- Also Known As:
- Anti-Xa chromogenic
- Xa Inhibition
- Anti-factor Xa Heparin
- Heparin Level
- Heparin Activity
At a Glance
Why Get Tested?
To monitor standard, unfractionated heparin (UFH) therapy and sometimes to monitor low molecular weight heparin (LMWH) therapy
When To Get Tested?
When you are being treated with UFH or LMWH and your health care provider wants to monitor the amount of heparin in your blood
A blood sample drawn from a vein in your arm
Test Preparation Needed?
What is being tested?
Heparin is a drug that inhibits blood clotting (anticoagulant) and is used to treat people who have developed dangerous blood clots (thrombi) or have a high risk of developing them. This test indirectly measures the amount of heparin in a person’s blood by measuring its inhibition of factor Xa activity, one of the proteins involved in blood clot formation (known as heparin anti-Xa activity).
The test is used to monitor heparin therapy to ensure that a person is receiving sufficient heparin for anticoagulation without causing excess bleeding. Since the test involves a chemical reaction color change (colorimetric), it is also known as chromogenic anti-Xa assay or anti-Xa assay, chromogenic.
Blood clotting is a normal response to blood vessel or tissue injury. It is a complex process that involves the activation and clumping of platelets at the site of injury and the initiation of the coagulation cascade, a sequential activation of coagulation factors, proteins that produce clots and regulate their development.
There are a variety of conditions that can cause excessive clotting and lead to the formation of blood clots within veins and arteries. Some examples include surgeries, DVT (deep vein thrombosis), and other excessive clotting disorders (hypercoagulable disorders). These clots can obstruct blood flow and cause tissue damage. Pieces of the blood clot can also break off and travel to the lungs, causing pulmonary embolism. In pregnant women, blood clot formation can sometimes occur in the placenta and affect blood flow to the developing baby (fetus) and result in a miscarriage.
Heparin may be used to prevent or treat these excessive clotting conditions (anticoagulation therapy). Through its binding to the protein antithrombin, heparin interferes with the clotting process by inhibiting clotting factors, particularly factors Xa and IIa (thrombin).
Heparin molecules vary in size and activity and there are three types of heparin that may be used for treatment:
- Standard heparin, commonly known as unfractionated heparin (UFH), is usually given through injections into a vein (intravenously, IV). UFH affects both factors Xa and IIa and has varying effects among patients, so it must be closely monitored. Complications may include clotting (insufficient heparin), excessive bleeding (too much heparin), and sometimes decrease in platelets and thrombosis (heparin-induced thrombocytopenia and thrombosis).
- Low molecular weight heparin (LMWH) consists of a narrower range of smaller heparin molecules and is typically given through injections under the skin (subcutaneous). LMWH primarily affects Xa and its effect is more predictable; therefore, routine laboratory monitoring is not required.
- Fondaparinux consists of only a small fraction of UFH (a sequence of five monomeric sugar units of heparin) and only inhibits factor Xa. It does not inhibit thrombin. Like LMWH, fondaparinux is given subcutaneously and routine laboratory monitoring is not required.
Unfractionated heparin is often used for initial treatment when excessive clotting conditions are acute. It is eventually replaced by the use of oral anticoagulants or LMWH for longer-term treatment to lower the risk of blood clots. UFH is usually given in a hospital setting and monitored with the partial thromboplastin time (PTT) test, but it may need to be monitored with the heparin anti-Xa test.
High doses of UFH given during surgeries such as cardiopulmonary bypass are typically monitored using the activated clotting time (ACT) test.
LMWH and fondaparinux may be given in either an outpatient or hospital setting. Neither LMWH nor fondaparinux significantly prolong PTT at therapeutic dosage. If monitoring is required, the anti-Xa test is used.
How is it used?
Heparin anti-Xa tests are sometimes used to monitor and adjust standard heparin (unfractionated heparin, UFH) therapy, though the primary monitoring tool for UFH is currently the PTT test. Heparin anti-Xa may be used to monitor some people who have “heparin resistance” who do not respond as expected to UFH or who have an underlying condition such as liver dysfunction or interfering factor(s) such as lupus anticoagulant (LAC) that affects the PTT test result.
