Heparin-induced Thrombocytopenia PF4 Antibody
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?
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. For more details, read the article on Low Platelets.
What is HIT type I and how does it differ from HIT type II?
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.
Can the heparin-induced thrombocytopenia (HIT) antibody test be done in my healthcare practitioner's office?
If I have an HIT antibody, will it eventually go away?
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 healthcare practitioners that I have an HIT antibody?