Mehmet ERDOĞAN, Kemal ÜRETEN, Mustafa ÖZBEK, Erdem AKBAL

Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in acromegaly patients in remission

Background/aim: Acromegaly is associated with increased morbidity andmortality, mostly due to cardiovascular complications. Plasmathrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels are associated with coagulation/fibrinolysis and inflammation. PlasmaTAFI may play a role in arterial thrombosis in cardiovascular diseases. In this study, it was aimed to evaluate the thrombin-activatablefibrinolysis inhibitor (TAFI) antigen and homocysteine levels in patients with acromegaly and healthy control subjects.Materials and methods: Plasma TAFI antigen and homocysteine levels in 29 consecutive patients with acromegaly and 26 age-matchedhealthy control subjects were measured. All patients included in the study were in remission. The TAFIa/ai antigen in the plasmasamples was measured using a commercially available ELISA kit.Results: Routine biochemical parameters, fasting blood glucose, prolactin, thyroid stimulating hormone, total-cholesterol, low densitylipoprotein cholesterol, triglyceride, and homocysteine levels were similar in the 2 groups (P > 0.05), whereas the plasma TAFI antigenlevels were significantly elevated in the acromegalic patients (154.7 ± 94.0%) when compared with the control subjects (107.2 ± 61.6%)(P = 0.033). No significant correlation was identified by Pearson’s correlation test between the plasma TAFI antigen and homocysteinelevels (r = 0.320, P = 0.250).Conclusion: A significant alteration in the plasma TAFI antigen levels was detected in acromegaly. Increased plasma TAFI antigen levelsmight aggravate prothrombotic and thrombotic events in patients with acromegaly.

PDF

___

1. Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S et al. Long term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. Journal of Clinical Endocrinology and Metabolism 1998; 83 (10): 3419-3426.
2. Bates AS, Van’t Hoff W, Jones JM, Clayton RN. An audit of outcome of treatment in acromegaly. Quarterly Journal of Medicine 1993; 86 (5): 293-299.
3. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews 2004; 25 (1): 102-152.
4. Clayton RN. Cardiovascular Function in Acromegaly. Endocrine Reviews 2003; 24 (3): 272-277.
5. van Thiel W, Bax JJ, Biermasz NR, Holman ER, Poldermans D et al. Persistent diastolic dysfunction despite successful long-term octreotide treatment in acromegaly. European Journal of Endocrinology 2005; 153: 231-238.
6. Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D. Isolation, molecular cloning and partial characterization of a novel carboxypeptidase B from human plasma. Journal of Biological Chemistry 1991; 266: 21833-21838.
7. Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activatable fibrinolysis inhibitor. Journal of Biological Chemistry 1995; 270: 14477-14484.
8. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI dependent. Blood 1996; 88: 2093-3100.
9. Bajzar L. Thrombin activatable fibrinolysis inhibitor and an antifibrinolytic pathway. Arteriosclerosis Thrombosis and Vascular Biology 2000; 20: 2511-2518.
10. Sakharov D, Plow EF, Rijken DJ. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B. Journal of Biological Chemistry 1997; 272: 14477-14482.
11. Kruszynska YT, Yu JG, Olefsky JM, Sobel BE. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes 2000; 49 (4): 633-639.
12. Hori Y, Gabazza EC, Yano Y, Katsuki A, Suzuki K et al. Insulin resistance is associated with increased circulating levels of thrombin-activatable fibrinolysis inhibitor in type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism 2002; 87: 660-665.
13. Aubert H, Frere C, Aillaud MF, Morange PE, Juhan-Vague I et al. Weak and nonindependent association between plasma TAFI antigen levels and the insulin resistance syndrome. Journal of Thrombosis and Haemostasis 2003; 1: 791-797.
14. Genoud V, Quintana PG, Gionco S, Baldessari A, Quintana I. Structural changes of fibrinogen molecule mediated by the N-homocysteinylation reaction. Journal of Thrombosis and Haemostasis 2018; 45 (1): 66-76. doi: 10.1007/s11239-017- 1574-1.
15. Reyes-Vidal C, Fernandez JC, Bruce JN, Crisman C, Conwell IM et al. Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. Journal of Clinical Endocrinology and Metabolism 2014; 99 (11): 4124-32. doi: 10.1210/jc.2014-2259
16. Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH et al. Acromegaly: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2014; 99 (11): 3933-3951. doi: 10.1210/jc.2014-2700.
17. Albarel F, Castinetti F, Morange I, Guibert N, Graillon T et al. Pre-surgical medical treatment, a major prognostic factor for long-term remission in acromegaly. Pituitary 2018; 21 (6): 615-623. doi: 10.1007/s11102-018-0916-0.
18. AACE Acromegaly Guidelines Task Force. AACE Medical Guidelines for Clinical Practice for the diagnosis and treatment ofacromegaly. Endocrine Practice 2004; 10: 213-225.
19. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM et al. Growth hormone and pituitary radiotherapy, but notserum insulin-like growth factor-concentrations, predict excess mortality in patients with acromegaly. Journal of Clinical Endocrinology and Metabolism 2004; 89: 1613-1617.
20. Kirilov G, Zacharieva S, Alexandrov AS, Lozanov V, Mitev V. Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: a comparison with plasma homocysteine. Methods and Findings in Experimental and Clinical Pharmacology 2009; 31 (7): 457- 461. doi: 10.1358/mf.2009.31.7.1406701.
21. Hekimsoy Z, Ozmen B, Ulusoy S. Homocysteine levels in acromegaly patients. Neuro Endocrinology Letters 2005; 26 (6): 811-814.
22. Montaner J, Ribo M, Monasterio J, Molina CA, Alvarez-Sabin J. Thrombin-activable fibrinolysis inhibitor levels in the acute phase of ischemic stroke. Stroke 2003; 34 (4): 1038-1040.
23. Silveira A, Schatteman K, Goossens F, Moor E, Scharpé S et al. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease. Thrombosis and Haemostasis 2000; 84: 364-368.
24. A. Santamaria A, Martinez-Rubio M, Borrell J, Mateo R. Ortin et al. Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level. Haematologica 2004; 89: 880-881.
25. Paola Cellai A, Antonucci E, Alessandrello Liotta A, Fedi S, Marcucci R et al. TAFI activity and antigen plasma levels are not increased in acute coronary artery disease patients admitted to a coronary care unit. Thrombosis Research 2006; 118 (4): 495-500.
26. Santamaria A, Martinez-Rubio A, Borrell M, Mateo J, Ortin R et al. Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level. Haematologica 2004; 89 (7): 880-881.
27. Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ et al. Menstrual cycle irregularity and risk for future cardiovascular disease. Journal of Clinical Endocrinology and Metabolism 2002; 87 (5): 2013-2017.
28. Oral B, Mermi B, Dilek M, Alanoğlu G, Sütçü R. Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with polycystic ovary syndrome. Gynecological Endocrinology 2009; 25 (2): 110-116. doi: 10.1080/09513590802549874.
29. Erem C, Ucuncu O, Yilmaz M, Kocak M, Nuhoglu I et al. Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hypothyroidism. Endocrine 2009; 35 (1): 75-80. doi: 10.1007/ s12020-008-9116-4.
30. Erem C, Nuhoglu I, Kocak M, Yilmaz M, Sipahi ST et al. Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI. Endocrine 2008; 33: 270-276. doi: 10.1007/s12020-008-9088-4.