Test Catalog

Test Id : SRAU

Serotonin Release Assay, Unfractionated Heparin, Mass Spectrometry, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detecting heparin-dependent platelet activating antibodies implicated in the pathogenesis of heparin-induced thrombocytopenia


This test can be used to assess for the presence of heparin-induced thrombocytopenia antibodies, which may develop after unfractionated or low molecular weight heparin therapy.

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Serotonin Release Assay, UFH, MS, S

Lists additional common names for a test, as an aid in searching




Specimen Type
Describes the specimen type validated for testing

Serum Red

Shipping Instructions

Specimen should be frozen if shipped or stored for longer than 48 hours.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation:

1. Specimen should be collected from a fasting (preferred, but not required) patient during an episode of suspected heparin induced thrombocytopenia.

2. Patient should not be on ticagrelor (Brilinta) as this may interfere with the assay, yielding a false-negative result.

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Collection Container/Tube: Red top (serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. After collection, specimen should sit at ambient temperature for a minimum of 1 hour in order to clot completely.

2. Centrifuge and aliquot serum into a plastic vial.

Specimen Stability Information: Frozen (preferred) 2 years/Refrigerate 7 days


If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross lipemia  Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Red Frozen (preferred)
Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detecting heparin-dependent platelet activating antibodies implicated in the pathogenesis of heparin-induced thrombocytopenia

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

There are established and emerging disorders that are collectively termed thrombocytopenia and thrombosis syndromes. The most commonly recognized is heparin-induced thrombocytopenia (HIT); additional newer associations include adenovirus vector-based SARS-CoV-2 vaccine-induced thrombocytopenia and HIT-like syndromes that occur in the absence of exposure to heparin (currently termed spontaneous or autoimmune HIT). In this situation, the heparin platelet-factor 4 (PF4) IgG antibody typically develops after surgery or infection. HIT is a serious immune-mediated syndrome, (ie, type II HIT or immune HIT), which occurs in 1% to 5% of patients treated with unfractionated heparin and at a lower frequency in patients treated with low-molecular weight heparin.


The 4Ts score is a validated scoring system to estimate the pretest clinical probability of HIT. Scores are assigned to the degree and timing of onset of thrombocytopenia, presence or absence of thrombosis (arterial venous), in the absence of other potential explanations for the thrombocytopenia. In HIT, typical onset of thrombocytopenia is between days 5 and 10 of heparin therapy, but thrombocytopenia can arise earlier (<5 days after heparin exposure ie, rapid onset of HIT) or later (>4 weeks after heparin exposure ie, delayed onset of HIT). The platelet count typically decreases by 40% to 50% from baseline or the postoperative peak (in surgical patients), even though the absolute count may remain normal, and thrombocytopenia resolves within 7 to 14 days of cessation of heparin therapy (unless there is another coexisting cause of thrombocytopenia). Development or progression of (venous or arterial) thrombosis is termed heparin-induced thrombocytopenia with thrombosis syndrome and can occur in 30% to 50% of patients, rarely even following discontinuation of heparin therapy.


Other syndromes of thrombocytopenia and thrombosis:

There are an increasing number of reports of patients who develop thrombocytopenia and thrombosis after surgery, particularly after orthopedic surgery and after selected infections. The clinical course and laboratory characteristics of this group of patients are similar to the classical HIT occurring with heparin exposure except perhaps development of high-titer antibodies against heparin/PF4 complexes. An emerging recognition is the development of thrombocytopenia and thrombosis occurring 3 to 4 weeks after adenovirus vector SARS-CoV-2 exposure. The clinical course is also similar to immune HIT.


Laboratory characteristics of heparin-induced thrombocytopenia:

HIT is caused, in at least 90% of cases, by antibodies to antigen complexes of heparinoid (heparin or similar glycosaminoglycans) and platelet factor 4 (PF4). PF4 is a platelet-specific heparin-binding (neutralizing) protein that is abundant in platelet alpha granules from which it is secreted following platelet stimulation. A reservoir of PF4 normally accumulates on vascular endothelium. Following heparin administration, immunogenic complexes of PF4 and heparin can provide an antigenic stimulus for antibody development in some patients. Antibodies bound to platelets that display complexes of PF4/heparin antigen can activate platelets via interaction of the Fc immunoglobulin tail of the IgG antibody with platelet Fc gamma IIa receptors, leading to perpetuation of the pathologic process that can cause platelet-rich thrombi in the microcirculation in some cases.


