Test Details
Methodology
TAT is measured by enzyme immunoassay using a sandwich technique. The patient sample containing TAT is incubated with antibodies against thrombin, and the unbound constituents are removed by washing. Enzyme conjugated antibodies to antithrombin are then added to the reaction, and the excess antibodies are removed by washing. The remaining (bound) enzymatic activity acts upon a chromophore and color development is proportional to the TAT in the sample.
Result Turnaround Time
3 - 9 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
Use
This test is used to assess thrombin formation and antithrombin consumption.
Limitations
Improper collection of the sample or insufficient mixing of the sample and anticoagulant in the collection tube can lead to falsely elevated TAT values.
Custom Additional Information
Upon activation of coagulation, antithrombin complexes with thrombin as well as other serine proteases (antithrombin, TAT) and serves as a surrogate measure for thrombin level in the blood that is more easily detected than readily degradable thrombin.1-5 Thrombin-antithrombin (TAT) complex formation is greatly enhanced by the presence of heparin or other glycosaminoglycans. This reaction initially is reversible but becomes irreversible following the formation of a covalent bond between antithrombin and thrombin. TAT complex formation results in complete inhibition of thrombin's activity.6 TAT is considered to be a biomarker of coagulation activation whose formation indicates entrance into a prothrombotic state.
Elevated levels of TAT have been associated with pregnancy,2 stroke,1,2,3,6-9 septicemia,10 myocardial infarction,11-14 malignancy,15-21 liver disease,22,23 sepsis24 and other predisposing causes of thrombosis. Increased levels are also reported during anticoagulant therapy.25,26 The TAT test has been suggested as a sensitive parameter for predicting future VTE.27-32 Decreasing TAT levels can also indicate the resolution of a thrombotic event. Rises in TAT concentrations have been observed in the course of heparin and fibrinolysis therapy.
Specimen Requirements
Specimen
Plasma, frozen
Volume
2 mL
Minimum Volume
1 mL (Note: This volume does not allow for repeat testing.)
Container
Blue-top (sodium citrate) tube
Collection Instructions
Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.33 Evacuated collection tubes must be filled to completion to ensure a proper blood-to-anticoagulant ratio.34,35 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples unless the sample is collected using a winged (butterfly) collection system. With a winged blood collection set, a discard tube should be drawn first to account for the dead space of the tubing and prevent under-filling of the evacuated tube.36,37 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternative anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes.
Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.
Stability Requirements
| Temperature | Period |
|---|---|
| Room temperature | 4 hours |
| Refrigerated | 4 hours |
| Freeze/thaw cycles | Stable x5 |
Reference Range
0.0–4.2 ng/dL
Storage Instructions
Freeze; five freeze/thaw cycles are acceptable. Stable at room temperature or refrigerated for four hours.
Patient Preparation
Do not draw from an arm with a heparin lock or heparinized catheter.
Footnotes
1. Lundbech M, Krag AE, Christensen TD, Hvas AM. Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients. Thromb Res. 2020 Feb;186:80-85. PubMed 31918352
2. López Y, Paloma MJ, Rifón J, Cuesta B, Páramo JA. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res. 1999 Jan 15;93(2):71-78. PubMed 9950260
3. Lippi G, Cervellin G, Franchini M, Favaloro EJ. Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future. J Thromb Thrombolysis. 2010 Nov;30(4):459-471. PubMed 20213258
4. Blickstein I. Thrombophilia and women's health: An overview. Obstet Gynecol Clin North Am. 2006 Sep;33(3):347-356. PubMed 16962913
5. Ota S, Wada H, Abe Y, et al. Elevated levels of prothrombin fragment 1 + 2 indicate high risk of thrombosis. Clin Appl Thromb Hemost. 2008 Jul;14(3):279-285. PubMed 18160575
6. Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol. 2007 May;62(2):126-136. PubMed 17293122
7. Dati F, Pelzer H, Wagner C. Relevance of markers of hemostasis activation in obstetrics/gynecology and pediatrics. Semin Thromb Hemost. 1998;24(5):443-448. PubMed 9834011
8. Catov JM, Bodnar LM, Hackney D, Roberts JM. Simhan HN. Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth. Obstet Gynecol. 2008 Nov;112(5):1116-1122. PubMed 18978114
9. Schjetlein R, Haugen G, Wisløff F. Markers of intravascular coagulation and fibrinolysis in preeclampsia: association with intrauterine growth retardation. Acta Obstet Gynecol Scand. 1997 Jul;76(6):541-546. PubMed 9246959
10. Li Y, Li H, Wang Y, Guo J, Zhang D. Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy. Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231195089. PubMed 37605466
11. Reganon E, Vila V, Martinez-Sales V, Vaya A, Aznar J. Inflammation, fibrinogen and thrombin generation in patients with previous myocardial infarction. Haematologica. 2002 Jul;87(7):740–5 discussion 745. PubMed 12091125
12. Bernardo-Castro S, Sousa JA, Brás A, et al. Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Front Neurol. 2020 Dec 9;11:594672. PubMed 33362697
