In this episode, I’ll discuss four potential reasons for a false heparin anti-Xa level.
Monitoring heparin infusions using anti-Xa levels instead of aPTT is becoming a widespread strategy in hospital laboratories.
The main benefits of monitoring heparin by anti-Xa are said to be:
- Better correlation to actual heparin level
- Better defined target that won’t change with each reagent batch (anti-Xa level of 0.3-0.7 IU/mL)
- Less interference from hemolysis, warfarin, liver disease
The previously held disadvantages of anti-Xa are disappearing since the test is no longer cost-prohibitive and can be available on a 24/7 basis.
Despite less interference compared with aPTT, there are still clinical scenarios where the anti-Xa level may not accurately reflect the level of heparin the patient is exposed to.
1. Concurrent anti-Xa inhibitor causing false elevation
Current anti-Xa level assays are chromogenic. In the presence of factor Xa inhibition, the color change of the assay can be used to determine the exact heparin level. Color change will occur regardless of whether the factor Xa inhibition comes from heparin, apixaban, edoxaban, or rivaroxaban.
Parallel to the increase in the use of oral factor Xa inhibitors is the use of anti-factor Xa assays to monitor heparin infusions in hospitalized patients instead of aPTT.
This results in a common scenario of an anti-Xa level being extremely elevated not due to over anticoagulation but because the patient still has levels of apixaban, edoxaban, or rivaroxaban that are interfering with the test.
This interference may last several days. There is one report of this effect lasting 96 hours in a patient with poor renal function who was taking apixaban 5 mg po twice daily.
2. Drawing the anti-Xa level from an IV line contaminated with heparin
If the blood sample is from the same IV line the heparin is infusing into, the anti-Xa level may be falsely elevated. To avoid this scenario the heparin infusion needs to be paused and the line flushed, or the anti-Xa should be drawn from a different site.
Anecdotally, this scenario appears more often when inexperienced staff are drawing the levels or the patient has a single central line that is being used for blood draws and heparin infusion.
3. Hyperbilirubinemia and hypertriglyceridemia
Both elevated bilirubin and triglycerides can interfere with the chromogenic anti-Xa assay and produce a falsely elevated result. Whether this occurs may depend on the specific brand of anti-Xa assay used. For hypertriglyceridemia, the lab can use an ultracentrifuge technique to remove the interference but this is not possible with hyperbilirubinemia.
4. Antithrombin deficiency
Because the presence of antithrombin is necessary for the anticoagulant action of heparin, it is also necessary for the anti-Xa heparin assay to be accurate. If there is a deficiency of antithrombin, heparin exposure is likely higher than what the anti-Xa level suggests.
Antithrombin deficiency may be inherited but it also may be acquired. ICU patients, especially those with sepsis, may have acquired antithrombin deficiencies of almost the same magnitude as a patient with inherited antithrombin deficiency.
It may be possible for the laboratory to supplement the blood sample with antithrombin to obtain a more accurate level however this technique has not been correlated to actual patient outcomes.
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