Our suggested approach to titrating systemic unfractionated heparin infusion in neonates based upon anti-Xa levels and aPTT

aPTT: activated partial thromboplastin time; UFH: unfractionated heparin; ULN: upper limit of normal; CBC: complete blood count; PT: Pprothrombin time; INR: international normalized ratio; DIC: disseminated intravascular coagulation.
* If the anti-Xa level is persistently low despite multiple dose adjustments, some experts would measure the neonate's antithrombin level and supplement if low.
¶ If the anti-Xa level is persistently high despite multiple dose adjustments, the neonate's renal function should be evaluated. In addition, heparin contamination of the blood sample should be excluded.
Δ The ULN for aPTT is higher in neonates compared with older children and adults. However, not all laboratories reflect this in their reference ranges for aPTT and neonates may be incorrectly flagged as having a high baseline aPTT. In such circumstances, the aPTT on heparin therapy should be interpretted relative to the baseline (pretreatment) aPTT rather than the ULN of the reference range.
◊ Dose adjustments for the UFH infusion according to anti-Xa levels are as follows:

• Anti Xa ≤0.1 – Give bolus of 50 units/kg, then increase maintenance infusion by 10%; the bolus dose should be withheld or reduced if there are significant bleeding risks (eg, extremely low birth weight, septicemia)
• Anti Xa 0.11 to 0.34 – Increase maintenance infusion by 10%
• Anti Xa 0.35 to 0.7 – No change
• Anti Xa 0.71 to 0.99 – Decrease maintenance infusion by 10%
• Anti Xa 1.0 to 1.19 – Hold infusion for 30 minutes, then restart at a dose reduced by 10%
• Anti Xa ≥1.2 – Hold infusion for 60 minutes, then restart at a dose reduced by 15%

§ Low PTT values despite therapeutic or supratherapeutic anti-Xa levels may be seen if the factor VIII level is elevated. Factor VIII levels can be elevated during active thrombosis, and baseline factor VIII levels are higher in neonates compared with older children and adults. Thus, if the patient has discordant aPTT and anti-Xa levels in this manner, checking the factor VIII level can help explain why the aPTT is low despite therapeutic or supratherapeutic anti-Xa levels. The finding of an elevated factor VIII level confirms that the anti-Xa level is the more reliable measure of anticoagulant activity. In such cases, the clinician should rely on the anti-Xa level rather than the aPTT for subseuent dose titration. No additional intervention is needed to specifically address the elevated factor VIII level.
¥ If there is a disconnect between the 2 values such that the anti-Xa level is subtherapeutic yet the aPTT is >1.5 × ULN, the UFH dose should not be increased to achieve the desired therapeutic anti-Xa level, since there are reports of serious bleeding occurring in this setting, particularly in neonates. Consultation with a pediatric hematologist is advised.
‡ A common cause of prolonged aPTT is heparin contamination in the blood sample. If this has been excluded, other causes include DIC, liver disease, and vitamin K deficiency.