13. Song P, Xie J, Li W, Zhang X, Sun Z, You C. Effect of plasma thrombin-antithrombin complex on ischemic stroke: a systematic review and meta-analysis. Syst Rev. 2023 Feb 14;12(1):17. PubMed 36788633
14. Wu CH, Yang RL, Huang SY, et al. Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal. Eur J Neurol. 2011 Aug;18(8):1060-1066. PubMed 21244583
15. Sierko E, Sobierska M, Zabrocka E, et al. Endothelial Microparticles and Blood Coagulation Activation in Head and Neck Cancer Patients Undergoing Radiotherapy or Radiochemotherapy. In Vivo. 2019 Mar-Apr;33(2):627-632. PubMed 30804151
16. Kitayama H, Kondo T, Sugiyama J, et al. Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study. BMC Cancer. 2017 May 19;17(1):351. PubMed 28525975
17. Kovacs MJ, Davies GA, Chapman JA, et al. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY. 10. Br J Haematol. 2015 Feb;168(4):511-517. PubMed 25302852
18. Ay C, Dunkler D, Simanek R, et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol. 2011May 20;(15):2099-2103. PubMed 21464402
19. Fidan E, Kavgaci H, Orem A, et al. Thrombin activatable fibrinolysis inhibitor and thrombin-antithrombin-III-complex levels in patients with gastric cancer. Tumour Biol. 2012 Oct;33(5):1519-1525. PubMed 22535370
20. Goldenberg N, Kahn SR, Solymoss S. Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism. J Clin Oncol. 2003 Nov 15;21(22):4194-4199. PubMed 14615447
21. Iversen LH, Thorlacius-Ussing O. Relationship of coagulation test abnormalities to tumour burden and postoperative DVT in resected colorectal cancer. Thromb Haemost. 2002 Mar;87(3):402-408. PubMed 11916070
22. Elvers FL, Stamouli M, Adelmeijer J, et al. In vivo generation of thrombin in patients with liver disease without apparent evidence of activation of the intrinsic or extrinsic pathway of coagulation. J Thromb Haemost. 2023;21(8):2078-2088. PubMed 36990155
23. Kerr R, Newsome P, Germain L, et al. Effects of acute liver injury on blood coagulation. J Thromb Haemost. 2003 Apr;1(4):754-759. PubMed 12871412
24. Koyama K, Madoiwa S, Nunomiya S, et al. Combination of thrombin-antithrombin complex, plasminogen activatorinhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study. Crit Care. 2014 Jan 13;18(1):R13. PubMed 24410881
25. McFarland CP, Lind SE. Thrombin Generation Biomarkers Decline With Parenteral Anticoagulation-An Overlooked Means of Anticoagulation Monitoring? Clin Appl Thromb Hemost. 2018 Jul;24(5):708-717. PubMed 29439639
26. Walker CP, Royston D. Thrombin generation and its inhibition: a review of the scientific basis and mechanism of action of anticoagulant therapies. Br J Anaesth. 2002 Jun;88(6):848-863. PubMed 12173205
27. Lin Z, Sun H, Li D, et al. Thrombin antithrombin complex concentration as an early predictor of deep vein thrombosis after total hip arthroplasty and total knee arthroplasty. BMC Musculoskelet Disord. 2022 Jun 14;23(1):574. PubMed 35701797
28. Kobayashi H, Akamatsu Y, Kumagai K, et al. The use of factor Xa inhibitors following opening-wedge high tibial osteotomy for venous thromboembolism prophylaxis. Knee Surg Sports Traumatol Arthrosc. 2017 Sep;25(9):2929-2535. PubMed 27000391
29. De Prost D, Ollivier V, Vie P, Benacerraf R, Duparc J, Khoury A. D-dimer and thrombin antithrombin III complex levels uncorrelated with phlebographic findings in 11 total knee replacement patients. Ann Biol Clin (Paris). 1990;48:235-238. PubMed 2193559
30. Ginsberg JS, Brill-Edwards P, Panju A, et al. Pre-operative plasma levels of thrombin-antithrombin III complexes correlate with the development of venous thrombosis after major hip or knee surgery. Thromb Haemost. 1995 Aug;74:602-605. PubMed 8584991
31. Carmassi F, Morale M, de Negri F, et al. Thrombin antithrombin III complexes as an additional diagnostic aid in pulmonary embolism. Haemostasis. 1996 Jan-Feb;26(1):16-22. PubMed 8698274
32. Cofrancesco E, Cortellaro M, Corradi A, Ravasi F, Bertocchi F. Coagulation activation markers in the prediction of venous thrombosis after elective hip surgery. Thromb Haemost. 1997 Feb;77:267-269. PubMed 9157579
33. Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin Pathol. 1997 Jan;107(1):105-110. PubMed 8980376
34. Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant. Am J Clin Pathol. 1998 Jun;109(6):754-757. PubMed 9620035
35. National Committee for Clinical Laboratory Standardization. Collection, Transport, and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline. 5th ed. Villanova, Pa: NCCLS; 2008. Document H21-A5:28(5).
36. Gottfried EL, Adachi MM. Prothrombin time and activated partial thromboplastin time can be performed on the first tube. Am J Clin Pathol. 1997 Jun;107(6):681-683. PubMed 9169665
37. McGlasson DL, More L, Best HA, Norris WL, Doe RH, Ray H. Drawing specimens for coagulation testing: Is a second tube necessary? Clin Lab Sci. 1999 May-Jun;12(3):137-139. PubMed 10539100
LOINC® Map
| Order Code | Order Code Name | Order Loinc | Result Code | Result Code Name | UofM | Result LOINC |
|---|---|---|---|---|---|---|
| 015045 | Thrombin-Antithrombin Complex | 14182-0 | 015046 | Thrombin-Antithrombin Complex | ng/dL | 14182-0 |
| Order Code | 015045 | |||||
| Order Code Name | Thrombin-Antithrombin Complex | |||||
| Order Loinc | 14182-0 | |||||
| Result Code | 015046 | |||||
| Result Code Name | Thrombin-Antithrombin Complex | |||||
| UofM | ng/dL | |||||
| Result LOINC | 14182-0 |