Association of Thrombin-Activatable Fibrinolysis Inhibitor with Acute Pulmonary Embolism

Abstract

Background Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and high levels may have an association with thrombosis. The aim of the current study was to investigate the association of TAFI antigen levels with pulmonary thromboembolism (PTE).

Patients and Methods A case–control study was conducted with 29 patients with PTE and 17 age- and gender-matched control individuals. Plasma levels of TAFI were measured at the time of diagnosis, then at 3 and 6 months after the event.

Results Initial TAFI levels (%) were higher in patients with PTE than in the control group (190,0 [65,0–250,0] vs 133,0 [83,0–153,0]; p = 0.003). TAFI levels significantly decreased at the third and sixth months after initial diagnosis (p < 0.05). The percentage reductions in TAFI levels were 12 and 36.8% at 3 and 6 months, respectively. The Odss ratio (OR) of TAFI level for PTE was found to be 1.024 (95% CI: 1.007–1.040; p = 0.005). There was no significant correlation of initial TAFI levels with age, gender, smoking status, history of thrombosis, pulmonary artery pressure, and D-dimer levels (p > 0.05). In the sixth month of treatment, patients with residual thrombosis were seen to have similar baseline levels and reductions of TAFI as patients without residual thrombosis (p > 0.05).

Conclusion The result of this study suggests that high TAFI levels may have a role in the occurrence of PTE without impact on treatment outcome.

Keywords

TAFI - pulmonary thromboembolism - association

Publikationsverlauf

Eingereicht: 05. September 2020

Angenommen: 04. März 2021

Artikel online veröffentlicht:
17. Juni 2021

• References

• 1 Rosovsky R, Zhao K, Sista A, Rivera-Lebron B, Kabrhel C. Pulmonary embolism response teams: purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost 2019; 3 (03) 315-330
• 2 Willemse JL, Heylen E, Nesheim ME, Hendriks DF. Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy?. J Thromb Haemost 2009; 7 (12) 1962-1971
• 3 Lisman T. Decreased plasma fibrinolytic potential as a risk for venous and arterial thrombosis. Semin Thromb Hemost 2017; 43 (02) 178-184
• 4 Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activatable fibrinolysis inhibitor. J Biol Chem 1995; 270 (24) 14477-14484
• 5 Marx PF. Thrombin-activatable fibrinolysis inhibitor. Curr Med Chem 2004; 11 (17) 2335-2348
• 6 Bavbek N, Ceri M, Akdeniz D. et al. Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients. Ren Fail 2014; 36 (05) 743-747
• 7 Mosnier LO, Buijtenhuijs P, Marx PF, Meijers JC, Bouma BN. Identification of thrombin activatable fibrinolysis inhibitor (TAFI) in human platelets. Blood 2003; 101 (12) 4844-4846
• 8 van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood 2000; 95 (09) 2855-2859
• 9 Meltzer ME, Lisman T, de Groot PG. et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116 (01) 113-121
• 10 Schroeder V, Kucher N, Kohler HP. Role of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with acute pulmonary embolism. J Thromb Haemost 2003; 1 (03) 492-493
• 11 Radu CM, Spiezia L, Campello E, Gavasso S, Woodhams B, Simioni P. Thrombin activatable fibrinolysis inhibitor in cancer patients with and without venous thromboembolism. Thromb Res 2013; 132 (04) 484-486
• 12 Libourel EJ, Bank I, Meinardi JR. et al. Co-segregation of thrombophilic disorders in factor V Leiden carriers; the contributions of factor VIII, factor XI, thrombin activatable fibrinolysis inhibitor and lipoprotein(a) to the absolute risk of venous thromboembolism. Haematologica 2002; 87 (10) 1068-1073
• 13 Silveira A, Schatteman K, Goossens F. et al. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease. Thromb Haemost 2000; 84 (03) 364-368
• 14 Leenaerts D, Bosmans JM, van der Veken P, Sim Y, Lambeir AM, Hendriks D. Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction. J Thromb Haemost 2015; 13 (12) 2227-2232
• 15 Bridge KI, Bollen L, Zhong J. et al. Thrombin-activatable fibrinolysis inhibitor in human abdominal aortic aneurysm disease. J Thromb Haemost 2017; 15 (11) 2218-2225
• 16 Donmez A, Aksu K, Aydin H. et al. The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet disease and their association with thrombosis. Thromb Res 2010; 126 (03) 207-210
• 17 Erdogan M, Solmaz S, Canataroglu A. et al. Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in diabetic foot ulcers. Endocrine 2010; 37 (03) 449-454
• 18 Eser M, Kement M, Balin S. et al. Is there any role of thrombin activatable fibrinolysis inhibitor in the development of a hypercoagulable state in gastric cancer. World J Surg Oncol 2012; 10: 180
• 19 Grosso G, Vikerfors A, Woodhams B. et al. Thrombin activatable fibrinolysis inhibitor (TAFI)—a possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res 2017; 158 (158) 168-173
• 20 Yaoita N, Satoh K, Satoh T. et al. Thrombin-activatable fibrinolysis inhibitor in chronic thromboembolic pulmonary hypertension. Arterioscler Thromb Vasc Biol 2016; 36 (06) 1293-1301
• 21 Zidane M, de Visser MC, ten Wolde M. et al. Frequency of the TAFI-438 G/A and factor XIIIA Val34Leu polymorphisms in patients with objectively proven pulmonary embolism. Thromb Haemost 2003; 90 (03) 439-445
• 22 Brouwers GJ, Vos HL, Leebeek FW. et al. A novel, possibly functional, single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor (TAFI) gene is also associated with TAFI levels. Blood 2001; 98 (06) 1992-1993
• 23 Declerck PJ. Thrombin activatable fibrinolysis inhibitor. Hamostaseologie 2011; 31 (03) 165-166 , 168–173
• 24 Denorme F, Wyseure T, Peeters M. et al. Inhibition of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 reduces ischemic brain damage in mice. Stroke 2016; 47 (09) 2419-2422
• 25 Zhou J, Kochan J, Yin O. et al. A first-in-human study of DS-1040, an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor, in healthy subjects. J Thromb Haemost 2017; 15 (05) 961-971