Test Details
Methodology
Prothrombin fragment 1+2 (F1+2) is measured by an enzyme immunoassay based on the sandwich principle.6 F 1+2 in the sample binds to anti-F 1+2 antibodies fixed to the microtiter plate during an incubation period. Peroxidase conjugated antibodies are then added and a second incubation takes place. A chromophore is added and color formation is directly proportional to the concentration of F 1+2.
Result Turnaround Time
5 - 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 for evaluation of F 1+2 in plasma as a determinant of in vivo thrombin generation.
Limitations
Improper collection of the sample or insufficient mixing of the sample and anticoagulant in the collection tube can lead to falsely elevated F1+2 values.
As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes.
Custom Additional Information
Prothrombin fragment 1+2 (F1+2) is generated as a byproduct of the in vivo cleavage of prothrombin into thrombin by membrane-bound prothrombinase (a complex of factor Xa and factor Va).1-4 F1+2 has been measured as a marker of thrombin generation and hence of coagulation activation.1,3,5 Its biological half-life is 90 minutes, so it persists in blood for several hours after formation.1,3,5 This relatively long presence in plasma makes it more reliable for measuring ongoing coagulation than other markers.1,3
F1+2 has been studied as a potential marker of thrombotic risk in numerous conditions.6 F1+2 levels are increased in pregnancy7,8 and in women treated with ethinylestradiol-containing birth control pills.9 Elevated levels have also been reported in patients with antiphospholipid syndrome,10,11 protein C deficiency12 and protein S deficiency13 and asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations.14 Levels of F1+2 have been reported to be elevated in venous thromboembolism,6,15 acute coronary syndromes,8,16 stroke,10,17 atrial fibrillation18 and peripheral arterial disease.19-21 Recent studies have reported in elevated F1+2 levels in COVID-19.22,23 F1+2 has been studied as a prothrombotic marker in a number of cancers.8,24-32 Anticoagulants have been found to reduce F1+2 levels.33-35
Specimen Requirements
Specimen
Plasma, frozen
Volume
1 mL
Minimum Volume
0.5 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.36 Evacuated collection tubes must be filled to completion to ensure a proper blood-to-anticoagulant ratio.37,38 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.39,40 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.
Reference Range
69–229 pmol/L
Storage Instructions
Freeze.
Patient Preparation
Do not draw from an arm with a heparin lock or heparinized catheter.
Causes for Rejection
Gross hemolysis; clotted specimen; frozen specimen thawed in transit; improper labeling; improper collection tube
Footnotes
1. Páramo JA. Prothrombin fragments in cardiovascular disease. Adv Clin Chem. 2010;51:1-23. PubMed 20857616
2. Krishnaswamy S. The transition of prothrombin to thrombin. J Thromb Haemost. 2013 Jun;11 Suppl 1(0 1):265-276. PubMed 23809130
3. Merlini PA, Ardissino D. Laboratory Measurement of Thrombin Activity--What Every Clinician Scientist Needs to Know. J Thromb Thrombolysis. 1995;2(2):85-92. PubMed 10608009
4. Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: Insights gained from studies using markers of hemostatic system activation. Blood. 1987 Aug;70(2):343-350. PubMed 3607275
5. 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
6. 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
7. Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-130. PubMed 12709915
8. López Y, Paloma MJ, Rifón J, Cuesta B, Páramo J. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res. 1999 Jan 15;93(2):71-78. PubMed 9950260
9. Douxfils J, Morimont L, Bouvy C. Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk. Semin Thromb Hemost. 2020 Nov;46(8):872-886. PubMed 33080636
10. Ellis MH, Kesler A, Friedman Z, Drucker I, Radnai Y, Kott E. Value of prothrombin fragment 1.2 (F 1.2) in the diagnosis of stroke in young patients with antiphospholipid antibodies. Clin Appl Thromb Hemost. 2000 Apr;6(2):61-64. PubMed 10775022
11. Zangari M, Lockwood CJ, Scher J, Rand JH. Prothrombin activation fragment (F1.2) is increased in pregnant patients with antiphospholipid antibodies. Thromb Res. 1997 Feb 1;85(3):177-183. PubMed 9058492
12. Bauer KA, Broekmans AW, Bertina RM, et al. Hemostatic enzyme generation in the blood of patients with hereditary protein C deficiency. Blood. 1988 May;71(5):1418-1426. PubMed 2965928
