Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy. HIT is characterized by a 30–50% decrease in platelet count and an increased thrombotic risk due to platelet activation. Without treatment, up to 50% of patients can experience thrombotic events.

How Does HIT Occur?

When a person is given heparin, the drug can combine with a substance found in platelets, called platelet factor 4 (PF4), and form a complex. In some patients, the heparin-PF4 complex triggers an immune response, which results in production of an antibody that binds to the heparin-PF4 complex. When the antibodies bind to the heparin-PF4 complex on the surface of platelets, the platelets activate, leading to a decrease in platelet count and an increased risk of thrombosis. Activated platelets release additional PF4, propagating the cycle.

Seroconversion occurs five to 10 days after heparin therapy is initiated and results in increased risk of serious complications from blood clots.

Possible complications of HIT include the following:

  • Deep-vein thrombosis, pulmonary emboli
  • Myocardial infarction, stroke
  • Compromised blood flow to limbs
  • Skin necrosis, end-organ damage
  • Death

Serotonin Release Assay Features and Benefits

  • Gold-standard confirmatory test
  • Complex, highly sensitive and specific functional assay that uses high-performance liquid chromatography (HPLC) to measure serotonin released when platelets are activated by HIT antibodies
  • Measures heparin-dependent platelet activation
  • Medical director review and consultation available

Method Description

ARUP performs the serotonin release assay (SRA) by using washed donor platelets incubated with patient sera and low (therapeutic) and high (supratherapeutic) concentrations of heparin. In the presence of low (therapeutic) heparin concentrations, HIT-positive sera result in platelet activation and platelet granule release. The platelet granules contain serotonin; thus, serotonin serves as a surrogate marker for platelet activation. Any serotonin released from the donor platelets is identified and quantified by high-performance liquid chromatography (HPLC). Adding supratherapeutic amounts of heparin suppresses a positive response and improves specificity of the SRA by demonstrating that the platelet activation is heparin dependent. The results are expressed as percent release (amount of serotonin released/total amount of platelet serotonin) at low and high heparin concentrations.


A prompt diagnosis is critical for patient management.

Two types of assays are available, functional assays and enzyme-linked immunosorbent assays (ELISAs).

Functional Assays ELISAs

SRAs are highly specific, functional assays that detect whether antibodies formed in response to heparin/PF4 complexes activate platelets in the presence of heparin

ELISA assays are sensitive for HIT antibody detection but have poor specificity for clinical HIT, given that they are incapable of determining if the antibodies have platelet-activating properties


Patients who have undergone orthopedic and cardiac bypass surgical procedures develop HIT syndrome more frequently than patients receiving medical or obstetric care.

Laboratory Testing

ARUP Test Codes and Names


Serotonin Release Assay (Heparin Dependent Platelet Antibody), Unfractionated Heparin


Heparin-Induced Thrombocytopenia (HIT) PF4 Antibody, IgG with Reflex to Serotonin Release Assay (Heparin Dependent Platelet Antibody), Unfractionated Heparin


Heparin-Induced Thrombocytopenia (HIT) PF4 Antibody, IgG

Related ARUP Consult Topic

Heparin-Induced Thrombocytopenia - HIT

For additional information, please call ARUP Client Services at 800-522-2787 and mention keyword: HIT.