Principal Developer: M. David
Secondary Developers: P. Massicotte

What is Heparin?

Heparin is an anionic mucopolysaccharide.
Heparin acts as an anticoagulant by forming a complex with antithrombin (AT). This complex inhibits several activated blood coagulation factors: XIIa, XIa, IXa, Xa and IIa (thrombin). Heparin's onset of action is immediate. It is most often used in acute conditions and must be given parenterally.
Heparin therapy in children differs from that in adults; heparin clearance is faster in the young. At birth, AT levels are 50% of adult values.
Pediatric patients often have serious underlying problems. Often other risk factors for bleeding are present.

Practical Guidelines

Standard Heparin

Intravenous regimen:

• Give IV Bolus of 75 units/kg
• For infants <1year, start infusion with initial rate of 28 units/kg/hour
  For children >1year, start infusion with initial rate of 20 units/kg/hour
• Monitor APTT every 6 hrs until therapeutic range has been achieved
• Thereafter monitor APTT and platelet count daily.

Dosage Adjustments

As for adults, the use of a heparin dosing nomogram is encouraged because it helps achieve and maintain the APTT in the therapeutic range efficiently. The following nomogram has been validated in pediatric patients > 12 months for a therapeutic range of 60 - 85 sec.

Subcutaneous regimen:

Subcutaneous injection of heparin can be very useful in pediatric patients with poor venous access. In adults, therapeutic heparin effects can reliably be achieved by subcutaneous injection as long as a sufficiently high dose is given. For children, the dose of SC heparin can be calculated from the IV requirements in the previous 24 hours and administered in two to three divided doses.

Monitoring should aim for a therapeutic APTT 4-6 hours after a subcutaneous dose. Subcutaneous catheters that remain in place for 7 days offer a relatively painless way for subcutaneous administration of heparin to children.

Low molecular weight heparin

Low molecular weight heparin is now generally preferred to standard heparin except where reversal or alteration of anticoagulant effect may be needed rapidly ie. Post operative patient at risk for bleeding but requiring anticoagulation, ECMO patients.  Recommended doses of enoxaparin are:

aiming for a therapeutic range of 0.5 to 1.0  U/ml 4 to 6 hours after the injection.

The APTT is used to monitor the effects of unfractionated heparin treatment. APTT reagents vary considerably in their sensitivity to heparin. Therefore your laboratory should establish a therapeutic range locally. In general, an adequate therapeutic effect would be achieved by an APTT ratio of 2.0-2.5 times control.

Children requiring heparin therapy frequently have underlying disorders that influence the baseline APTT and therefore the response to heparin. At birth, the APTT is prolonged, reflecting the immaturity of the coagulation system. Heparin levels may be more reliable than APTTs for monitoring heparin in newborns and some children.

Overlap with Warfarin

Generally, warfarin can be started on the same day as heparin. In the presence of pulmonary embolism or extensive proximal DVT, the initiation of warfarin may be delayed for a few days. Warfarin and heparin should overlap for at least 3 to 4 days or until the INR value is within the therapeutic range for two consecutive days before heparin is discontinued.

Teenage Pregnancy

Heparin is the anticoagulant of choice during pregnancy. Therapeutic anticoagulation with heparin can be achieved by subcutaneous injections twice daily.  Secondary prevention in the post-partum period can be achieved with warfarin or SC heparin and is recommended for approximately 6 weeks after delivery or until treatment of the acute episode is complete.  (See thrombosis in pregnancy.)

Adverse Effects

Bleeding is the most common adverse effect of heparin. If major bleeding occurs, discontinue heparin. The administration of IV Protamine Sulfate may be used to neutralize heparin's effects. With less critical bleeding, doses should be adjusted and underlying causes investigated.

Osteoporosis is a serious, but uncommon side-effect associated with prolonged use of high doses of heparin. The effect of heparin on bones in the growing child is not known. Any long-term use of heparin (ie. >3 months) should be accompanied with sensitive measurements of bone density.

Thrombocytopenia - The frequency of Heparin induced thrombocytopenia in the child has been estimated at 2%. As in adults, heparin induced thrombocytopenia thrombocytopenia is often asymptomatic but may be associated with life-threatening or fatal arterial or venous thrombosis.   It usually begins between 3 to 15 days after commencing therapy. Should it occur, stop all sources of heparin and, if necessary, alternative treatment such  as sodium danaparoid or hirudin   followed by warfarin may be used, based on anecdotal evidence. Platelet counts usually return to baseline within 4 days of stopping therapy.

This guideline was developed in collaboration with the Canadian Children's Thrombophilia Society and reviewed by T.I.G.C. members, based on medical literature and on current Canadian medical practice.

Canadian Children's Thrombophilia Society: 1-800-NO CLOTS

References:

1. Andrew et al. Pediatr Research 1994; 35:78-83
2. Massicotte P et al. J Pediatr 1996;128:313-8
3. Monagle P et al. Chest 2001; 119: 344S-370S
4. Schmugge M et al. Pediatrics 2002;109(1)E10
5. Dix D et al. J Pediatr 2000;136(4):425-6