Test ID: ATTF
Antithrombin Activity, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Diagnosis of antithrombin deficiency, acquired or congenital
Monitoring treatment of antithrombin deficiency disorders, including infusion of antithrombin therapeutic concentrate
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Chromogenic Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
AT3 Activity/Functional
AT III Activity/Functional
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
See Coagulation Studies in Special Instructions.
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Spin down, remove plasma, and spin plasma again.
2. Freeze specimen immediately at < or =-40 degrees C, if possible.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. Each coagulation assay requested should have its own vial.
3. Heparin treatment may lower plasma antithrombin.
4. Coagulation testing is highly complex, often requiring the performance of multiple assays and correlation with clinical information. For that reason, we suggest ordering THRMP/83093 Coagulation Consultation, Thrombosis/Hypercoagulability, Blood and Plasma.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Antithrombin is a member of the serine protease inhibitor (serpin) superfamily. It is the principal plasma anticoagulant serpin mediating inactivation of serine protease procoagulant enzymes, chiefly thrombin and coagulation factors Xa and IXa.(1) Heparin and certain other naturally occurring glycosaminoglycans markedly enhance antithrombin's anticoagulant activity (approximately 1,000-fold) by providing a template to catalyze formation of covalently bonded, inactive complexes of serine protease and antithrombin that are subsequently cleared from circulation. Antithrombin is the mediator of heparin's anticoagulant activity.
The antithrombin gene on chromosome 1 encodes a glycoprotein of approximately 58,000 molecular weight that is synthesized in the liver and is present in a relatively high plasma concentration (approximately 2.3 umol/L). The biological half-life of antithrombin is 2 to 3 days.
Hereditary antithrombin deficiency, a relatively rare autosomal dominant disorder, produces a thrombotic diathesis (thrombophilia). Individuals with hereditary antithrombin deficiency are usually heterozygous with plasma antithrombin activity results of approximately 40% to 70%. These patients primarily manifest with venous thromboembolism (deep vein thrombosis [DVT] and pulmonary embolism [PE]) with the potential of development as early as adolescence or younger adulthood. More than 100 different mutations have been identified throughout the gene producing either the more common type I defects (low antithrombin activity and antigen) or the rarer type II defects (dysfunctional protein with low activity and normal antigen).(2) Homozygous antithrombin deficiency appears to be incompatible with life.
The incidence of hereditary antithrombin deficiency is approximately 1:2,000 to 1:3,000 in general populations, although minor deficiency (antithrombin activity = 70%-75%) may be more frequent (approximately 1:350-650). In populations with venous thrombophilia, approximately 1% to 2% have antithrombin deficiency. Among the recognized hereditary thrombophilic disorders (including deficiencies of proteins C and S, as well as activated protein C [APC]-resistance [factor V Leiden mutation]), antithrombin deficiency may have the highest phenotypic penetrance (greater risk of venous thromboembolism). Arterial thrombosis (eg, stroke, myocardial infarction) has occasionally been reported in association with hereditary antithrombin deficiency.
Hereditary deficiency of antithrombin activity can also occur because of defective glycosylation of this protein in individuals with carbohydrate-deficient glycoprotein syndromes (CDGS).(3) Antithrombin activity assessment may be useful as an adjunct in the diagnosis and management of CDGS.
Acquired deficiency of antithrombin is much more common than hereditary deficiency. Acquired deficiency can occur due to:
-Heparin therapy (catalysis of antithrombin consumption)
-Intravascular coagulation and fibrinolysis (ICF) or disseminated intravascular coagulation (DIC), and other consumptive coagulopathies
-Liver disease (decreased synthesis and/or increased consumption) or with nephritic syndrome (urinary protein loss)
-L-asparaginase chemotherapy (decreased synthesis)
-Other conditions (1)
In general, the clinical implications (thrombotic risk) of antithrombin deficiency in these disorders are not well defined, although antithrombin replacement in severe DIC/IFC is being evaluated.(4) Assay of antithrombin activity may be of diagnostic or prognostic value in some acquired deficiency states.
