Heparin-induced Thrombocytopenia PF4 Antibody
- Also Known As:
- Heparin-PF4 Antibody
- HIT Antibody
- HIT PF4 Antibody
- Heparin Induced Antibody
- Heparin Associated Antibody
- Formal Name:
- Heparin-induced Thrombocytopenia Platelet Factor 4 Antibody
At a Glance
Why Get Tested?
To detect antibodies against the anticoagulant heparin, to help diagnose immune-mediated heparin-induced thrombocytopenia (HIT II)
When To Get Tested?
When you are receiving heparin therapy and your platelet count significantly decreases (thrombocytopenia), especially when you also have new blood clots (thrombosis)
A blood sample drawn from a vein in your arm
Test Preparation Needed?
What is being tested?
Heparin-induced thrombocytopenia is a complication of treatment with the blood-thinner (anticoagulant) heparin that can cause low platelets in the blood and an increased risk of excessive blood clotting. This test detects and measures antibodies that may be produced by your immune system when or after you are treated with heparin.
Heparin is a common anticoagulant that is given intravenously or through injections to prevent the formation of inappropriate blood clots (thrombosis) or as an initial treatment when you have a blood clot, to prevent the clot from enlarging. It is often given during some surgeries, such as heart surgery (cardiopulmonary bypass), when the risk for developing blood clots is high. Small amounts of heparin are frequently used to flush out catheters and intravenous lines to keep clots from forming in them.
Sometimes, when you are given heparin, the drug can combine with a substance found in platelets called platelet factor 4 (PF4) and form a complex. In some people, the body’s immune system recognizes the heparin-PF4 complex as “foreign” and produces an antibody directed against it. This antibody in turn can activate your platelets and lead to a drop in the number of platelets, a condition known as heparin-induced thrombocytopenia (HIT). It may also lead to the development of new thrombosis or worsening thrombosis, which is a potentially life-threatening complication of heparin use.
Platelets are cell fragments that are an important part of your blood clotting system. When a blood vessel is injured and leaks blood, platelets are activated and clump together at the site of the injury, and work with coagulation factors to promote clot formation and stop the bleeding.
Not everyone on heparin produces HIT antibodies, and not everyone with HIT antibodies develops a low platelet count, but about 1% to 5% of those with the antibodies do.
- In HIT, the antibodies bind to the heparin-PF4 complexes, which then attach to the surface of platelets. If this happens, it activates your platelets, which in turn, triggers the release of more PF4.
- This starts a cycle that can cause a rapid and significant drop (e.g., 50% or more) in the number of platelets in your blood.
- Usually, a decrease in platelets results in a higher risk of bleeding, but in HIT, the activation of platelets by HIT antibodies can paradoxically lead to new and progressive blood clot formation in your veins and arteries.
- This cycle occurs in about 30% to 50% of those who develop the HIT antibody and thrombocytopenia.
This condition, associated with the presence of HIT antibody, low platelet count, and excessive clotting, is formally called immune-mediated heparin-induced thrombocytopenia or HIT type II. If this happens, it typically develops about 5-10 days after you start heparin therapy but may also develop rapidly, within 1-2 days, if you have been treated with heparin in the last 3 months and start heparin treatment again.
There is also a non-immune mediated HIT (type I) that occurs when heparin binds directly to platelets, causing activation. It is more common than type II but is temporary and a milder form and is of no clinical significance.
How is the test used?
A test for heparin-induced thrombocytopenia (HIT) antibody, also called heparin-PF4 antibody, is performed to detect antibodies that develop in some people who have been treated with heparin. It is used to help establish a diagnosis of immune-mediated heparin-induced thrombocytopenia (HIT type II) when you have a low platelet count (thrombocytopenia) and excessive clotting (thrombosis).
Even if you have detectable HIT antibodies, you will not necessarily develop HIT II. Therefore, this test is most useful in those with a moderate to high likelihood of having HIT II, based upon the timing of heparin use, significantly low platelet count, and excessive blood clotting. The test is typically ordered along with or following a platelet count and may be followed by additional tests such as functional assays to help confirm a finding.
