According to a guidance document by the Anticoagulation Forum, an optimal method for heparin monitoring is currently unknown and the current national guidelines do not prefer one method over another for heparin monitoring. Anti-Xa levels are less impacted by biological variables such as clotting factors when compared to activated partial thromboplastin time (aPTT). Both aPTT and anti-Xa results are affected by several pre-analytic and analytic variables; however, anti-Xa monitoring is more costly than aPTT and less accessible to clinicians. Benefits of anti-Xa include fewer monitoring tests, fewer dose changes, and a shorter time to reach therapeutic levels. Furthermore, anti-Xa may be useful in patients with heparin resistance, a prolonged baseline aPTT, or altered heparin response. Both aPTT and anti-Xa levels should be checked every six hours until two consecutive therapeutic levels are established. Monitoring can then be altered to once daily. [1]
The use of anti-Xa assays to monitor unfractionated heparin (UFH) levels in patients who have transitioned from direct oral anticoagulants (DOACs) may yield unquantifiable or inaccurate results that can lead to inappropriate UFH doses and treatment failures. Manufacturer labeling of oral factor Xa inhibitors does not provide specific guidance regarding this issue. Anti-Xa levels are strongly affected by oral factor Xa inhibitors, but aPTT is minorly or not affected (depending on the agent). [2]
Due to the lack of adequate guidance, a 2016 review recommends considering aPTT assay monitoring over anti-Xa monitoring in patients taking DOACs. In addition, it recommends the following strategies when converting from an oral anti-Xa inhibitor to UFH: 1) verify the time of the last anti-Xa dose; 2) initiate UFH infusion without bolus approximately two hours prior to when the next scheduled anti-Xa would have been given; 3) monitor UFH with aPTT every six to eight hours for the first 48 hours (or 72 hours for those with hepatic or renal impairments); and 4) switch to anti-Xa assay monitoring, if desired; however, consider switching back to aPTT if anti-Xa levels are above 1.10 IU/mL for two consecutive readings. [2]
Overall, there are insufficient data supporting routine monitoring of DOAC levels to predict either thrombotic or bleeding risk in a given patient. Limited data from studies that tried to use laboratory assessments only performed measurements once or twice, and they were often remote from the clinical event to correlate with drug levels. Because of short half-lives of DOACs, it is difficult to rely on traditional laboratory values (i.e., PT, aPTT, thrombin time, anti-Xa), because skipping even 1 dose alters the levels greatly. Thrombin time is very sensitive to dabigatran, and when normal; it suggests a clinically insignificant amount of dabigatran in plasma. Specific DOAC-calibrated non-FDA approved assays are available; however, not many hospitals can provide rapid results (<30 minutes). Routinely used, some heparin assays may provide sufficient information on FXa activity to make some clinical decisions. [3], [4], [5], [6]
Since there are no FDA-approved methods to monitor the anticoagulant effect of DOACs, anti-factor Xa tests can quantitatively assess anticoagulation effects. However, it should be noted that standardized therapeutic ranges have not been established for DOACs and quantitative test results have not been correlated with clinical outcomes. Qualitative coagulation assays such as activated partial thromboplastin time, thrombin time, and prothrombin time can be used as first‐line tests if an evaluation for medication compliance is clinically important; however, these tests are insufficient to assess the degree of anticoagulant effect as seen with INR for warfarin management. Currently, the only accurate monitoring for DOACs are drug trough levels, which can be used to exclude drug accumulation or when drug failure is suspected. [4], [5], [6]
A 2019 retrospective study (presented as a poster abstract) studied the anti-Xa assay "interference" when switching from a DOAC to heparin infusions in patients with renal dysfunction, on concomitant interacting medications, and with BMI > 40 kg/m^2. Patients were excluded if no interference was not met, or if the initial level did not show interference. Most of the 68 patients were on apixaban (85%) and the rest were on rivaroxaban (15%) before transitioning to heparin. The mean duration of interference was 69.3 ± 46.2 hours, and the median (interquartile range) duration was 62.7 (48–84) hours. No significant difference in duration of interference existed between patients with normal renal function compared to those with dynamic renal function (P=0.84) or with BMI > 40 kg/m^2 (P=0.16); however, patients taking interacting medications (unspecified) experienced a longer time to correct anti-Xa assays (P=0.012). [7]
Another study measured the testing interferences between DOACs and heparins in 10 healthy blood donors and 9 patients who were on a DOAC. There was no influence of dabigatran could be demonstrated in the anti-Xa testing methods for LMWH, UFH, rivaroxaban, or apixaban. All factor Xa-inhibiting drugs affected all the anti-Xa testing methods in their own specific ways. Since this data used in vitro blood samples and drug spiking for measurements, clinical considerations could not be drawn. Nonetheless, the authors suggest heparin therapy should be started only after measuring the residual concentration of the used DOAC with an appropriate assay and not before a concentration lower than 30 ng/mL has been achieved. [8]