Test Id : AATTF
Antithrombin Activity, with Reflex to Antithrombin Antigen, Plasma
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosis of antithrombin deficiency, acquired or congenital
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| AATTA | Antithrombin Summary Interp | No | No |
| ATTI | Antithrombin Antigen, P | Yes | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If the activity is abnormal low, then the summary interpretation and antigen will be performed at an additional charge.
Method Name
A short description of the method used to perform the test
Chromogenic Assay
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
Aliases
Lists additional common names for a test, as an aid in searching
Anti-Thrombin III
Antithrombin Activity
AT III Activity/Functional
AT3 Activity/Functional
SeanAtlasTest
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If the activity is abnormal low, then the summary interpretation and antigen will be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Plasma Na Cit
Ordering Guidance
Coagulation testing is highly complex, often requiring the performance of multiple assays and correlation with clinical information. For that reason, consider ordering AATHR / Thrombophilia Profile, Plasma and Whole Blood.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.
2. Centrifuge, transfer all plasma into a plastic vial, and centrifuge plasma again.
3. Aliquot plasma into a plastic vial leaving 0.25 mL in the bottom of centrifuged vial.
4. Freeze plasma immediately (no longer than 4 hours after collection) at -20 degrees C or ideally, at or below -40 degrees C.
Additional Information:
1. A 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.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
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. The minimum volume is sufficient for one attempt at testing.
0.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | 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 |
|---|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosis of antithrombin deficiency, acquired or congenital
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If the activity is abnormal low, then the summary interpretation and antigen will be performed at an additional charge.
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 the anticoagulant activity of antithrombins (approximately 1000-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 anticoagulant activity of heparin.
The antithrombin gene on chromosome 1 encodes a glycoprotein with a molecular weight of approximately 58,000 D, which is synthesized in the liver and is present in a relatively high plasma concentration (approximately 2.3 mcmol/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 and pulmonary embolism) with the potential of development as early as adolescence or younger adulthood. More than 100 different alterations 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 1:2000 to 1:3000 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% of individuals have antithrombin deficiency. Among the recognized hereditary thrombophilic disorders (including deficiencies of proteins C and S, as well as activated protein C -resistance [factor V Leiden variant]), 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 disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF) 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.
Normal values:
80%-130%
Normal, full-term newborn infants have lower levels (> or =35%-40%) that reach normal values by 90 days of age. Premature infants (30-36 weeks gestation) have lower levels that reach normal values by 180 days of age.
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 of 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, see GNANT / Antithrombin Deficiency, SERPINC1 Gene, Next-Generation Sequencing, Varies.
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 is of unknown hemostatic significance. Direct factor Xa inhibitors, rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) may falsely elevate the antithrombin activity and mask a diagnosis of antithrombin deficiency.
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
-Bilirubin >40 mg/dL
-Triglycerides >2300 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
Recommendations for in-depth reading of a clinical nature
1. Lane DA, Olds RJ, Thein SL. Antithrombin and its deficiency. In: Bloom AL, Forbes CD, Thomas DP, eds. Haemostasis and Thrombosis. 3rd ed. Churchill Livingstone; 1994:655-670
2. Lane DA, Bayston T, Olds RJ, et al. Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haesmostasis. Thromb Haemost. 1997;77(1):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(1):66-69. doi: 10.1002/(sici)1096-8652(199901)60:1<66:aid-ajh11>3.0.co;2-d
4. Mammen EF. Antithrombin: its physiological importance and role in DIC. Semin Thromb Haemost. 1998;24(1):19-25. doi: 10.1055/s-2007-995819
5. Yohe S, Olson J. Thrombophilia: Assays and Interpretation. In: Kottke-Marchant Wiley K, ed. Laboratory Hematology Practice. Blackwell Publishing; 2012:492-508
6. Van Cott EM, Orlando C, Moore GW, et al. Recommendations for clinical laboratory testing for antithrombin deficiency; Communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(1):17-22. doi:10.1111/jth.14648
Method Description
Describes how the test is performed and provides a method-specific reference
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 N-alpha-benzyloxycarbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride and subsequently releases p-nitroaniline (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.(Package insert: HemosIL Liquid Antithrombin. Instrumentation Laboratory Comp; 06/2017)
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.
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
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
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 has been modified from the manufacturer's instructions. Its performance characteristics were 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.
CPT codes are provided by the performing laboratory.
85300
85301
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 |
|---|---|---|
| AATTF | Antithrombin Activity, w/ Reflex, P | 27811-9 |
| 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.
|
|---|---|---|
| AATTF | Antithrombin Activity, w/ Reflex, P | 27811-9 |