LAUSR

To the Editor: Epidemiologic studies from Canada and the Netherlands estimated the incidence of venous thrombo-embolism (VTE) to be 0.07 to 0.14/10,000 children (and neonates), respectively.1,2 A recent study, however, has indicated a 70% increase in the annual rate of VTE in hospitalized children from 2001 to 2007.3 This increase is likely an outcome of improved survival of critically ill children with multiple comorbid conditions and increased use of central venous lines (CVL).3 Unfractionated heparin (UFH), low–molecular-weight heparins and warfarin are the most commonly used anticoagulants in children. Given its short half-life and immediate, complete reversibility with protamine sulfate, heparin remains the therapeutic modality of choice for critically ill children, children on extracorporeal membrane oxygenation (ECMO) and children with left ventricular assist devices (LVADs). A prospective audit of UFH use in a tertiary care children’s hospital indicated that 15% of children admitted to the inpatient service were exposed to UFH.4 The activated partial thromboplastin time (APTT) has historically been used to monitor heparin anticoagulation. The traditional anticoagulation range of APTT (1.5 to 2.5 times the control) in children receiving UFH is based on a prospective, adult study which documented a low risk of recurrent thrombosis with an APTT >1.5 times the control.5 APTT measurement, particularly in children, is affected by several confounders—(i) baseline APTT is prolonged in neonates and infants, additionally infants have low levels of natural anticoagulants, (ii) faster clearance of heparin in infants and younger children, and (iii) elevated levels of factor VIII and fibrinogen in critically ill children may cause shortening of the APTT.6–8 The current American College of Chest Physicians (ACCP) guidelines recommend that the APTT range in children on UFH anticoagulation correspond to an antiFactor Xa (FXa) activity of 0.35 to 0.7U/mL or a protamine titration range of 0.2 to 0.4U/mL. Recent pediatric publications, however, report a poor correlation between APTT and anti-FXa activity.9–13 While many children’s hospitals are transitioning from an APTT-based dose adjustment nomogram to an anti-FXa-based nomogram, it is unclear if this change is associated with improved patient outcomes with regards to bleeding and/ or recurrent VTE.9