Should we abandon the APTT for monitoring unfractionated heparin?

Abstract

When the anti-Xa level was 0.3-0.7IU/mL, the majority of samples from infants demonstrated a supra-therapeutic APTT, whilst adults tended to have a sub-therapeutic APTT. This may lead to under anticoagulation in infants or over anticoagulation in adults with risk of bleeding if APTT is used to monitor UFH. These results further strengthen existing evidence of the limitation of APTT in monitoring UFH. Discordance of APTT and anti-Xa level in adults and children may be due to elevation of fibrinogen level.

Intracranial Hemorrhage and Early Mortality in Patients Receiving Extracorporeal Membrane Oxygenation for Severe Respiratory Failure

“…In addition, it is our practice to monitor heparin anticoagulation using an anti-Xa assay rather than APTT which we have shown can underestimate heparin levels in these patients. 25 This may contribute to the lower incidence of major and minor bleeding (5% and 8%, respectively) seen during VV-ECMO in our study compared with 13.5% and 10.5% cannula and surgical hemorrhage, respectively, reported in the 2016 ELSO registry. 24 We did not see a significant difference in the coagulation profile of prothrombin time (PT), APTT, or fibrinogen level in patients who had ICH on admission versus those who did not, although there was a trend toward APTT prolongation.…”

Anti-Xa assays: What is their role today in antithrombotic therapy?

“…Critically ill infants and children. Arachchillage et al 35 found that infants (< 1 year old) treated with intravenous unfractionated heparin in an intensive care department had only a 32.4% correlation between aPTT and anti-Xa levels, which was lower than that found in children ages 1 to 15 (66%) and adults (52%). In two-thirds of cases of discordant aPTT and anti-Xa levels, the aPTT was elevated (supratherapeutic) while the anti-Xa assay was within the therapeutic range (0.3-0.7 U/mL).…”

“…[29][30][31][32][33] Chromogenic anti-Xa assays are available on automated analyzers with standardized kits 29,33,34 and may be faster to perform than the aPTT. 35 Experiments in rabbits show that unfractionated heparin inhibits thrombus formation and extension at concentrations of 0.2 to 0.4 U/mL as measured by the protamine titration assay, 27 which correlated with an anti-Xa activity of 0.35 to 0.67 U/mL in a randomized controlled trial. 32 Assays that directly measure the plasma concentration of heparin exist but are not clinically relevant because they also measure heparin molecules lacking the pentasaccharide sequence, which have no anticoagulant activity.…”

“…The optimal therapeutic aPTT range for treating acute venous thromboembolism should be defi ned as the aPTT range (in seconds) that correlates with a plasma activity level of unfractionated heparin of 0.3 to 0.7 U/mL based on a chromogenic anti-Xa assay, or 0.2 to 0.4 U/ mL based on a protamine titration assay. 32,[34][35][36] Nevertheless, the anticoagulant effect of unfractionated heparin as measured by the aPTT can be unpredictable and can vary widely among individuals and in the same patient. 7 This wide variability can be explained by a number of technical and biologic variables.…”

Use of Antithrombin Concentrate for Acquired Antithrombin Deficiency in Acutely Unwell Children Receiving Unfractionated Heparin

“…Although the APTT is a cheap and easily available test that is commonly used for the monitoring of UFH, it may not provide an accurate measure of anticoagulant effect of heparin as a result of various confounding factors including both preanalytical and analytical variables. 6 The anti-Xa assay is not as significantly affected by these confounding factors and so has been proposed as a better assay for monitoring UFH. Consequently, it is our standard practice to use the anti-Xa level to monitor UFH rather than the APTT in both pediatric and adult patients.…”