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Apixaban Anti-Xa

CPT: 85130
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Expected Turnaround Time

2 - 5 days


Related Information


Related Documents


Specimen Requirements


Specimen

Plasma, frozen


Volume

1 mL


Minimum Volume

0.5 mL (Note:This volume does not allow for repeat testing.)


Container

Blue-top (3.2% or 3.8% sodium citrate) tube


Collection

Separate plasma from cells by centrifugation. Transfer plasma to a plastic transport tube before freezing.


Storage Instructions

Freeze. Stable at room temperature for six hours. Freeze/thaw cycles: stable x6


Causes for Rejection

Gross hemolysis; gross lipemia


Test Details


Use

To measure plasma apixaban concentration in ng/mL. Although routine monitoring is not needed, there are a number of clinical circumstances in which clinicians want or need to know a patient's apixaban level. Levels can be accurately and precisely measured using either a chromogenic anti-Xa assay or LC/MS-MS.


Limitations

The assay is not specific for apixaban and will measure any direct or indirect factor Xa anticoagulant.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).


Methodology

Chromogenic anti-Xa. Apixaban inhibition of factor Xa (present in excess). Residual Xa is measured using a chromogen and is inversely proportional to the apixaban present.


Additional Information

Clinical Information

Apixaban is an oral anticoagulant that prevents thrombin generation by inhibiting factor Xa produced as the result of both the intrinsic and extrinsic coagulation pathways.1,2 This drug inhibits free and prothrombinase-associated factor Xa in a concentration-dependent manner.3,4 Apixaban has a rapid onset reaching a maximal plasma concentration within one to three hours after oral administration.5,6 Steady-state concentrations are reached within three days with a half-life of 9 to 14 hours in healthy adults.5-7 Oral bioavailability of apixaban is not affected by food intake.4,5 Apixaban is almost insoluble in water and exhibits high plasma protein binding (87%) in humans.6 Approximately one-fourth of apixaban is excreted by the kidneys about one-half by the fecal route.5,6 Significant renal impairment results in decreased clearance and increases overall exposure to the drug.6

The P-glycoprotein (P-gp) multidrug transporter protein facilitates the transport of apixaban across cell membranes and influences the absorption and disposition of the drug in vivo.8,9 Apixaban is metabolized by the mixed function oxidase, cytochrome P450 3A4/5 (CYP3A4/5).5 Drugs that affect the activity of CYP3A4/5 and P-glycoprotein can potentially affect the pharmacokinetic profile of apixaban, Apixaban is transported across the intestinal wall by P-glycoprotein, and drugs that induce or inhibit P-glycoprotein activity may decrease or increase the levels of apixaban, respectively.

Routine therapeutic monitoring of apixaban level is not required because of the drug's relatively wide therapeutic index. Despite the use of fixed doses of apixaban, determination of the amount of drug present in a given individual may be valuable in several clinical situations, such as patients who experience bleeding or treatment failure.10,11 Determination of drug concentration may also be needed in patients who require thrombolytic therapy, surgery, or in those who have suffered trauma. It may also be of value in patients with renal insufficiency, advanced age, and low body weight.10,11 Measurement of levels can inform clinicians with concerns regarding patient compliance and adherence to therapy as well as in situations of suspected or known overdose.

Apixaban can be measured using a validated liquid chromatography/mass spectrometry (HPLC/MS-MS) method as well as a validated chromogenic anti-Xa method. Use of liquid LC/MS-MS provides highly accurate measurement of apixaban concentrations without the variable interferences associated with traditional clot-based and chromogenic assays.12 In fact, studies performed using the LabCorp LC/MS-MS method indicate that the assayed drug recovery was unaffected by the presence of lupus anticoagulants or heparin administration. Factor VIII deficiency and multiple factor deficiency associated with coumadin treatment had no effect on the recovery of drug. A chromogenic anti-Xa assay calibrated with an apixaban standard can accurately determine apixaban concentration in plasma, although this assay is not specific for apixaban and will detect any anti-Xa anticoagulant, both direct and indirect.11

Therapeutic Range

In the Aristotle trial in nonvalvular atrial fibrillation patients receiving a 5 mg bid dose yielded a median Cmax apixaban value of 171 ng/mL with a 91-321 ng/mL range for the 5th to 95th percentile. A 2.5 mg bid dose yielded a median Cmax value of 123 ng/mL with a 68.5−221 ng/mL range for the 5th to 95th percentile.13

In the AMPLIFY trial in venous thromboembolism treatment, patients receiving a 5 mg bid dose yielded a median Cmax value of 132 ng/mL with a 58.6−302.2 ng/mL range for the 5th to 95th percentile. A 2.5 mg bid dose yielded a median Cmax value of 67 ng/mL with a 29.7−153.2 ng/mL range for the 5th to 95th percentile.12


Footnotes

1. Prom R, Spinler SA. The role of apixaban for venous and arterial thromboembolic disease. Ann Pharmacother. 2011 Oct; 45(10):1262-1283. 21954450
2. Jiménez D, Yusen RD, Ramacciotti E. Apixaban: An oral direct factor-Xa inhibitor. Adv Ther. 2012 Mar; 29(3):187-201. 22354465
3. Wong PC, Crain EJ, Xin B, et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost. 2008 May; 6(5):820-829. 18315548
4. Wong PC, Jiang X. Apixaban, a direct factor Xa inhibitor, inhibits tissue factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombin. Thromb Haemost. 2010 Aug; 104(2):302-310. 20589316
5. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009 Jan; 37(1):74-81. 18832478
6. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009; 48(1):1-22. 19071881
7. Frost C, Yu Z, Moore K, et al. Apixaban, an oral direct factor Xa inhibitor: Multiple-dose safety, pharmacokinetics, and pharmacodynamics in healthy subjects. J Thromb Haemost. 2007 Aug; 5(Suppl 2):PM-664.
8. Vakkalagadda B, Frost C, Wang J, et al. Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of factor Xa (abstract 143). J Clin Pharmacol. 2009; 49:1124.
9. Frost C, Wang J, Nepal S, et al. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor (abstract 139). J Clin Pharmacol. 2009; 49:1123.
10. Cuker A. Laboratory measurement of non-vitamin K antagonist oral anticoagulants: Selecting the optimal assay based on drug, assay availability, and clinical indication. J Thromb Thrombolysis. 2016 Feb; 41(2):241-247. 26386967
11. García D, Barrett YC, Ramacciotti, Weitz JI. Laboratory assessment of anticoagulant effects of the next generation of oral anticoagulants. J Thromb Haemost. 2013 Feb; 11(2):245-252. 23216682
12. Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: Findings from the Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOLE) trial. 2015 Aug 25; 132(8):624-632. Circulation. 2015 Aug 25; 132(8):624-632. 26106009
13. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29; 369(9):799-808. 23808982

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
504385 Apixaban Anti-Xa 504386 Apixaban Anti-Xa ng/mL 74214-8

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