Elevation of factor XIa-alpha 1-antitrypsin complex levels in NIDDM patients with diabetic nephropathy

Excess activated FXIa in plasma indicates hypercoagulability in the early contact phase. We have already developed methods for detecting the hypercoagulable state in clinical samples by our ELISA for complexed FXIa and alpha 1AT, which has been confirmed to be the predominant inhibitor of FXIa. In diabetes, whether the activation of FXI is associated with the development of vascular complications remains unknown, although various hemostatic abnormalities have been described. We tested the complexed FXIa-alpha 1AT level in 45 NIDDM patients, who were divided into three groups according to the development of diabetic nephropathy, as assessed by UAE. Normoalbuminuria was defined as UAE < 15 micrograms/min, microalbuminuria as UAE in the range of 15-200 micrograms/min, and albuminuria as UAE > 200 micrograms/min. In the patients as a whole, FXIa-alpha 1AT and TAT levels were significantly increased compared with these levels in age-matched control subjects (17.3 +/- 5.7 vs. 12.4 +/- 2.4 ng/ml and 2.67 +/- 1.23 vs. 1.93 +/- 0.45 ng/ml, respectively). No significant difference was observed between FXIa-alpha 1AT levels in the control subjects and in the normoalbuminuric group (13.0 +/- 2.1 ng/ml; n = 19). However, in the microalbuminuric (17.9 +/- 3.9 ng/ml; n = 16) and albuminuric (24.1 +/- 5.4 ng/ml; n = 10) groups, FXIa-alpha 1AT levels were significantly increased compared with those in the control and normoalbuminuric group. The TAT level was not correlated with FXIa-alpha 1AT, and no significant differences in its levels were found among these diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)