Mechanism of Action

• Local fibrinolysis by binding to fibrin, converts entrapped plasminogen to plasmin

Pharmacokinetics

• Half-Life: ~30-90 min.
• Metabolism: Primarily Hepatic
• Time to peak: immediate

Dosing – Pediatric

• UFH is used for the treatment of thrombosis.
• Bolus: Do not give bolus doses in neonates less than 44 weeks corrected gestational age
• Maintenance: 0.5 mg/kg/hr continuous infusion for 6 hours. Administer concurrently with low-dose UFH at 10 IU/kg/hr to prevent further thrombus formation*

Initiating Therapy

• Prior to initiation of therapy, but no longer than 48 hours before, the following labs should be checked: CBC, coagulation profile (PT, PTT, fibrinogen activity), hepatic function panel, creatinine, urine pregnancy if applicable.
• Prior to starting, a brain ultrasound is recommended for neonates less than 44 weeks corrected gestational age. It is also suggested that other high risk patients (i.e., patients < 1 year old, trauma patients, infants with recent history of cardiac surgery) undergo a brain ultrasound/imaging prior to starting UFH.
• Patients with chylous drainage via pleural catheter may have AT3 losses that effect UFH dosing
• In obese patients (BMI >95% for age), treatment dosing should be based on adjusted body weight for starting dosing.

Therapeutic initial loading dose 

heparin 75 units/kg/dose IV once infused over 10 minutes.

Do NOT give loading dose in neonates less than 44 weeks corrected gestational age, children with stroke, or when risk of bleeding is perceived to be high. A suggested maximum dose of 10,000 units/dose for some indications (excluding ECMO).

Therapeutic initial maintenance infusion

< 1 year: heparin 28 units/kg/hr IV

1-17 years: heparin 20 units/kg/hr IV

≥ 18 years: heparin 18 units/kg/hr IV

Prophylactic dosing

heparin 10 units/kg/hr IV

heparin ≤ 15 units/kg/hr can be considered prophylactic dosing

 

Monitoring Therapy

• Anti-factor Xa and aPTT are used to monitor heparin activity.
• Anti-factor Xa and aPTT levels are drawn from fresh venipuncture when possible and ideally not drawn from an extremity or line through which heparin is infusing. If drawn from heparinized line, waste should be drawn to avoid heparin contamination.
• Obtain anti-factor Xa and aPTT levels are checked 4 hours after the initial dose (not earlier), or 6 hours after start of infusion (if no bolus is administered).
• Goal anti-factor Xa is 0.35-0.7 U/mL correlates in general with aPTT of 60-85 seconds. If using aPTT, then target 1.5-2x times baseline aPTT.
• Adjust infusion to maintain therapeutic goal. aPTTs will be drawn simultaneously with all anti-factor Xa levels to ensure aPTTs are not greater than 150 seconds. If aPTT is greater than 150 seconds, consider repeating the anti-FXa and APTT by venipuncture STAT to rule out sample contamination. Monitor closely for bleeding and ensure remaining coagulation parameters (platelet count, prothrombin time, fibrinogen) are optimized.
  • Note: Anti-Xa levels may be underestimated in patients with very high levels of bilirubin or hemolysis.
  • Note: aPTT may not always be a reliable measure of heparin effect, especially in setting of nflammation or coagulopathy.
  • Note that all heparin monitoring labs should be sent STAT.

aPTT (sec)	Anti-factor Xa (units/mL)	Bolus (units/kg)	Hold (min.)	Dose change (u/kg/hr)	Repeat aPTT and anti-Xa
<50	<0.2	50*	0	Increase 20%	4 hours
50-59	0.2-0.34	0	0	Increase 10%	4 hours
60-85	0.35-0.7	0	0	0	12-24 hours When 2 consecutive anti-Xa results obtained 4 hours apart are therapeutic, obtain anti-Xa and aPTT qAM
96-120	0.71-0.8	0	0	Decrease 10%	4 hours
	0.81-0.99	0	30	Decrease 10%	4 hours
>120	>1	0	60	Decrease 15% and notify IHTC	4 hours

*Do not give bolus doses in neonates less than 44 weeks corrected gestational age

• Obtain anti-factor Xa and aPTT 4 hours after any change in infusion rate
• Once 2 consecutive anti-factor Xa obtained 4 hours apart are therapeutic, obtain anti-factor Xa and aPTT once daily.
• Other labs: CBC should be monitored daily for the first 10 days, then every 72 hours. A sudden decrease in platelet counts > 50% below baseline or below 100k should raise suspicion for heparin induced thrombocytopenia (HIT). The risk of HIT is greatest after 5 days of therapy. Maintain platelet count ≥50K to prevent excess bleeding. Heparin use is contraindicated in patients who have a history of laboratory confirmed heparin induced thrombocytopenia (HIT)
• UFH infusions should be continued without interruption through a dedicated catheter. If the maintenance infusion is interrupted for > 30 minutes, obtain anti-factor Xa and aPTT level and adjust the infusion rate as indicated above (see above Table)

Safety Precautions

• Renal impairment: No dosage adjustment requirement; adjust therapeutic heparin according to aPTT or anti-Xa activity.
• Hepatic impairment: No dosage adjustment requirement; adjust therapeutic heparin according to aPTT or anti-Xa activity.
• Drug-Drug interactions:
  • Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) may enhance the anticoagulant effect of Anticoagulants.
• Drug-Food Interactions: None
• Long term use (≥1 year) of heparin or LMWH may increase the risk of osteoporosis.
• Heparin Induced Thrombocytopenia (HIT) – Though rare, HIT does occur in children. This should be suspected in any patient on heparin, UFH or LMWH, with unexplained drop in platelet count > 50% from baseline or with thrombocytopenia.