Clinical Use Of Anti-Xa Monitoring In Malignancy-Associated Thrombosis

Low molecular weight heparin (LMWH) is currently the preferred anticoagulant for malignancy-associated venous thromboembolism (VTE) given improved outcomes compared to warfarin. However, recurrent thrombosis still occurs in up to 9% of patients despite use of this preferred agent. Data to guide clinical decisions-making in the setting of recurrent thrombosis despite use of LMWH is lacking. Unlike warfarin or unfractionated heparin (UFH), LMWH typically does not require monitoring to determine efficacy or safety. However, many providers will still check a LMWH anti-Xa level, despite little clinical validation on how these values should be interpreted and how they correspond with patient outcome. Therefore, the levels have the potential to be used or interpreted incorrectly. The aim of this study was to evaluate how LMWH anti-Xa levels are currently incorporated into clinical practice, with emphasis on whether the lab was drawn correctly, the indication for checking the level, and whether testing impacted clinical decision making.

This is a single-institution, retrospective study. Cases of malignancy-associated thrombosis occurring between 1/1/2006 and 12/31/2011 were identified using current procedural terminology (CPT) codes and the Northwestern University Electronic Data Warehouse. This cohort was then screened for those who had a LMWH anti-Xa level checked at any point in that time frame. All resultant cases had charts reviewed by 2 independent investigators to confirm active malignancy, treatment with LMWH, and history of VTE. Patients were excluded from analysis if the anti-Xa level was checked while on unfractionated heparin and if the last dose of anticoagulation was given as an outpatient.

An anti-Xa level was checked 447 times in patients with malignancy-associated thrombosis in the specified time frame. Analysis thus far was limited to the 247 patients with malignancy-associated VTE who had only one LMWH anti-Xa level checked during the study period. After reviewing for exclusion criteria, 167 cases were eligible. LMWH anti-Xa testing was sent most frequently in those with hematologic malignancy (25%) and lung cancer (13%). The indication for testing was not documented or was unclear in 88 (53%) of cases. Impaired renal function (10%), documented or suspected recurrent thrombosis despite anticoagulation (9%), and bleeding (6%) were among the more common reasons that LMWH anti-Xa levels were checked. 40% of the patients had a body mass index (BMI) ≥30. Optimal timing for testing is 4-6 hours after the third dose. In this study, the timing of the lab draw was correct in only 55% of cases, leading to potentially imprecise results in the remaining 45%. Of those drawn correctly, 76% were in the reported “therapeutic target range.” In the majority of cases, there was no change in the type or dose of anticoagulation in the 24 hours after the anti-Xa level was drawn.

Despite widespread use in routine clinical practice, the role for checking LMWH anti-Xa levels in those with malignancy-associated thrombosis being treated with LMWH is not clear. Our data indicate that providers may not be aware of how the lab should be drawn, with regard to peak levels. In addition, a majority of anti-Xa levels were checked in overweight and obese patients, despite no definitive evidence that these patients require extra monitoring. Finally, when tested correctly, the majority of patients were already in what is reported to be the therapeutic range, bringing to question if the level needed to be checked at all. This strongly suggests a role for provider education if testing is felt to be clinically indicated. At present, though testing is widely available, it is not yet clear in which clinical contexts (if any) providers should send LMWH anti-Xa levels. Prospective studies are needed to better clarify whether anti-Xa levels correlate with clinical outcomes in those with malignancy-associated thrombosis, and how the results should be incorporated clinical practice.

No relevant conflicts of interest to declare.