Increased Tissue Factor Pathway Inhibitor (TFPI) and Coagulation in Patients with Insulin-dependent Diabetes mellitus

Paul B Leurs; Rene van Oerle; Bruce H R Wolffenbuttel; Karly Hamulyak

doi:10.1055/s-0038-1655991

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1997; 77(03): 472-476
DOI: 10.1055/s-0038-1655991

Clinical Studies

Schattauer GmbH Stuttgart

Increased Tissue Factor Pathway Inhibitor (TFPI) and Coagulation in Patients with Insulin-dependent Diabetes mellitus

Paul B Leurs

The Department of Internal Medicine, Division of Endocrinology and Metabolism, and Division of Hematology, University Hospital, Maastricht, The Netherlands

,

Rene van Oerle

The Department of Internal Medicine, Division of Endocrinology and Metabolism, and Division of Hematology, University Hospital, Maastricht, The Netherlands

,

Bruce H R Wolffenbuttel

The Department of Internal Medicine, Division of Endocrinology and Metabolism, and Division of Hematology, University Hospital, Maastricht, The Netherlands

,

Karly Hamulyak

The Department of Internal Medicine, Division of Endocrinology and Metabolism, and Division of Hematology, University Hospital, Maastricht, The Netherlands

› Institutsangaben

Abstract

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Summary

Recently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F₁₊₂ fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F₁₊₂ levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F₁₊₂ and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F₁₊₂ levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F₁₊₂ (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F₁₊₂ levels and ETP.

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Referenzen

References
1 Stern DM, Esposito C, Gerlach H, Gerlach M, Ryan J, Handley D, Nawroth P. Endothelium and regulation of coagulation. Diab Care 1991; 14 (Suppl. 01) 160-166
2 Bourin M, Lindahl U. Glycosaminoglycans and the regulation of blood coagulation. Biochem J 1993; 289: 313-330
3 Ostermann H, van de Loo J. Factors of the hemostatic system in diabetic patients. A survey of controlled studies. Haemostasis 1986; 16: 386-416
4 Carmassi F, Morale M, Puccetti R, De Negri F, Monzani F, Navalesi R, Mariani G. Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. Thromb Res 1992; 67: 643-654
5 Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T. Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vase Biol 1995; 15: 1114-11120
6 Maiello M, Boeri D, Podesta F, Cagliero E, Vichi M, Odetti P, Adezati L, Lorenzi M. Increased expression of tissue plasminogen activator and its inhibitor and reduced fibrinolytic potential of human endothelial cells cultured in elevated glucose. Diabetes 1992; 41: 1009-1015
7 Pelzer H, Schwarz A, Stiiber W. Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 1991; 65: 153-159
8 Hemker HC, Wielders S, Kessels H, Béguin S. Continuous registration of thrombin generation in plasma, its use for determination of the thrombin potential. Thromb Haemost 1993; 70: 617-624
9 Broze GJ, Miletich JP. Characterization of the inhibition of tissue factor in serum. Blood 1987; 69: 150-155
10 Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP. Cultured normal human hepatocytes do not synthesize liporpotein-associated coagulation inhibitor:evidence that endothelium is the principal site of its synthesis. Proc Natl Acad Sci USA 1990; 87: 8869-8873
11 Lindahl AK, Sandset PM, Abildgaard U. The present status of tissue factor pathway inhibitor. Blood Coagul Fibrinol 1992; 3: 439-449
12 Valentin S, Lamkjoer A, Østergaard P, Ilum Nielsen J, Nordfang O. Characterization of the binding between tissue factor pathway inhibitor and glycosaminoglycans. Thromb Res 1994; 75: 173-183
13 Sandset PM, Simes PA, Abildgaard U. Factor VII and extrinsic pathway inhibitor in acute coronary disease. Br J Haematol 1989; 72: 391-396
14 Moor E, Hamsten A, Karpe F, Båvenholm P, Blombäck M. Silveira A:Relationship of tissue pathway inhibitor activity to plasma lipoproteins and myocardial infarction at a young age. Thromb Haemost 1994; 71: 707-712
15 Kario K, Matsuo T, Yamada T, Matsuo M. Increased tissue factor pathway inhibitor levels in uremic patients on regular hemodialysis. Thromb Haemost 1994; 71: 275-279
16 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic pathway inhibitor (EPI). Thromb Res 1988; 50: 803-813
17 Jensen T. Increased plasma concentration of von Willebrand factor in insulin dependent diabetics with incipient nephropathy. Br Med J 1989; 298: 27-28
18 Iwashima Y, Sato T, Watanabe K, Ooshima E, Hiraishi S, Ishii H, Kazama M, Makino I. Elevation of plasma thrombomodulin level in diabetic patients with early diabetic nephropathy. Diabetes 1990; 39: 983-988
19 Collier A, Rumley A, Rumley AG, Paterson JR, Leach JP, Lowe GDO, Small M. Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. Diabetes 1992; 41: 909-913
20 Myrup B, Rossing P, Jensen T, Gram J, Kluft C, Jespersen J. Procoagulant activity and intimal dysfunction in IDDM. Diabetologia 1995; 38: 73-78
21 Leurs PB, van OerleR, Hamulyak K, Wolffenbuttel BHR. Tissue factor pathway inhibitor in patients with IDDM. Diabetes 1995; 44: 80-84
22 Ellis D, Coonrod BA, Dorman JS, Kelsey SF, Becker DJ, Avner ED, Orchard TJ. Choice of urine sample predictive of microalbuminuria in patients with insulin-dependent diabetes mellitus. Am J Kidney Dis 1989; 13: 321-328
23 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400
24 Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activity velocity in whole plasma independent of thrombin decay processes. Thromb Haemost 1986; 56: 9-17
25 Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 1989; 32: 219-226
26 Stehouwer CDA, Zellenrath P, Polak BCP, Baarsma GS, Nauta JJP, Donker AJM, den Ottolander GJH. Von Willebrand factor and early diabetic retinopathy:no evidence for a relationship in patients with type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion. Diabetologia 1992; 35: 555-559
27 Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans:insights gained from studies using markers of hemostatic system activation. Blood 1987; 70: 343-350
28 Kanwar YS, Rosenzweig LJ, Linker A, Jakubowski ML. Decreased de novo synthesis of glomerular proteoglycans in diabetes:biochemical and autoradiographic evidence. Proc Natl Acad Sci USA 1983; 80: 2272-2275
29 Villanueva GB, Allen N. Demonstration of altered antithrombin III activity due to nonenzymatic glycosylation at glucose concentration expected to be encountered in severely diabetic patients. Diabetes 1988; 37: 1103-1107
30 Esmon CT, Owen WG. Identification of an endothelial cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-2252
31 Esposito C, Gerlach H, Brett J, Stern D, Vlassara H. Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med 1989; 170: 1387-1407