Dose and Administration

Maintenance of patency of arterial and/or central venous catheters.

1. Continuous infusion: 0.5 unit/ml of solution for maintenance of patency of arterial catheters, central venous catheters and umbilical venous catheters.
2. In IVN solutions - all solutions contain 0.5 units/ml.

Intermittent heparin flushes:

1. Peripheral IV lines no longer flushed with heparin  - use 0.5ml of 0.9% NaCl Q12H.
2. Longlines, UACs and UVCs are to be primed with and flushed with 0.9% NaCl during insertion.
   After insertion, flush with 0.5ml of 10U/ml Heparin.
3. For intermittent flushing of longlines and CVLs that are luered, use 0.7ml of 10U Heparin per ml flush after each medication.  We strongly recommend removal of the line if it is no longer required, except under exceptional circumstances.

Full dose heparinisation for anticoagulation:

1. Loading dose 75 units/kg by IV injection over 10 minutes.  Higher loading doses may need to be considered in special cases but this should be discussed with the specialist responsible for the patient.
2. Commence maintenance dose at 28units/kg/hour by continuous intravenous infusion and titrate dose by assessment of clinical effects and clotting studies.

Notes about Titration of Heparin Anticoagulation:

1. Ensure a baseline APTT has been performed.
2. The target APTT for anticoagulation is 50-80 seconds.
3. The normal APTT in term neonates and babies up to 30 days of age is 31-55 seconds.
   • Note that the upper limit in normal babies overlaps with the target APTT.  This reflects the relative immaturity of neonatal haemostasis. 
4. Heparin-induced thrombocytopenia is less common in neonates but the platelet count should be checked 24-hours after starting the heparin and every 2-3 days whilst on treatment.
5. Review the need for continuing heparin treatment in 5-7 days and consider other forms of anticoagulation as appropriate.

• APTT is used to monitor unfractionated heparin treatment and is reagent/instrument specific.  The current target APTT values from the ADHB laboratory is 50-80 seconds for either the venous or capillary APTT.  The laboratory will notify the clinical area if there is a change in target values but if in doubt please check with the laboratory.
  • APTT can be determined on venous blood collects in a citrate tube.
  • The laboratory also provides a capillary APTT service between 8am and midnight for heparin monitoring.
    Please discuss the capillary APTT service with the laboratory haematologist through the Haemostasis Section, Haematology Laboratory, as soon as possible when heparin treatment is being considered.
• If heparin dose adjustment is made as soon as possible after the APTT result is available, the capillary APTT can be monitored around 8:30am, 1:30pm, 6:30pm, and midnight, if necessary.  APTT outside these hours should be checked on a venous sample (available 24-hours a day).The dosing protocol above aims to bring the APTT within the therapeutic range within 24-48 hours, but recent studies indicate (in adults) provided an adequate dose as stated above the clinical outcome is the same regardless of whether the APTT is within the therapeutic range within the specified time.
• APTT monitoring is important to prevent overdose with the associated bleeding risk.
• Clinical staff are responsible for dose adjustment and informing the laboratory whether and when the subsequent test is required.

Low Dose Heparin

1. Ensure a baseline APTT has been done.
2. No loading dose is given.
3. The dose is fixed at 10u/kg/hour unless the APTT is unduly prolonged.
4. APTT is checked 4-6 hours after the infusion is commenced and then daily if the APTT is <45 seconds.
5. If the APTT is 45-50 seconds, reduce the heparin to 8u/kg/hour then check 4-6 hours later.
6. If the APTT is >50 seconds, reduce the heparin to 5u/kg/hour then check 4-6 hours later.
7. Please see above for APTT monitoring.

Indications

1. Maintenance of patency of arterial catheters, umbilical and central venous catheters, and luered CVLs and longlines.
2. Neonatal thrombosis.
3. Disseminated intravascular coagulation.

Contraindications and Precautions

1. Known hypersensitivity to heparin.
2. Presence of uncontrollable bleeding, bleeding tendencies.
3. Intraventricular haemorrhage, gastrointestinal haemorrhage.
4. Thrombocytopaenia < 50 x 109/L.
5. Severe hepatic, biliary or renal dysfunction.
6. Severe hypertension.
7. Eye, brain or spinal cord surgery.
8. Ascorbic acid deficiency.

Clinical Pharmacology

Heparin activates antithrombin III, which progressively inactivates both thrombin and factor Xa, key proteolytic enzymes in the formation of fibrinogen and the activation of prothrombin. Also possesses anticomplementary activity, inhibiting both the classic and alternative pathways. Not clinically significant at serum heparin levels associated with therapeutic anticoagulant doses of heparin.

Some oral absorption but lack of anticoagulant effect. Rapidly taken up by endothelial cells with remainder bound to plasma proteins. Hepatic metabolism. Elimination via the kidneys (only small quantities of unchanged heparin).

Possible Adverse Reactions

1. Haemorrhage, haematomas.
2. Hypersensitivity reactions (fever, rash, nasal congestion, asthma, anaphylaxis, alopecia).
3. Transient mild thrombocytopaenia.
4. Renal impairment.
5. Hyperaldosteronism.

Special Considerations

1. Maternal heparin therapy is not a contraindication to breast feeding, as heparin does not pass through breast milk.
2. Management of heparin overdose and/or toxicity:
   • Stop heparin
   • Administer protamine sulphate (1 mg per 100 units of heparin received by infant in previous 3-4 hours IV by slow infusion over 10 minutes. Do not exceed 5mg/min, maximum dose 50 mg).