PB0150 - Discordant dose-response to Enoxaparin observed in Anti-Xa Low Molecular Weight Heparin monitoring of a paediatric patient with hyperbilirubinaemia

Background: A 7-month-old patient with cholestatic hepatitis was prescribed low molecular weight heparin (Enoxaparin) to treat portal vein thrombosis and was monitored daily with the Anti-Xa LMWH assay. Anti-Xa levels were subtherapeutic despite escalating Enoxaparin doses while the activated partial thromboplastin time (APTT) clotting time was progressively prolonged.

Aims: We aim to examine the lack of correlation between Enoxaparin dosage and Anti-Xa activity and demonstrate the effect of hyperbilirubinaemia as an interference to chromogenic Anti-Xa testing.

Methods: We reviewed the patient’s clinical data on the electronic medical record and carried out laboratory investigations to explore possible pre-analytical interferences. STA Compact Max analyser utilises colorimetric measurement of residual FXa activity to determine the inhibitory effect of Enoxaparin.

Results: Common pre-analytical issues were ruled out after checking the specimens for clot, incorrect fill volume and delay in processing. The specimens were found to be icteric which were confirmed by high serum bilirubin ranging from 363 to 461 μmol/L. Anti-Xa level at the onset of therapy was subtherapeutic ( < 0.50 IU/ml) and remained subtherapeutic despite increasing Enoxaparin dose from 5mg BD to 12 mg BD while the corresponding APTT was appropriately prolonged (> 60.0 seconds). It took 6 days and a high Enoxaparin dose of 15mg BD (3.4mg/kg/dose) to reach the therapeutic Anti-Xa level (0.5 to 1.0 IU/ml).

Conclusion(s): Our findings agree with previous publications which cited evidence that icteric specimens from patients with hyperbilirubinaemia can increase the optical density (OD) measurement of FXa activity, leading to underestimation of heparin activity. Since hyperbilirubinaemia cannot be resolved through redrawing of specimens or ultracentrifugation, clot-based APTT should be considered for heparin monitoring. Clinicians and laboratory scientists must be aware of pre-analytical interferences when interpreting Anti-Xa results in the context of hyperbilirubinaemia.