Functional assays, such as a serotonin release assay or heparin-induced platelet activation assay, are more specific for HIT II but take longer, are more technically demanding, and not widely available. These tests measure the effect your serum has on the function of “normal” platelets from healthy donors.
When is it ordered?
Since the development of HIT antibodies does not always lead to HIT II, testing is usually ordered only when HIT II is clinically suspected.
There is a pre-test scoring system that is typically used to determine your likelihood of having HIT II. It includes:
- How low your platelet count has dropped (platelet decrease of 50% or more from before you were treated with heparin therapy)
- The timing of the platelet count fall (typically 5-10 days after initial heparin use and within 2 days for a second use within 3 months of previous use)
- The presence of new blood clots (thrombosis) and/or lesions at the heparin injection site
- Ruling out other causes of low platelet count
The HIT antibody test is performed when this pre-scoring test shows that you have a moderate to high likelihood of having HIT II.
Typically, an enzyme immunoassay (EIA) that detects HIT antibody is ordered as an initial test. Functional testing such as a serotonin release assay (SRA) or heparin-induced platelet activation (HIPA) test may be ordered when the EIA test is indeterminate or negative but suspicion of HIT is still high.
What does the test result mean?
The interpretation of HIT antibody results relies upon testing only people who have a moderate to high probability of having HIT II. Both false negatives and false positives can occur with this test and are more likely if you have a low probability of having HIT II.
If you have HIT antibodies, have been treated with heparin for 5 to 10 days, have a platelet count that has decreased by 50% or more, and have new blood clots, then it is likely that you have HIT II.
If you have HIT antibodies, have received heparin within the last 3 months and are experiencing significant thrombocytopenia within a day or two of re-starting heparin therapy, then it may also indicate HIT II.
If HIT testing is indeterminate, confirmatory testing is positive, and you have clinical signs of HIT, then it is likely that you have HIT II.
If the test is negative for HIT antibodies, then it is unlikely that you have HIT II. If confirmatory testing is performed and it is also negative, then it is likely that your symptoms are due to another cause.
Does everyone with HIT antibodies develop HIT II?
No. In fact, the majority of people who produce HIT antibodies will not develop HIT II (i.e., have significant thrombocytopenia and thrombosis).
What else can cause a low platelet count (thrombocytopenia)?
Many conditions and diseases other than HIT can cause thrombocytopenia by affecting your platelet production or increasing platelet loss (destruction). In addition to heparin, there are several other medications that can cause drug-induced thrombocytopenia and antiplatelet antibodies.
What is HIT type I and how does it differ from HIT type II?
Heparin-induced thrombocytopenia type I (HIT type I) may be seen when you are receiving heparin, but HIT I tends to be a more mild condition that is not associated with an immune reaction and is typically of no clinical significance.
Does the type and/or amount of heparin I receive make a difference in my risk for developing HIT?
There are two types of heparin that may be used in your treatment: standard or unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). HIT II can develop in anyone receiving UFH but is more likely in those who have had surgery. The condition is rare in children. Low molecular weight heparin (LMWH) does not generally cause HIT II, but it can. If you have developed HIT II with UFH, then you are more likely to develop HIT with LMWH.
It is rare but possible for you to develop HIT antibodies, even when the only heparin that you have been exposed to is the small amount used to flush out your intravenous line or catheter.
Can the heparin-induced thrombocytopenia (HIT) antibody test be done in my healthcare practitioner's office?
No. It requires specialized equipment and is not offered by every hospital-based laboratory. It may be necessary to send your blood sample to a reference laboratory.
If I have an HIT antibody, will it eventually go away?
The amount of antibody will generally decrease after several months, but you may develop it again if you are given heparin again due to anamnestic response.
How long is someone usually treated with heparin?
In most cases, you would be on heparin for a short period of time and then transitioned to another anticoagulant (e.g., oral Coumadin). Pregnant women who need anticoagulation may receive low molecular weight heparin (LMWH) for extended periods of time.
Should I tell all of my health practitioners that I have an HIT antibody?
Yes. This is important information for your health care practitioners to know as it may affect other procedures and some of your treatment options.
Sources Used in Current Review
Eke, s. and May, S. (2019 December 12, Updated). Heparin-Induced Thrombocytopenia. Medscape Hematology. Available online at https://emedicine.medscape.com/article/1357846-overview. Accessed September 2020.
