Significance of Plasma Thrombin-Antithrombin III and Pasmin- 2-Plasmin Inhibitor Complexes in Diabetic Patients

Kim, Kyung Wook; Kim, Un Suk; Chung, Sang Su; Yoon, Soo Jee; Park, Wook Il; Lee, Jun Hee; Nam, Su Youn; Ahn, Chul Woo; Moon, Byung Soo; Kim, Kyung Rae; Cha, Bong Soo; Soung, Young Duk; Lim, Sung Kil; Lee, Hyun Chul; Huh, Gap Bum

Abstract

BACKGROUND: Abnormality of coagulation and fibrinolytic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication.
METHODS
In our study, we measured plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication.
RESULTS
1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA1c, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8 1.2 ng/mL, 240.4+/-69.7 ng/mL in controls and 9.5+/-22.6 ng/mL, 472.2+/-258.7 ng/mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1+/-2.4 ng/mL, 362.2+/-272.0 ng/mL, 322.7+/-102.4 mg/dL in group without vascular complication and 5.3+/-4.1 ng/mL, 529.5+/-258.7 ng/mL, 374.9+/-106.2 mg/dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 6.0+/-4.9 ng/mL, 507.4+/-321.6 ng/mL, 427.1+/-194.7 mg/dL in macrovascular complication, and 10.4+/-6.7 ng/mL, 484.8+/-269.7 ng/mL, 388.4+/-132.4 mg/dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA1c (r=0.67).
CONCLUSION
In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro- macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA1c. TAT was correlated with HbA1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients.