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Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation

  • Luca Spiezia , Elena Campello , Fabio Dalla Valle , Barry Woodhams und Paolo Simioni EMAIL logo
Veröffentlicht/Copyright: 15. August 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 55 Heft 4

Abstract

The activation of the extrinsic coagulation pathway occurs after endothelial injury when the tissue factor (TF), a transmembrane protein located outside the vasculature, binds factor VII (FVII) or activated FVII (FVIIa). Once formed, the TF-VIIa complex activates both factor IX and X and initiates the coagulation process. The TF-VIIa complex is inhibited by both TF pathway inhibitor (TFPI) and antithrombin (AT). The interaction between TF-VIIa and AT induces FVIIa-AT complex formation, which is released into the plasma. Because AT reacts with FVIIa only when it is bound to TF, the circulating levels of FVIIa-AT reflect the degree of exposure of TF to blood. Preliminary clinical studies have shown higher plasma levels of FVIIa-AT complex both in patients with a prior arterial or venous thrombotic event. Increased plasma levels of FVIIa-AT have also been reported in a number of other prothrombotic conditions – antiphospholipid antibodies, solid and hematological malignancies, pre-eclampsia (PE), obesity and cardiac surgery. However, most of the studies published so far are retrospective and with a limited sample size. Larger prospective clinical studies are needed to confirm these findings and to assess the prognostic role of this possible new biomarker for activated coagulation.

Keywords: arterial and venous thrombosis; biomarker; coagulation; FVIIa-antithrombin
Corresponding author: Paolo Simioni, MD, Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine, University of Padova, Via Giustiniani, 2-35128 Padova, Italy, Phone: (+39) 049 8212667, Fax: (+39) 049 8218731

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: Barry Woodhams used to act as a consultant for Diagnostica Stago via Haemacon Ltd.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Østerud B. Tissue factor expression in blood cells. Thromb Res 2010;125(Suppl 1):S31–4.10.1016/j.thromres.2010.01.032Suche in Google Scholar

2. Bach RR. Tissue factor encryption. Arterioscler Thromb Vasc Biol 2006;26:456–61.10.1161/01.ATV.0000202656.53964.04Suche in Google Scholar

3. Chiu J, Passam F, Butera D, Hogg PJ. Protein disulfide isomerase in thrombosis. Semin Thromb Hemost 2015;41:765–73.10.1055/s-0035-1564047Suche in Google Scholar

4. Rao LV, Nordfang O, Hoang AD, Pendurthi UR. Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity. Blood 1995;85:121–9.10.1182/blood.V85.1.121.bloodjournal851121Suche in Google Scholar

5. Jesty J, Lorenz A, Rodriguez J, Wun TC. Initiation of the tissue factor pathway of coagulation in the presence of heparin: control by antithrombin III and tissue factor pathway inhibitor. Blood 1996;87:2301–7.10.1182/blood.V87.6.2301.bloodjournal8762301Suche in Google Scholar

6. Martínez-Martínez I, Ordóñez A, Pedersen S, de la Morena-Barrio ME, Navarro-Fernández J, Kristensen SR, et al. Heparin affinity of factor VIIa: implications on the physiological inhibition by antithrombin and clearance of recombinant factor VIIa. Thromb Res 2011;127:154–60.10.1016/j.thromres.2010.11.008Suche in Google Scholar

7. Godal HC, Rygh M, Laake K. Progressive inactivation of purified factor VII by heparin and antithrombin III. Thromb Res 1974;5:773–5.10.1016/0049-3848(74)90120-0Suche in Google Scholar

8. Broze GJ Jr, Majerus PW. Purification and properties of human coagulation factor VII. J Biol Chem 1980;255:1242–7.10.1016/S0021-9258(19)86020-9Suche in Google Scholar

9. Lawson JH, Butenas S, Ribarik N, Mann KG. Complex-dependent inhibition of factor VIIa by antithrombin III and heparin. J Biol Chem 1993;268:767–70.10.1016/S0021-9258(18)53998-3Suche in Google Scholar

10. Rao LV, Rapaport SI, Hoang AD. Binding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa. Blood 1993;81:2600–7.10.1182/blood.V81.10.2600.2600Suche in Google Scholar

11. Broze GJ Jr, Likert K, Higuchi D. Inhibition of factor VIIa/tissue factor by antithrombin III and tissue factor pathway inhibitor. Blood 1993;82:1679–81.10.1182/blood.V82.5.1679.1679Suche in Google Scholar

12. Vatsyayan R, Kothari H, Mackman N, Pendurthi UR, Rao LV. Inactivation of factor VIIa by antithrombin in vitro, ex vivo and in vivo: role of tissue factor and endothelial cell protein C receptor. PLoS One 2014;9:e103505.10.1371/journal.pone.0103505Suche in Google Scholar

13. Agersø H, Brophy DF, Pelzer H, Martin EJ, Carr M, Hedner U, et al. Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following intravenous administration in hemophilia patients. J Thromb Haemost 2011;9:333–8.10.1111/j.1538-7836.2010.04152.xSuche in Google Scholar