Omer, T. et. al. (2019 Jan 8). False-Negative Platelet Factor 4 Antibodies and Serotonin Release Assay and the Utility of Repeat Testing in the Diagnosis of Heparin-Induced Thrombocytopenia and Thrombosis. Case Rep Hematol. 2019. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341253/. Accessed September 2020.
Moser, K. et. al. (2020 May, Updated). Heparin-Induced Thrombocytopenia – HIT. ARUP Consult. Available online at https://arupconsult.com/content/heparin-induced-thrombocytopenia. Accessed September 2020.
Barcellona, D. et. al. (2020 April 13). A “Catastrophic” Heparin-Induced Thrombocytopenia. Case Rep Med. 2020 Apr 13;2020:6985020. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174963/ Accessed September 2020.
(© 1995–2020). Heparin-PF4 IgG Antibody (HIT), Serum. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Overview/86533. Accessed September 2020.
Arepally, G. (2017 May 25). Heparin-induced Thrombocytopenia. Blood 2017 May 25;129(21):2864-2872. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445568/. Accessed September 2020.
Compton, F. et. al. (2019). PIFA PLUSS P4 Assay for Screening of Heparin-Induced Thrombocytopenia. Medscape from Lab Med. 2019;50(1):73-77. Available online at https://www.medscape.com/viewarticle/909646. Accessed September 2020.
Salter, B. et. al. (2016 May 31). Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review. J Am Coll Cardiol. 2016 May 31;67(21):2519-32. Available online at https://www.sciencedirect.com/science/article/pii/S0735109716324597?via%3Dihub. Accessed September 2020.
Sources Used in Previous Reviews
(© 1995-2011). Unit Code 81904: Heparin-PF4 Antibody (HIT), Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81904. Accessed September 2011.
Rodgers, III, G. and Smock, K. (Updated 2011 July). Heparin-Associated Antibody Syndrome – HIT. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/HIT.html?client_ID=LTD. Accessed September 2011.
Lefkowitz, J. (Updated 2010 July 20). Heparin-InducedThrombocytopenia. CAP from An Algorithmic Approach to Hemostasis Testing (2008) [On-line information]. Available online through http://www.cap.org. Accessed September 2011.
(© 2008). A Patient’s Guide to Antithrombotic and Thrombolytic Therapy. American College of Chest Physicians [On-line information]. Available online at http://accpstorage.org/newOrganization/patients/AT8/AT8ComprehensiveGuidePatient.pdf. Accessed September 2011.
George, J. (Revised 2009 May). Thrombocytopenia: Other Causes. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merckmanuals.com/professional/sec12/ch143/ch143f.html?qt=heparin induced&alt=sh#v971368. Accessed September 2011.
Dugdale, D. (Updated 2010 February 5). Thrombocytopenia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000586.htm. Accessed September 2011.
Dugdale, D. (Updated 2011 June 13). Thrombocytopenia – drug induced. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000556.htm. Accessed September 2011.
(2010 August 1). What Causes Thrombocytopenia? National Heart Lung and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/health-topics/topics/thcp/causes.html. Accessed September 2011.
Baroletti S. and Samuel Z. Goldhaber, S. (2006 August 22). Heparin-Induced Thrombocytopenia. American Heart Association, from Circulation 2006, 114:e355-e356 [On-line information]. PDF available for download at http://circ.ahajournals.org/content/114/8/e355.full.pdf. Accessed September 2011.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby’s Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 753-755.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 534-535.
Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007 Pp 756, 781.
(Sep 23, 2010) Eke, S. Heparin-Induced Thrombocytopenia. Medscape Reference. Available online at http://emedicine.medscape.com/article/1357846-overview#a0199. Accessed Sept. 2011.
(October 17, 2015) Eke S. Heparin-Induced Thrombocytopenia. Medscape Reference. Available online at http://emedicine.medscape.com/article/1357846-overview. Accessed February 2016.
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 1497-1499.
Lee G, Arepally G. Diagnosis and Management of Heparin-Induced Thrombocytopenia. Hematol Oncol Clin North Am. 2013 Jun; 27(3): 541–563. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668315/. Accessed February 2016.