Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the peritoneal fluid in patients with peritonitis – is the key towards intraperitoneal adhesions and complications?

Zbigniew Ziętek


Introduction: The concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the peritoneal fluid and blood plasma in patients with peritonitis were examined. The fibrinogenesis of the peritoneal cavity is not well-known although it is regarded as the main cause of intraperitoneal adhesions and the complications that arise from this.
Materials and methods: The study enrolled a group of 77 consecutive patients with peritonitis, 28 women and 49 men aged 18–79 years (with an average age of 45 ±18 years). The patients were divided into 2 subgroups: those with complications (n = 64) and those without (n = 13). Concentrations of TF and TFPI in the peritoneal fluid and blood plasma of patients were examined.
Results: In the peritoneal fluid, patients with complications had a higher concentration of TF (p < 0.007), but a lower concentration of TFPI (p < 0.0006). In blood plasma, TF was higher but TFPI was lower (p < 0.00001 in both). The area under curve (AUC) for TF and TFPI was 0.763 and 0.93 respectively, the cut-off point was 809.08 pg/mL and 21.6 pg/mL, respectively. The positive predictive value (PPV) and negative predictive value (NPV) for TF was 68% and 75% and for TFPI, 80% and 85%, respectively.
Conclusions: The data can be taken as an example of cross-linking between extravascular coagulation and intraperitoneal adhesions. On the basis of TF and TFPI, it is clearly illustrated that there is some connection between coagulation and peritoneal fibrinogenesis, which could be involved in the pathogenesis of many complications in abdominal surgery and also indicate therapeutic targets.


peritoneal adhesions; fibrinogenesis; peritoneal fluid; peritonitis; complications

Full Text:



van Goor H, Bom VJ, van der Meer J, Sluiter WJ, Bleichrodt RP. Coagulation and fibrinolytic responses of human peritoneal fluid and plasma to bacterial peritonitis. Br J Surg 1996;83(8):1133-5.

Weijer S, Schoenmakers SHHF, Florquin S, Levi M, Vlasuk GP, Rote WE, et al. Inhibition of the Tissue Factor/Factor VIIa Pathway Does Not Influence the Inflammatory or Antibacterial Response to Abdominal Sepsis Induced by Escherichia coli in Mice. J Infect Dis 2004;189:2308-17.

Pawlinski R, Mackman N. Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsis. Crit Care Med 2004;32(5 Suppl):S293-7.

Hoefs J, Barnes T, Halle P. Intraperitoneal coagulation in chronic liver disease ascites. Dig Dis Sci 1981;26(6):518-22.

Henderson JM, Stein SF, Kutner M, Wiles MB, Ansley JD, Rudman D. Analysis of Twenty-three plasma proteins in ascites. The depletion of fibrinogen and plasminogen. Ann Surg 1980;192(6):738-42.

Agarwal S, Joyner KA Jr, Swaim MW. Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease. Am J Gastroenterol 2000;95(11):3218-24.

Koca YS, Tarhan ÖR, Kaya S, Gökçe Ceylan B. Effects of saline lavage temperature on peritoneal fibrinolysis and adhesion formation. Ulus Travma Acil Cerrahi Derg 2016;22(1):1-6.

Aarons CB, Cohen PA, Gower A, Reed KL, Leeman SE, Stucchi AF, et al. Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity. Ann Surg 2007;245(2):176-84.

Lakbakbi S, Debrumetz A, Rieu P, Nguyen P. Human Neutrophils Support Thrombin Generation in Peritonitis. Perit Dial Int 2015;35(5):599-602.

Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 2002;99(3):1053-9.

van Veen SQ, Levi M, van Vliet AK, Florquin S, van Gulik TM, Boermeester MA.

Peritoneal lavage with activated protein C alters compartmentalized coagulation and fibrinolysis and improves survival in polymicrobial peritonitis. Crit Care Med 2006;34(11):2799-805.

Ray NF, Denton WG, Thamer M, Henderson SC, Perry S. Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994.

J Am Coll Surg 1998;186(1):1-9.

Dijkstra FR, Nieuwenhuijzen M, Reijnen MM, van Goor H. Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions. Scan J Gastroenterol 2000;232:52-9.

Dobbie JW. Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 1992;12(1):14-27.

Parhami-Seren B, Butenas S, Krudysz-Amblo J, Mann KG. Immunologic quantitation of tissue factors. J Thromb Haemost 2006;4(8):1747-55.

Witkowski M, Landmesser U, Rauch U. Tissue factor as a link between inflammation and coagulation. Trends Cardiovasc Med 2016;26(4):297-303.

Camerota AJ, Creasey AA, Patla V, Larkin VA, Fink MP. Delayed Treatment with Recombinant Human Tissue Factor Pathway Inhibitor Improves Survival in Rabbits with Gram-Negative Peritonitis. J Infect Dis 1998;177(3):668-76.

Culp WTN, Holt DE. Septic peritonitis. Compend Contin Educ Vet 2010;32(10):E1-14.