Functional assays for HIT antibody detection rely on antibody-mediated heparin-dependent platelet activation. The endpoint of platelet activation may be platelet aggregation or platelet secretion of serotonin or adenosine triphosphate using patient serum or plasma supplemented with heparin and platelets from carefully normal selected donors. The sensitivity of functional assays for HIT ranges from 50% to 60% for heparin-dependent platelet aggregation assays to 70% to 80% for serotonin release assays. The specificity of positive functional tests for HIT diagnosis is believed to be high (> or =90%). However, because of their complexity, functional tests for detecting HIT antibodies are not widely available.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Low Heparin Serotonin Release:


High Heparin Serotonin Release:


Serotonin Release Assay Result:


Provides information to assist in interpretation of the test results

In a negative serotonin release assay (SRA), patient serum induced serotonin release of below 20% from normal donor platelets in presence of low concentration of unfractionated heparin (UFH) (0.1U/mL) regardless of the serotonin release with high concentration of UFH (100 U/mL).


In a positive SRA, patient serum induced serotonin release of 20% or more from normal donor platelets in presence of low concentration of UFH (0.1U/mL). This release is inhibited in presence of high concentration of UFH (100 U/mL) and falls below 20%.


In an indeterminate SRA, patient serum induced serotonin release of 20% or more from normal donor platelets in presence of low concentration of UFH (0.1U/mL) and high concentration of UFH (100 U/mL). Indeterminate results can occur due to non-heparin dependent antibodies (eg, human leukocyte antigen antibodies). Occasionally some indeterminate results may show greater than 50% inhibition of serotonin release from normal donor platelets in presence of high concentration of UFH (100U/mL) compared to low concentration of UFH (0.1U/mL) which is suggestive for heparin induced thrombocytopenia in the right clinical context.


Low heparin release %

High heparin release %






> or =20%


> or =20%



Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Ticagrelor use by the patient may result in a false-negative serotonin release assay (SRA) result.


A negative SRA result makes the diagnosis of HIT less likely, however, SRA negative patients with bonafide clinical HIT in whom the SRA result may turn positive on subsequent testing have been reported in the literature.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Warkentin TE, Arnold DM, Nazi I, Kelton JG: The platelet serotonin-release assay. Am J Hemtol. 2015 Jun;90(6):564-572. doi: 10.1002/ajh.24006

2. Minet V, Dogne JM, Mullier F: Functional assays in the diagnosis of heparin-induced thrombocytopenia: a review. Molecules. 2017 Apr;22(4):617. doi: 10.3390/molecules22040617

3. Sono-Koree NK, Crist RA, Frank EL, et al: A high-performance liquid chromatography method for the serotonin release assay is equivalent to the radioactive method. Int. J Lab Hematol. 2016 Feb;38(1):72–80. doi: 10.1111/ijlh.12442

Method Description
Describes how the test is performed and provides a method-specific reference

Patient serum is incubated with donor platelets and different concentrations of heparin. Anti-heparin platelet-factor 4/heparin antibodies present in the patient serum will bind to platelet Fc gamma receptors and activate donor platelets, releasing serotonin from the platelet granules. The released serotonin is measured utilizing liquid chromatography -tandem mass spectrometry.(Carling RS, Degg TS, Allen KR, et al: Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem. 2002;39:577-582)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

7 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test


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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
SRAU Serotonin Release Assay, UFH, MS, S 50736-8
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
616230 Low Heparin Serotonin Release 50728-5
616231 High Heparin Serotonin Release 50727-7
616232 Serotonin Release Assay Result 66488-8
616233 Interpretation 50733-5
616234 Comment 77202-0
616235 Disclaimer 62364-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
New Test 2022-07-26
New Test 2022-06-16