14. Petersen LC, Karpf DM, Agersø H, Hermit MB, Pelzer H, Persson E, et al. Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin. Br J Haematol 2011;152: 99–107.10.1111/j.1365-2141.2010.08432.xSuche in Google Scholar

15. Kondo S, Kisiel W. Regulation of factor VIIa activity in plasma: evidence that antithrombin III is the sole plasma protease inhibitor of human factor VIIa. Thromb Res 1987;46:325–35.10.1016/0049-3848(87)90294-5Suche in Google Scholar

16. Hamamoto T, Kisiel W. The effect of cell surface glycosaminoglycans (GAGs) on the inactivation of factor VIIa-tissue factor activity by antithrombin III. Int J Hematol 1998;68:67–78.10.1016/S0925-5710(98)00034-6Suche in Google Scholar

17. Morrissey JH. Assay for measuring factor VIIa-antithrombin complexes. Oklaoma Medical Research Foundation, WO 03/004694, 2003.Suche in Google Scholar

18. Silveira A, Scanavini D, Boquist S, Ericsson C, Morrissey JH, Hamsten A. Elevated levels of factor VIIa-antithrombin complexes in patients with previous myocardial infarction. J Thromb Haemost 2007;5(Suppl 2):abstract P-T-010.Suche in Google Scholar

19. Smith SA, Antonaci FC, Woodhams BJ, Morrissey JH. Factor VIIa-antithrombin complexes in human plasma. J Thromb Haemost 2007;5(Suppl 2):abstract O-S-040.Suche in Google Scholar

20. Roubey RA, Lovell T, Morrissey JH. Elevated plasma levels of factor VIIa-antithrombin complexes in patients with antiphospholipid antibodies. J Thromb Haemost 2007;5(Suppl 2):abstract P-T-431.Suche in Google Scholar

21. Spiezia L, Rossetto V, Gavasso S, Tognin G, Morboeuf O, Woodhams B, et al. Decrease factor VIIa/Antithrombin complexes in 31 subjects belonging to 7 families with FVII deficiency. J Thromb Haemost 2007;5(Suppl 2):abstract P-W-087.Suche in Google Scholar

22. Spiezia L, Rossetto V, Gavasso S, Tognin G, Morboeuf O, Woodhams B, et al. Decrease factor VIIa/Antithrombin complexes in patients with venous thromboembolism: a new insight in the pathogenetic mechanism. J Thromb Haemost 2007;5(Suppl 2):abstract O-T-095.Suche in Google Scholar

23. Spiezia L, Rossetto V, Campello E, Gavasso S, Woodhams B, Tormene D, et al. Factor VIIa-antithrombin complexes in patients with arterial and venous thrombosis. Thromb Haemost 2010;103:1188–92.10.1160/TH09-08-0606Suche in Google Scholar PubMed

24. Słomka A, Świtońska M, Sinkiewicz W, Żekanowska E. Assessing circulating factor VIIa-antithrombin complexes in acute ischemic stroke: a pilot study. Clin Appl Thromb Hemost 2016. pii: 1076029616631424. [Epub ahead of print].10.1177/1076029616631424Suche in Google Scholar PubMed

25. Spiezia L, Campello E, Gentilomo C, Gavasso S, Woodhams B, Laverda AM, et al. Factor VIIa-antithrombin complexes in children with ischemic stroke. Thromb Res 2011;128:303–4.10.1016/j.thromres.2011.05.020Suche in Google Scholar PubMed

26. Silveira A, Scanavini D, Boquist S, Ericsson CG, Hellénius ML, Leander K, et al. Relationships of plasma factor VIIa-antithrombin complexes to manifest and future cardiovascular disease. Thromb Res 2012;130:221–5.10.1016/j.thromres.2011.08.029Suche in Google Scholar PubMed PubMed Central

27. Martinelli N, Girelli D, Baroni M, Guarini P, Sandri M, Lunghi B, et al. Activated factor VII–antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study. J Thromb Haemost 2016;14:655–66.10.1111/jth.13274Suche in Google Scholar

28. Schut AM, Meijers JC, Lisman-van Leeuwen Y, van Montfoort ML, Roest M, de Groot PG, et al. Decreased plasma levels of activated factor VII in patients with deep vein thrombosis. J Thromb Haemost 2015;13:1320–4.10.1111/jth.12980Suche in Google Scholar

29. Rossetto V, Spiezia L, Senzolo M, Rodriguez K, Gavasso S, Woodhams B, et al. Factor VIIa-antithrombin complexes in patients with non-neoplastic portal vein thrombosis with and without cirrhosis. Int J Lab Hematol 2013;35:101–5.10.1111/ijlh.12003Suche in Google Scholar

30. Spiezia L, Campello E, Bon M, Gavasso S, Woodhams B, Simioni P. Factor VIIa-antithrombin complexes plasma levels in cancer patients with and without thrombosis. Thromb Res 2012;129:818–9.10.1016/j.thromres.2012.02.046Suche in Google Scholar

