What is being tested?

This test measures the amount of low molecular weight heparin (LMWH) or unfractionated heparin (UFH) in the blood by measuring anti-Xa activity. Heparin is an anticoagulant, a drug that inhibits blood clotting. Heparin molecules vary in size and activity. UFH includes a broad range of sizes, while LMWH consists of a narrower range of smaller heparin molecules. There are several types of LMWH available and each one is slightly different. Both UFH and LMWH are given intravenously (I.V.) or through a subcutaneous injection to people who have inappropriate blood clots (thrombi) and/or are at an increased risk of developing them.

The oral anti-factor Xa inhibitors apixaban and rivaroxaban are tablets containing small components that reduce blood clotting by directly blocking the activity of factor X and therefore reducing the production of a stable blood clot by the clotting system.

Blood clotting is a normal response to blood vessel or tissue injury. It is a process that involves the initiation of the coagulation cascade - a sequential activation of coagulation factors, proteins that regulate blood clot development. There are a variety of acute and chronic conditions including surgeries, DVT (deep vein thrombosis, and other hypercoagulable disorders that are associated with inappropriate blood clot (thrombus) formation in veins and arteries – especially in the legs. These clots can obstruct blood flow and cause tissue damage in the affected area. Pieces of the blood clot can break off and travel to the lungs - causing pulmonary embolism, or to the heart – causing a heart attack. In pregnant women, blood clot formation can sometimes affect blood flow to the fetus and result in a miscarriage.

Heparin, through its action on the protein antithrombin, interferes with the clotting process by accelerating the inhibition of coagulation factors, particularly factors Xa and IIa (thrombin). UFH affects both Xa and IIa, is more variable in its inhibitory activity, and must be closely monitored. Complications may include clotting, excessive bleeding, and sometimes thrombocytopenia. UFH is usually given in a hospital setting and monitored with the activated partial thromboplastin time (APTT) test, but it may also be monitored with the anti Xa levels test. High doses of UFH given during surgeries such as cardiopulmonary bypass are monitored using the activated clotting time ATTP test. LMWH has more anti-Xa than anti-IIa activity and the response to it is more predictable. It may be given in either an outpatient or hospital setting. Routine monitoring of LMWH is not required but when it is monitored, the anti Xa levels test is used.

Apixaban and rivaroxaban do not specifically require monitoring, however in the patients who have excessive bleeding, or who require urgent interruption of these anticoagulants for a procedure or surgery with high bleeding risk, this test may be useful to clarify if it is safe to proceed with the procedure.

How is it used?

Anti Xa tests are sometimes ordered to monitor and adjust unfractionated heparin (UFH) concentrations in the blood, though the primary monitoring tool for UFH is currently the APTT test. The anti Xa levels test may be ordered to monitor some patients who have ‘heparin resistance’ – do not respond as expected to UFH – or who have an underlying condition or interfering factor(s) that alter the APTT test result.

Low molecular weight heparin (LMWH) therapy is usually not monitored, but doctors may order anti Xa tests in some cases. These include patients who are pregnant, obese, very young, elderly and those who have kidney disease or dysfunction. LMWH is primarily cleared from the body by the kidneys. Any condition that decreases kidney function can potentially decrease LMWH clearance, increasing its concentration in the blood and increasing the potential for excessive bleeding.

When is it requested?

The anti Xa levels test is not routinely ordered but may be performed whenever a doctor wants to evaluate UFH or LMWH concentrations in the blood. It may be ordered periodically to monitor UFH therapy, especially when a doctor feels that a patient is not responding as expected to UFH or when the APTT is not useful.

When it is used as a LMWH monitoring tool, anti Xa is primarily ordered as a ‘peak’ test. It is collected about 4 hours after a LMWH dose is given, when the concentration of LMWH in the blood is expected to be at its highest level. Random and ‘trough’ anti Xa tests may also be ordered when a doctor suspects that a patient may not be clearing the LMWH at a normal rate. Trough tests are collected just prior to the next dose, when heparin concentrations are expected to be at their lowest.

Apixaban and rivaroxaban anti Xa levels may be useful pre-operatively or prior to an invasive procedure to determine if the level is low enough for the procedure to occur with low bleeding risk.

What does the result mean?

Anti-Xa results must be evaluated in the context of the type of heparin that a person is receiving (UFH or LMWH and type of LMWH), the timing of the sample collection and the condition that the person is being treated for. Results from different laboratories may not be interchangeable. Therapeutic reference ranges and the heparins that they are based on vary.

In general, for UFH and LMWH, if concentrations are within an established therapeutic range and the patient is doing well clinically – not clotting, bleeding excessively, or experiencing other complications – then the dosage is considered appropriate. If the anti Xa concentration is high, then the patient may be getting an excessive dose and/or not be clearing the drug at an expected rate and may be at an increased risk for excessive bleeding.

If the anti Xa concentration is below the therapeutic range, then the dosage of heparin may need to be increased. When a person is not taking heparin, anti Xa concentrations should be zero or undetectable.

The specific anti Xa levels for apixaban and rivaroxaban vary depending upon the different testing methods used and are generally specific to the laboratory in which they are being tested. The laboratory should provide guidance on interpretation of the anti Xa levels and how this correlates with drug levels.

Is there anything else I should know?

Because of differences in the methods used for measuring anti Xa and in the test results generated by various laboratories, samples for repeat anti Xa testing should be sent to the same laboratory.

Common questions

• How long will I have to take heparin?

LMWH and UFH therapy are usually used for short periods of time to help treat and prevent inappropriate clotting. When long-term anticoagulation is required, other drug therapies such as warfarin or one of the novel oral anicoagulants (NOACs) are usually used. An exception to this is during pregnancy, when heparin is the preferred anticoagulant, but the need for heparin therapy in this case ends at the time of delivery.

• Do I need to tell my other doctors that I am receiving LMWH?

Yes, this is information that will be important for doctors and other medical professionals to know when evaluating you for or determining treatment options for other conditions.

More information

RCPA Manual: Anti-factor-Xa