13. Zöller B, Holm J, Svensson P, Dahlbäck B. Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency. Thromb Haemost. 1996 Feb;75(2):270-274. PubMed 8815575
14. Bauer KA, Humphries S, Smillie B, et al. Prothrombin activation is increased among asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations. Thromb Haemost. 2000 Sep;84(3):396-400. PubMed 11019961
15. Wexels F, Seljeflot I, Pripp AH, Dahl OE. D-dimer and prothrombin fragment 1 + 2 in urine and plasma in patients with clinically suspected venous thromboembolism. Blood Coagul Fibrinolysis. 2016 Jun;27(4):396-400. PubMed 26595215
16. Hansen CH, Ritschel V, Halvorsen S, et al. Markers of thrombin generation are associated with myocardial necrosis and left ventricular impairment in patients with ST-elevation myocardial infarction. Thromb J. 2015 Sep 22;13:31. PubMed 26396552
17. 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
18. Negreva M, Prodanova K, Zarkova A. Paroxysmal Atrial Fibrillation: An Independent Risk Factor for Prothrombotic Conditions. J Atr Fibrillation. 2020 Aug 31;13(2):2297. PubMed 34950291
19. Arfan S, Zamzam A, Syed MH, et al. The Clinical Utility of D-Dimer and Prothrombin Fragment (F1+2) for Peripheral Artery Disease: A Prospective Study. Biomedicines. 2022 Apr 11;10(4):878. PubMed 35453628
20. Zamzam A, Syed MH, Rand ML, et al. Altered coagulation profile in peripheral artery disease patients. Vascular. 2020 Aug;28(4):368-377. PubMed 32252612
21. Mota AP, de Castro Santos MER, das Chagas Lima e Silva F, et al. Hypercoagulability markers in patients with peripheral arterial disease: association to ankle-brachial index. Angiology. 2009 Oct-Nov;60(5):529-535. PubMed 19015166
22. Al-Samkari H, Song F, Van Cott EM, Kuter DJ, Rosovsky R. Evaluation of the prothrombin fragment 1.2 in patients with coronavirus disease 2019 (COVID-19). Am J Hematol. 2020 Dec;95(12):1479-1485. PubMed 32780525
23. Ranucci M, Sitzia C, Baryshnikova E, et al. Covid-19-Associated Coagulopathy: Biomarkers of Thrombin Generation and Fibrinolysis Leading the Outcome. J Clin Med. 2020 Oct 28;9(11):3487. PubMed 33126772
24. 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. PubMed 31918352
25. Pépin M, Kleinjan A, Hajage D, et al. ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer. J Thromb Haemost. 2016 Feb 14;14(2):306-315. PubMed 26589836
26. Dickmann B, Ahlbrecht J, Ay C, et al. Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study. Haematologica. 2013;98(8):1309-1314. PubMed 23585523
27. 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
28. Kohli M, Fink LM, Spencer HJ, Zent CS. Advanced prostate cancer activates coagulation: a controlled study of activation markers of coagulation in ambulatory patients with localized and advanced prostate cancer. Blood Coagul Fibrinolysis. 2002 Jan;13(1):1-5. PubMed 11994561
29. Hanzal E, Tatra G. Prothrombin fragment F 1 + 2 plasma concentrations in patients with gynecologic malignancies. Gynecol Oncol. 1993 Jun;49(3):373-376. PubMed 8314540
30. Seitz R, Rappe N, Kraus M, et al. Activation of oagulation and fibrinolysis in patients with lung cancer: relation to tumour stage and prognosis. Blood Coagul Fibrinolysis. 1993 Apr;4(2):249-254. PubMed 8388741
31. Ay C, Vormittag R, Dunkler D, et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol. 2009 Sep 1;27(25):4124-4129. PubMed 19636003
32. Sallah S, Husain A, Sigounas V, et al. Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy. Clin Cancer Res. 2004 Nov 1;10(21):7238-7243. PubMed 15534097
33. 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
34. Páramo JA. Prothrombin fragments in cardiovascular disease. Adv Clin Chem. 2010;51:1-23. PubMed 20857616
35. Conway EM, Bauer KA, Barzegar S, Rosenberg RD. Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diathesis. J Clin Invest. 1987 Dec;80(6):1535-1544. PubMed 3680513
36. 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
37. 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
38. 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).
39. 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
40. 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 |
|---|---|---|---|---|---|---|
| 117230 | Prothrombin Fragment 1+2 | 117231 | Prothrombin Fragment 1+2 | pmol/L | 25742-8 | |
| Order Code | 117230 | |||||
| Order Code Name | Prothrombin Fragment 1+2 | |||||
| Order Loinc | ||||||
| Result Code | 117231 | |||||
| Result Code Name | Prothrombin Fragment 1+2 | |||||
| UofM | pmol/L | |||||
| Result LOINC | 25742-8 |