Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti‐factor Xa levels

Abstract

To cite this article: Schechter T, Finkelstein Y, Ali M, Kahr WH, Williams S, Chan AK, deVeber G, Brandã o LR. Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels. J Thromb Haemost 2012; 10: 368-74.Summary. Background: Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg )1 h )1 of UFH to achieve an antifactor Xa level of 0.35-0.7 IU mL )1. Objective: To assess the profile of anti-FXa-based UFH dosing guidelines in infants. Patients/Methods: We included all infants aged < 6 months treated with per-protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5-year period. Results: Of 100 infants, 11% achieved sustained therapeutic anti-FXa levels with current dose recommendations. Only 15% achieved target anti-FXa levels within 24 h with per-protocol dose escalations. Seventeen per cent of patients never achieved therapeutic antiFXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti-FXa levels in the remaining 83 infants was 33 U kg )1 h )1 (interquartile range, 30-36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding. Conclusions: UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti-FXa levels, infants monitored with the adult-based anti-FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age-appropriate ranges may be required to further improve clinical outcomes within this population.

Postthrombotic syndrome following upper extremity deep vein thrombosis in children

“…[42][43][44] The frequency of DVT resolution observed here is similar to that previously reported among pediatric patients with non-central nervous system venous thrombosis 45,46 and among children with arterial and venous thrombosis treated with standard anticoagulation. 47 Thrombolysis did not result in a significant difference in DVT resolution in our study. Although research conducted in adult patients has shown more favorable thrombus resolution with the use of catheter-directed thrombolysis and systemic thrombolysis, [48][49][50][51][52] the superiority of these modalities compared with standard anticoagulation in preventing UE-PTS is still unclear.…”

Monitoring unfractionated heparin in children: a parallel-cohort randomized controlled trial comparing 2 dose protocols

“…In a study of infants younger than 6 months of age who were treated for deep venous thrombosis with continuous UFH targeting therapeutic anti-Xa levels, many infants remained subtherapeutic despite increased UFH doses. 24 The majority of infants had thrombus regression and no recurrence, but there was an 11% risk of major bleeding. Based on these data, infants may not require increased UFH doses despite decreased UFH response based on standard laboratory tests.…”

“…Eighty-five (57%) patients were female. Overall, 78 (52%) patients were in the low-dose and 71 (48%) were in the high-dose UFH group; 94 (63%) patients were enrolled in the RCT (47 [50%] low-dose, 47 [50%] high-dose UFH), and 55 (37%) patients in the parallel cohort receiving UFH as per standard-of-care (31 [56%] low-dose, 24 [44%] highdose UFH).…”

“…1,[8][9][10][11] Several pediatric studies demonstrated poor correlation between UFH dose and its anticoagulant effect as assessed by various laboratory methods and poor agreement between the respective tests. [12][13][14][15][16][17][18][19][20][21][22][23][24] However, only 3 studies prospectively investigated the effect of a defined IV single bolus of UFH in children, and none of them compared different UFH dosage protocols or evaluated the clinical outcome regarding thrombotic or bleeding events. [21][22][23]25 Because UFH, given its short half-life and reversibility, will continue to be a preferred anticoagulant for children, systematic studies on monitoring UFH in children are needed.…”

Challenges and Priorities for Research

“…Impact of patient age, maturity, and developmental hemostasis The coagulation system in children differs significantly from adults and evolves in an asynchronous manner with growth and maturation, 7,8 affecting the pharmacology, 9,10 clearance, 11 and safety 12 of common anticoagulants, particularly heparinoids and the effect of hemodilution with routine interventions like transfusions.…”