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.
> or =6 months-adults: 80-130%
Normal, full-term newborn infants may have decreased levels (> or =35-40%), which reach adult levels by 90 days postnatal.*
Healthy, premature infants (30-36 weeks gestation) may have decreased levels which reach adult levels by 180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Interpretation Provides information to assist in interpretation of the test results
Antithrombin deficiencies due to inherited causes are much less common than those due to acquired causes (see Clinical Information). Diagnosis or hereditary deficiency requires clinical correlation, with the prospect of repeat testing (including antithrombin antigen assay) and family studies (with appropriate counseling). DNA-based diagnostic testing may be helpful, but is not readily available.
The clinical significance (thrombotic risk) of acquired antithrombin deficiency is not well established, but accumulating information suggests possible benefit of antithrombin replacement therapy in carefully selected situations.(4)
Antithrombin deficiency, acquired or congenital, may contribute to the phenomenon of "heparin therapy resistance" (requirement of larger heparin doses than expected for achievement of therapeutic anticoagulation responses). However, it may more often have other pathophysiology, such as "acute-phase" elevation of coagulation factor VIII or plasma heparin-binding proteins.
Increased antithrombin activity has no definite clinical significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Antithrombin functional result is affected by:
-Heparin (unfractionated or low-molecular-weight) >4 U/mL
-Alpha(1)-antitrypsin >4 mg/mL
-Alpha(2)-macroglobulin >10 mg/mL
-Heparin cofactor II >4 U/mL
-Hemoglobin >500 mg/dL
-Billrubin >40 mg/dL
-Triglycerides >2,300 mg/dL
Heparin therapy may temporarily decrease plasma antithrombin activity into the abnormal range.
Antithrombin activity in serum specimens may be significantly lower than in plasma.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Lane DA, Olds RJ, Thein SL: Antithrombin and its deficiency. In Haemostasis and Thrombosis. 3rd edition. Edited by AL Bloom, CD Forbes, DP Thomas, et al: London, England, Churchill Livingstone, 1994, pp 655-670
2. Lane DA, Bayston T, Olds RJ, et al: Antithrombin mutation database: For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haesmostasis. Second (1997) update Thromb Haemost 1997;77:197-211
3. Young G, Dricsoll MC: Coagulation abnormalities in the carbohydrate-deficient glycoprotein syndrome: case report and review of the literature. Am J Hematol 1999;60:66-69
4. Mammen EF: Antithrombin: its physiological importance and role in DIC. Semin Thromb Haemost 1998;24:19-25
Method Description Describes how the test is performed and provides a method-specific reference
This assay is performed on the Beckman Coulter ACL TOP. Patient plasma, containing antithrombin, is mixed and incubated with reagent containing factor Xa and excess heparin. Factor Xa activity in the reagent is rapidly inhibited by antithrombin. Residual factor Xa activity is then measured using an amidolytic activity assay. This occurs when residual factor Xa lyses chromogenic substrate S-2765 (N-a-Z-D-Arg-Gly-Arg-pNA 2HCI) and subsequently releases pNA (detected at 405 nm) in a level that is inversely proportional to the amount of antithrombin in the sample. This method is based on inhibition of factor Xa and, therefore, only higher amounts of heparin cofactor II, alpha-2-macroglobulin, or alpha-1-antitrypsin will influence the assay. (Demers C, Henderson P, Blajchman MA, et al: An antithrombin III assay based on Factor Xa inhibition provides a more reliable test to identify congenital antithrombin III deficiency than an assay based on thrombin inhibition. Thromb Haemost 1993;69:231-235 Bohner J, von Pape KW, Laurock M: Thrombin-based antithrombin assays show overestimation of antithrombin III activity in patients on heparin therapy due to heparin cofactor II influence. Thromb Haemost 1994;71:280-283)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
85300
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| ATTF | Antithrombin Activity, P | 27811-9 |
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