Haslinger B, Kleemann R, Toet KH, Kooistra T. Simvastatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-α–activated human peritoneal mesothelial cells. Kidney Int 2003;63:2065-74.

Schirm S, Liu X, Jennings LL, Jedrzejewski P, Dai Y, Hardy S. Fragmented Tissue Factor Pathway Inhibitor (TFPI) and TFPI C‐Terminal Peptides Eliminate Serum‐Resistant Escherichia coli from Blood Cultures. J Infect Dis 2009;199(12):1807-15.

Mutsaers SE, Birnie K, Lansley S, Herrick SE, Lim CB, Prêle CM. Mesothelial cells in tissue repair and fibrosis. Front Pharmacol 2015;6:113. doi: 10.3389/fphar.2015.00113.

Bajaj MS, Pendurthi U, Koenig K, Pueblitz S, Idell S. Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells. Eur Respir J 2000;15(6):1069-78.

Buyne OR, van Goor H, Bleichrodt RP, Verweij PE, Hendriks T. Both tissue-type plasminogen activator and urokinase prevent intraabdominal abscess formation after surgical treatment of peritonitis in the rat. Surgery 2008;144(1):66-73.

Isaza-Restrepo A, Martin-Saavedra JS, Velez-Leal JL, Vargas-Barato F, Riveros-Duenas R. The Peritoneum: Beyond the Tissue – A Review. Front Physiol 2018;9:738-745. doi: 10.3389/fphys.2018.00738.

Yung S, Li FK, Chan TM. Peritoneal mesothelial cell culture and biology. Perit Dial Int 2006;26(2):162-73.

Macarak EJ, Lotto CE, Koganti D, Jin X, Wermuth PJ, Olsson AK, et al. Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal adhesion formation. J Surg Res 2018;227:198-210.

Sitter T, Gödde M, Spannagl M, Fricke H, Kooistra T. Intraperitoneal coagulation and fibrinolysis during inflammation: In vivo and in vitro observations. Fibrinolysis 1996;10:99-104.

Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol 2011;17(411):4545-53.

Brinkmann T, Schmidt M, Prohaska W, Kleesiek K. Tissue Factor Pathway Inhibitor (TFPI): Biochemistry, Genetics, and Implications for Thrombophilia. J Lab Med 2001;25(7-8):269-76.

Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012;34(1):43-62.

Takasugi Y, Shiokawa Y, Kajikawa R, Oh J, Yamamoto Y, Sakata I, et al. Mesenteric venous thrombosis in a patient with congenital afibrinogenemia and diffuse peritonitis. Ann Hematol 2005;84(2):129-30.

van Veen SQ, Cheung CW, Meijers JC, van Gulik TM, Boermeester MA. Anticoagulant and anti-inflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis. J Thromb Haemost 2006;4(11):2343-51.

Fareed J, Callas DD, Hoppensteadt D, Bermes EW Jr. Tissue factor antigen levels in various biological fluids. Blood Coagul Fibrinolysis 1995;6 Suppl 1:S32-6.

Hariharan D, Wilkes EA, Aithal GP, Travis SJ, Lobo DN. Spontaneous central venous thrombosis and shunt occlusion following peritoneovenous shunt placement for intractable ascites. Ann R Coll Surg Engl 2017;99(5):e145-e147.

Thaler J, Hell L, Schwabl P, Wisgrill L, Ay C, Quehenberger P, et al. Intraperitoneal Activation of Blood Coagulation via Tissue Factor Exposing Extracellular Vesicles in Patients with Liver Disease and Ascites. Hamostaseologie 2019;39:S1-S92.

Goldfarb RD, Glock D, Johnson K, Creasey AA, Carr C, McCarthy RJ, et al. Randomized, blinded, placebo-controlled trial of tissue factor pathway inhibitor in porcine septic shock. Shock 1998;10(4):258-64.

Abraham E, Reinhart K, Opal S, Demeyer I, Doig Ch, Rodriguez AL,

et al. Efficacy and Safety of Tifacogin (Recombinant Tissue Factor Pathway Inhibitor) in Severe Sepsis: a randomized controlled trial. JAMA 2003;290(2):238-47. doi: 10.1001/jama.290.2.238.

Opal SM, Palardy JBA, Parejo NBA, Creasey AA. The activity of tissue factor pathway inhibitor in experimental models of superantigen-induced shock and polymicrobial intra-abdominal sepsis. Crit Care Med 2001;29(1):13-7.

Matyal R, Vin Y, Delude R, Lee C, Creasey A, Fink M. Extremely low doses of tissue factor pathway inhibitor decrease mortality in a rabbit model of septic shock. Intensive Care Med 2001;27:1274-80.

DOI: https://doi.org/10.21164/pomjlifesci.744

Copyright (c) 2021 Zbigniew Ziętek

License URL: https://creativecommons.org/licenses/by-nc-nd/3.0/pl/