Increased tissue factor pathway inhibitor (TFPI) and coagulation in patients with insulin-dependent diabetes mellitus.
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.
Leurs
P B
PB
Department of Internal Medicine, University Hospital, Maastricht, The Netherlands.
van Oerle
R
R
Wolffenbuttel
B H
BH
Hamulyak
K
K
D000328:Adult; D000704:Analysis of Variance; D000925:Anticoagulants / Q000097:blood*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism
D000925:Anticoagulants; D008074:Lipoproteins; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III; D011516:Prothrombin; D013917:Thrombin