Heparin-induced Thrombocytopenia PF4 Antibody

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) in someone who has a low platelet count (thrombocytopenia) and excessive clotting (thrombosis).

Heparin is an anticoagulant used to treat blood clots. In the body, heparin can combine with a substance call platelet factor 4 (PF4) to form a complex. Some people treated with heparin produce antibodies directed against this complex (HIT antibodies). For more on this, see the "What is being tested?" section.

A person who has HIT antibodies 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, significant thrombocytopenia, and thrombosis. The test is typically ordered along with or following a platelet count and may be followed by additional tests such as functional assays to 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 a person's serum has on the function of "normal" platelets from healthy donors.

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 a person's likelihood of having HIT II. It includes:

• The extent of thrombocytopenia (platelet decrease of 50% or more from the pre-heparin therapy level)
• The timing of the platelet count fall (typically 5-10 days after initial heparin use and within 2 day 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 a person has 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.

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 in those with a low probability of having HIT II.

The presence of HIT antibodies in someone who has been treated with heparin for 5 to 10 days, has a platelet count that has decreased by 50% or more, and has new blood clots means that it is likely the person has HIT II.

The presence of HIT antibodies in someone who has received heparin within the last 3 months and is experiencing significant thrombocytopenia within a day or two of re-starting heparin therapy may also indicate HIT II.

If HIT testing is indeterminate and confirmatory testing is positive in a person with clinical signs of HIT, then it is likely the person has HIT II.

If the test is negative for HIT antibodies,then it is unlikely that the person has HIT II. If confirmatory testing is performed and it is also negative, then it is likely that the person's symptoms are due to another cause.

The majority of people who produce HIT antibodies will not develop HIT II (i.e., have significant thrombocytopenia and thrombosis).

Many conditions and diseases other than HIT can cause thrombocytopenia by affecting 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.

Heparin-induced thrombocytopenia type I (HIT type I) may be seen in people who 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.

There are two types of heparin that may be used in 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. Once a person has developed HIT II with UFH, they are more likely to develop HIT with LMWH.

It is rare but possible for people to develop HIT antibodies, even when the only heparin that they are exposed to is the small amount used to flush out their intravenous line or catheter. 

No. It requires specialized equipment and is not offered by every hospital-based laboratory. It may be necessary to send your blood to a reference laboratory.