TAFI and Diabetics.

Background: A novel risk factor for thrombotic disorders is thrombin activatable fibrinolysis inhibitor (TAFI) which is also known as plasma procarboxypeptidase B. TAFI is a potent inhibitor of tissue plasminogen activator - induced fibrinolysis, impairing the process of clot lysis and causing a tendency to thrombosis development. The increased circulating plasma levels of TAFI were reported in type 2 diabetes mellitus (DM), obesity, insulin resistance and in hypercholesterolemic subjects. TAFI plasma level was significantly higher in diabetic patients with microalbuminuria than those in diabetic patients with normoalbuminuria and normal subjects. These authors suggest that increased plasma level of TAFI may be involved not only in hypofibrinolysis but also in the mechanism of vascular endothelial damage in patients with type 2 DM.

Aim of study: We evaluated the activity of activated TAFI (TAFIa) and its relation to another hemostatic and metabolic parameters in patients with diabetic nephropathy (DN).

Patients and methods: Eighteen patients (pts) with diabetic nephropathy (DN) − 14 pts type 2 DM / 4 pts type 1 DM, age 54,1±13,3 years (12 men, 6 women), fourteen pts with non-diabetic nephropathy (NDN), age 49,7±15,6 years (7 men, 7 women) and twenty healthy subjects were enrolled in the study. TAFIa (Actichrome Activity TAFI kit, American Diagnostica), soluble thrombomodulin TM (sTM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hcy), D-dimers plasma levels and metabolic parameters including glycosylated hemoglobin (HbA1c) were measured.

Results: TAFIa plasma levels in DN pts were significantly decreased compared to NDN pts (7,22 ± 3,54 vs. 12,67 ± 6,99 ug/ml, p<0,01, respectively). After analysis the significant TAFIa decrease was only in those DN pts with hypercreatinemia and proteinuria. The sTM levels showed significant increase in DN pts with hypercreatinemia (p<0,0001). There was a significant positive correlation between TAFIa and HbA1c (r=0,50931, p<0,05).

Conclusion: TAFIa plasma levels didn′t differ significantly in patients with diabetic nephropathy compared to those in control healthy group. Decreased TAFIa plasma levels in our DN pts with proteinuria and hypercreatinemia compared to NDN group may be due to the secondary (compensatory) increased fibrinolysis as a consequence of hypercoagulability in pts with DM. TAFIa was in a close relation to the metabolic compensation of DM (HbA1c) that can be of clinical importance for DN pts.