In our cohort each patient had a
In our cohort, each patient had a median of 2 Anti-FXa measurements performed daily and a median of 1 infusion rate change daily to maintain therapeutic unfractionated heparin levels. Previously, several studies have documented that APTT-based protocols lead to more fluctuations in comparison with Anti-FXa,2, 14, 19, 31 and our study supports that Anti-FXa based monitoring of unfractionated heparin establishes better sustainability of therapeutic levels, promoting durable anticoagulation. Although a pharmacoeconomic analysis of Anti-FXa based monitoring was beyond the scope of the present study, it is likely that increased academic achievement of heparin levels would lead to fewer dose adjustments and laboratory tests, hence reducing the overall institutional costs of such testing. Failure to achieve therapeutic anticoagulation rapidly in the setting of acute thromboembolism has been associated with an increased risk of thrombus recurrence.5, 32, 33, 34 In our cohort, the time to achieve sustained therapeutic anticoagulation based on Anti-FXa levels was a median of 10 hours. Within 24 hours, three-fourths of the patients were within the therapeutic range and within 48 hours, almost all of the patients were within the goal therapeutic range. These results are in keeping with the findings of Trucco et al and support the use of Anti-FXa assay for a relatively rapid achievement of therapeutic anticoagulation. It is unclear whether this translates into improved long-term outcomes in terms of thrombus resolution, because unfractionated heparin was used only for the acute treatment of thrombosis in the hospital setting. The majority of our patients had successful treatment of their thrombi (96%); however, no marked differences were noted in the time to achieve therapeutic Anti-FXa levels between patients with or without response to therapy. In the acute phase, 7.6% of our patients had progression of their thrombi while receiving unfractionated heparin, which is comparable with the 6%-7% rate of recurrent thrombosis when APTT-based monitoring has been employed.14, 22, 35 Bleeding complications are a critical concern in children receiving anticoagulation and, in this study, the incidence of major bleeding was approximately 5%, lower than previous studies in children (11%-24%).2, 19, 20, 36 This difference is not entirely attributable to the exclusion of patients on ECMO or LVADs in the present study. Critically ill children receiving anticoagulation in the intensive care setting and immediately after cardiac surgery formed the majority of our study population (62%). Bleeding complications were independent of the age, sex, unfractionated heparin dose, platelet count, and fibrinogen level (Table IV). Previously, APTT in the supratherapeutic range has been associated with major bleeding complications.18, 20, 37, 38, 39 In our cohort, the APTT was not predictive of bleeding. Given that patients were closely monitored once the APTT was >150 seconds, and other coagulation measures were optimized, it is unclear whether the practice of obtaining APTT assays to complement Anti-FXa monitoring has any added benefit in preventing unexpected bleeding. In line with previous observations, our study found that there was moderate correlation between the APTT and Anti-FXa assays.18, 19, 21, 23, 24, 37, 40 In our cohort, when the heparin level was in the therapeutic range as measured by an Anti-FXa assay, the majority of the corresponding APTT measurements were >85 seconds, overestimating the heparin level. If the traditional APTT therapeutic range of 60-85 seconds were to be followed, based on our study, this would place patients at risk of undertreatment, relative to the Anti-FXa target. The current study has a number of limitations. It was performed at a single center, which limits its applicability to other institutions. Although the APTT and Anti-FXa assays were performed in the same laboratory, on the same analyzer, the authors were not privy to any changes made to the APTT or Anti-FXa reagents that might have occurred during the 20-month study period and their influence on the test results. However, it is unlikely that the reagents changed often enough to cause variability within each patient's test results, given that each patient was monitored for a median of 3.5 days only. Our study was not designed to be a randomized comparison between the APTT and Anti-FXa assays, and full assessment of APTT assay as a measure of anticoagulation is limited by the fact that all unfractionated heparin dose adjustments were made based on the Anti-FXa assay, as described in Table I. In addition, for the purpose of this study, an APTT range of 60-85 seconds was considered therapeutic, irrespective of age. The authors recognize the age-based variability of baseline APTT. This limits the generalizability of the current study to other institutions where a 1.5-2.5 times ratio of baseline APTT is considered therapeutic.