrombosis in association with a reduction in platelet count.

Heparin Resistance:

Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, in post-surgical patients, and patients with antithrombin III deficiency.

Laboratory Tests:

Patients in ICU on a heparin infusion should have their aPTT measured 6 hourly.

Drug/Laboratory Test Interactions:

None noted

Pregnancy:

Animal reproduction studies have not been conducted with heparin sodium. It is also not known whether heparin sodium can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Heparin sodium should be given to a pregnant woman only if clearly needed.

Nursing Mothers:

Heparin is not excreted in human milk.

Paediatric Use:

See DOSAGE IN PAEDIATRICS

IMPORTANT DRUG INTERACTIONS IN ICU:

Concomitant administration with warfarin, aspirin, activated protein C and enoxaparin increases the risk of bleeding.

Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant action of heparin sodium.

ADVERSE REACTIONS:

Body as a Whole:

Haemorrhage, anaphylactic reactions

Gastrointestinal System:

Nausea, vomiting

Respiratory System:

Angioedema, asthma-like symptoms

Haematological System:

Thrombocytopaenia, HITTS (see PRECAUTIONS)

Protocol Adapted from Raschke RA, et al: The weight-based heparin dosing nomogram compared with a standard care nomogram. Ann Intern Med 1993;119:874