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Diabetologia. 2006 May;49(5):1071-80. Epub 2006 Mar 16.

Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus.

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Academic Unit of Molecular Vascular Medicine, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Clarendon Way, Leeds LS1 3EX, UK.



The aim of this study was to determine the influence of type 2 diabetes on fibrinolysis by assessing interactions between the regulatory components of fibrinolysis and the fibrin clot, using fibrinogen purified from 150 patients with type 2 diabetes and 50 matched controls.


Clot lysis rates were determined by confocal microscopy. Plasmin generation was measured using a plasmin-specific chromogenic substrate. Surface plasmon resonance was used to determine the binding interactions between fibrin, tissue-type plasminogen activator (t-PA) and Glu-plasminogen; cross-linkage of plasmin inhibitor to fibrin by factor XIII was determined using a microtitre plate assay.


Lysis of diabetic clots was significantly slower than that of controls (1.35 vs 2.92 microm/min, p<0.0001) and plasmin generation was significantly reduced. The equilibrium binding affinity between both t-PA and Glu-plasminogen and fibrin was reduced in diabetic subjects: t-PA, K (D)=0.91+/-0.3 micromol/l (control subjects), 1.21+/-0.5 micromol/l (diabetic subjects), p=0.001; Glu-plasminogen, K (D)=97+/-19 nmol/l (control subjects), 156+/-66 nmol/l (diabetic subjects), p=0.001. Cross-linkage of plasmin inhibitor to fibrin by factor XIII was enhanced in diabetic subjects, with the extent of in vitro cross-linkage correlating with in vivo glycaemic control (HbA(1c)) (r=0.59, p=0.001).


These results indicate that impairment of the fibrinolytic process in diabetic patients is mediated via a number of different mechanisms; these may be a consequence of post-translational modifications to fibrinogen molecules, resulting from their exposure to the abnormal metabolic milieu associated with diabetes.

[Indexed for MEDLINE]

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