Low molecular weight heparin (LMWH) and fondaparinux therapy is usually not monitored, but healthcare practitioners may order heparin anti-Xa tests in some cases. These include for women who are pregnant, people who are obese (more than 100 kg body weight), very young, or elderly and those who have kidney dysfunction. LMWH and fondaparinux are primarily cleared from the body by the kidneys. Any condition that decreases kidney function can decrease their clearance, increasing their concentration in the blood and increasing the potential for bleeding.
When is it ordered?
The heparin anti-Xa test is not routinely ordered but may be performed whenever a health care practitioner wants to evaluate UFH, LMWH, or fondaparinux concentrations in the blood.
It may be ordered periodically to monitor UFH therapy, especially when a person is not responding as expected to UFH or when the PTT is not useful.
When it is used as a LMWH and fondaparinux monitoring tool, heparin anti-Xa is primarily ordered as a “peak” test. It is typically collected about 4 hours and 3 hours after a LMWH and fondaparinux dose is given, respectively, when the level in the blood is expected to be at its highest level. Random and “trough” anti-Xa tests may also be ordered when a health care practitioner suspects that someone may not be clearing the drug at a normal rate. Trough tests are collected just prior to the next dose, when levels are expected to be at their lowest.
What does the test result mean?
Heparin anti-Xa results must be evaluated in the context of the type of heparin that a person is receiving (UFH, LMWH, or fondaparinux), 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 intervals and the heparins that they are based on vary.
In general, for heparin therapy (UFH, LMWH or fondaparinux), if test results are within an established therapeutic range and the person is doing well clinically – not clotting, bleeding excessively, or experiencing other complications – then the dosage is considered appropriate.
If the heparin anti-Xa result is high, then the person 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 heparin anti-Xa result is below the therapeutic range, then the dosage of heparin may need to be increased to prevent excessive clotting.
Is there anything else I should know?
Because of differences in the methods used for measuring heparin anti-Xa and in the test results generated by various laboratories, samples for repeat anti-Xa testing should be sent to the same laboratory.
How long will I have to receive heparin treatment?
Unfractionated heparin therapy is 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 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 typically ends around the time of delivery. After delivery, if continued anticoagulation therapy is needed, a healthcare practitioner may consider warfarin or a low molecular weight heparin such as enoxaparin.
Do I need to tell my other health care providers that I am receiving heparin?
Yes, this is information that will be important for health care practitioners to know when evaluating you for or determining treatment options for other conditions.
How are the newly approved oral anticoagulation drugs monitored?
Newly approved oral anticoagulants include direct thrombin inhibitor (e.g., dabigatran) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban). Routine laboratory monitoring of direct factor Xa inhibitor is not required. If a health care practitioner determines that monitoring is necessary, an anti-Xa test that is tailored for these drugs may be used.
On This Site
Elsewhere On The Web
National Heart, Lung and Blood Institute (NHLBI): What is Deep Vein Thrombosis?
American Academy of Orthopaedic Surgeons: Deep Vein Thrombosis
March of Dimes: Thrombophilias
NHLBI: What is Antiphospholipid Antibody Syndrome?
MedlinePlus Drug Information: Heparin Injection
Sources Used in Current Review
Wintrobe’s Clinical Hematology. 12th ed. Greer J, Foerster J, Rodgers G, Paraskevas F, Glader B, Arber D, Means R, eds. Philadelphia, PA: Lippincott Williams & Wilkins: 2009, Pp 1483-1484.
Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2011, Pp 839-840.
Harmening D. Clinical Hematology and Fundamentals of Hemostasis, Fifth Edition, F.A. Davis Company, Philadelphia, 2009, Pp 862-863.
(Dec 05, 2014) Szigeti R. Anti-Xa Assay (Heparin Assay). Medscape Review. Available online at http://emedicine.medscape.com/article/2085000-overview#a4. Accessed February 2017.
Hoffman M. Heparins: Clinical Use and Laboratory Monitoring. Laboratory Medicine. 2010;41(10):621-626. Available online at http://www.medscape.com/viewarticle/729020_6. Accessed February 2017.
(©2017) fondaparinux (Rx). Medscape Drugs and Diseases. Available online at http://reference.medscape.com/drug/arixtra-fondaparinux-342172. Accessed February 2017.
Sources Used in Previous Reviews
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry. AACC Press, Washington, DC. Pp 233-234.
Tahir, R. (2007 July 13). A Review of Unfractionated Heparin and Its Monitoring. U.S. Pharm. 2007:32(7) [On-line information]. Available online at http://www.uspharmacist.com/index.asp?show=article&page=8_2073.htm. Accessed on 6/1/08.