31. Balducci D, Russo R, Vignoli A, Marchetti M, Woodhams B. Morrissey JH, et al. Activated factor VIIa-antithrombin complex (FVIIa-AT) in patients with acute promyelocytic leukemia (APL). Thromb Res 2007;120(Suppl 2):abstract PO-26.10.1016/S0049-3848(07)70179-2Suche in Google Scholar

32. Marchetti M, Tartari CJ, Russo L, Panova-Noeva M, Leuzzi A, Rambaldi A, et al. Phospholipid-dependent procoagulant activity is highly expressed by circulating microparticles in patients with essential thrombocythemia. Am J Hematol 2014;89:68–73.10.1002/ajh.23590Suche in Google Scholar

33. Campello E, Zabeo E, Radu CM, Spiezia L, Gavasso S, Fadin M, et al. Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events. Thromb Haemost 2015;113:85–96.10.1160/TH14-02-0156Suche in Google Scholar

34. Girardi G. Role of tissue factor in pregnancy complications: crosstalk between coagulation and inflammation. Thromb Res 2011;127(Suppl 3):S43–6.10.1016/S0049-3848(11)70012-3Suche in Google Scholar

35. Spiezia L, Bogana G, Campello E, Maggiolo S, Pelizzaro E, Dalle Carbonare C, et al. Whole blood thromboelastometry profiles in women with preeclampsia. Clin Chem Lab Med 2015;53:1793–8.10.1515/cclm-2014-1128Suche in Google Scholar PubMed

36. Spiezia L, Visentin S, Radu C, Bon M, Woodhams B, Cosmi E, et al. Association between increased FVIIa-antithrombin complex/FVIIa ratio and pre-eclampsia. J Matern Fetal Neonatal Med 2013;26:1352–4.10.3109/14767058.2013.784265Suche in Google Scholar PubMed

37. Davidson SJ, Woodhams B. Factor VIIa-antithrombin complexes during cardiac surgery using cardiopulmonary bypass. Int J Lab Hematol 2011;33:614–6.10.1111/j.1751-553X.2011.01331.xSuche in Google Scholar PubMed

38. Simioni P, Spiezia L. Factor VIIa-AT complex plasma levels and arterial thrombosis. Thromb Res 2012;130:141.10.1016/j.thromres.2011.09.020Suche in Google Scholar PubMed

Received: 2016-5-5
Accepted: 2016-7-12
Published Online: 2016-8-15
Published in Print: 2017-3-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

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  2. Editorial
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https://doi.org/10.1515/cclm-2016-0399
Schlagwörter für diesen Artikel
arterial and venous thrombosis; biomarker; coagulation; FVIIa-antithrombin

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. The central role of external quality assurance in harmonisation and standardisation for laboratory medicine
  4. Review
  5. Fecal calprotectin in inflammatory bowel diseases: update and perspectives
  6. Mini Review
  7. Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation
  8. Opinion Papers
  9. Improving quality in the preanalytical phase through innovation, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE)
  10. Metabolite profiling can change health-care delivery to obese patients with fatty liver disease: the search for biomarkers
  11. Genetics and Molecular Diagnostics
  12. Rapid screening for targeted genetic variants via high-resolution melting curve analysis
  13. Evaluation of the new cobas® HCV genotyping test based on real-time PCRs of three different HCV genome regions
  14. General Clinical Chemistry and Laboratory Medicine
  15. Harmonisation of serum dihydrotestosterone analysis: establishment of an external quality assurance program
  16. Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years’ experience
  17. Peer groups splitting in Croatian EQA scheme: a trade-off between homogeneity and sample size number
  18. Prevalence of pseudonatremia in a clinical laboratory – role of the water content
  19. Retrospective validation of a β-trace protein interpretation algorithm for the diagnosis of cerebrospinal fluid leakage
  20. Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a Chinese hospital system perspective
  21. Performance evaluation of ImmunoCAP® ISAC 112: a multi-site study
  22. Clinical autoantibody detection by microarray
  23. Cardiovascular Diseases
  24. Kinetics of troponin I in patients with myocardial injury after noncardiac surgery
  25. Infectious Diseases
  26. P35 and P22 Toxoplasma gondii antigens abbreviate regions to diagnose acquired toxoplasmosis during pregnancy: toward single-sample assays
  27. Letters to the Editor
  28. Deciphering a macro-troponin I complex; a case report
  29. Interference of laboratory disinfection with trichloro-isocyanuric acid on cardiac troponin I measurement using the Vitros immunoassay system
  30. Massive interference in free T4 and free T3 assays misleading clinical judgment
  31. In defense of aldosterone measurement by immunoassay: a broader perspective
  32. The prevalence of hemolysis – a survey using hemolysis index
  33. Detection of BRAFV600K mutant tumor-derived DNA in the pleural effusion from a patient with metastatic melanoma
  34. Evaluation of the accuracy of the Greiner Bio-One FC Mix Glucose tube
  35. Congress Abstracts
  36. 4th EFLM-BD European Conference on Preanalytical Phase Amsterdam (NL), 24–25 March 2017
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