(2008 January, Updated). Heparin and Anti-Xa Assays]. Clot-ED [On-line information]. Available online at http://www.clot-ed.com/edit/ask_expert.html. Accessed on 6/1/08.
Schick, P. and Schick, B. (2007 April 30). Hypercoagulability: Hereditary Thrombophilia and Lupus Anticoagulants Associated with Venous Thrombosis and Emboli. emedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC3776.HTM. Accessed on 6/1/08.
O’Donnell, M. et. al. (© 2007). Brief Communication: Preoperative Anticoagulant Activity after Bridging Low-Molecular-Weight Heparin for Temporary Interruption of Warfarin. Annals of Internal Medicine 2007;146:184-187. [On-line information]. Available online at http://www.annals.org/cgi/eletters/146/3/184. Accessed on 6/1/08.
Coon, D. and Hamachi-Lopez, M. (2007 January 8). New Test Announcement, Antifactor Xa Assay. CLH Technical Bulletin 07-003 [On-line information]. PDF available for download at http://www.clhlab.com/attachment/624F6C540986B6E9E7F65D1391/LMWH.pdf. Accessed on 6/1/08.
Baglin, T. et. al. (© 2006) Guidelines on the use and monitoring of heparin. British Society for Haematology v(133) 19-34. [On-line information]. PDF available for download at http://www.bcshguidelines.com/pdf/heparin_220506.pdf. Accessed on 6/1/08.
McGlasson, D. (2005 May 25). Using a Single Calibration Curve With the Anti-Xa Chromogenic Assay for Monitoring Heparin Anticoagulation. Lab Med. 2005;36(5):297-299. [On-line information]. Available online at http://www.medscape.com/viewarticle/504792. Accessed on 6/1/08.
Hirsh, J. and Raschke, R. (© 2004). Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. CHEST 2004;126;188-203. [On-line information]. Available online at http://www.chestjournal.org/cgi/content/full/126/3_suppl/188S. Accessed on 6/1/08.
Duplaga, B. et. al. (© 2001). Dosing and Monitoring of Low-Molecular-Weight Heparins in Special Populations. Medscape from Pharmacotherapy 21(2):218-234. [On-line information]. Available online at http://www.medscape.com/viewarticle/409676. Accessed on 6/1/08.
Yeager, B. and Matheny, S. (1999 February 15). Low-Molecular-Weight Heparin in Outpatient Treatment of DVT. American Family Physician [On-line information]. Available online at http://www.aafp.org/afp/990215ap/945.html. Accessed on 6/1/08.
Harmening D. Clinical Hematology and Fundamentals of Hemostasis. Fifth Edition, F.A. Davis Company, Philadelphia, 2009, Pp 862-863, 584-585, 685-686.
Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007, Pp 780-781.
(© 1995-2011). Unit Code 80609: Heparin Anti-Xa Assay, Plasma. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/80609. Accessed November 2011.
Smith, M. and Wheeler, K. (2010 May 6). Weight-based Heparin Protocol using Antifactor Xa Monitoring. Medscape Today News from American Journal of Health-System Pharmacy. 2010;67(5):371-374. [On-line information]. Available online at http://www.medscape.com/viewarticle/720025. Accessed November 2011.
Guervil, D. et. al. (2011 August 9). Activated Partial Thromboplastin Time versus Antifactor Xa Heparin Assay in Monitoring Unfractionated Heparin by Continuous Intravenous Infusion. Medscape Today News from The Annals of Pharmacotherapy. 2011;45(8):861-868 [On-line information]. Available online at http://www.medscape.com/viewarticle/746710. Accessed November 2011.
Shapiro, N. et. al. (2011 August 1). Dosing and Monitoring of Low-molecular-weight Heparin in High-risk Pregnancy Single-Center Experience. Medscape Today News from Pharmacotherapy. 2011;31(7):678-685 [On-line information]. Available online at http://www.medscape.com/viewarticle/746233. Accessed November 2011.
Lehman, C. and Frank, E. (2009 January). Laboratory Monitoring of Heparin Therapy: Partial Thromboplastin Time or Anti-Xa Assay? ASCP LabMedicine, 40, 47-51 [On-line information]. Available online at http://labmed.ascpjournals.org/content/40/1/47.full. Accessed November 2011.