Pro-Coagulant Factors
Platelets:
Insulin normally inhibits platelet aggregation. Diabetes Care. 1998 Jan;21(1):121-6 Platelet vascular mechanism are activated in diabetes mellitus evidenced by increase in beta thromboglobulin, platelet factor 4, thromboxane A4 and B2, ICAM 1 and E- selectin and decreased prostaglandin12. Platelets in diabetics have an increased sensitivity to activation under high shear stress. The increased procoagulant nature of the platelets is demonstrated by an increased tendency to ADP induced aggregation.
Fibrinogen:
Fibrinogen levels are raised in diabetes mellitus. Levels are particularly raised due to chronic hypersecretion in those with prolonged poor metabolic control. Hence improved diabetic control should theoretically decrease fibrinogen levels and improve the coagulant status.
Increased fibrinogen levels increase blood viscosity with increased tissue deposition of bigger fibrin clots with stimulation of atherosclerosis. Glycated fibrinogen deposition is probably greater than fibrinogen itself. due to decreased susceptibility to plasmin. These could have impact on macro and microvascular disease initiation and progression. Metformin may have a positive influence on the fibrin structure and the cross linking of fibrin by factor 12 . This improves the hypofibrinolytic state of diabetes.
PAI-1:
High levels of plasminogen activator inhibitor which inhibits fibrinolysis is a feature of type 2 diabetes mellitus. This is an added risk factor for macrovascular disease. Although both t-PA and PAI-1 activity are increased in diabetics, the latter is clearly overpowering due to the net reduction of the free fibrinolytic activity. It is interesting to note in this juncture that in type 1 diabetics without complications PAI-1 activity is normal but when complications occur, the levels are usually high. Metformin reduces PAI-1 by 20%.
Glycated LDL:
An independent factor increasing PAI-1.
Insulin normally inhibits platelet aggregation. Diabetes Care. 1998 Jan;21(1):121-6 Platelet vascular mechanism are activated in diabetes mellitus evidenced by increase in beta thromboglobulin, platelet factor 4, thromboxane A4 and B2, ICAM 1 and E- selectin and decreased prostaglandin12. Platelets in diabetics have an increased sensitivity to activation under high shear stress. The increased procoagulant nature of the platelets is demonstrated by an increased tendency to ADP induced aggregation.
Fibrinogen:
Fibrinogen levels are raised in diabetes mellitus. Levels are particularly raised due to chronic hypersecretion in those with prolonged poor metabolic control. Hence improved diabetic control should theoretically decrease fibrinogen levels and improve the coagulant status.
Increased fibrinogen levels increase blood viscosity with increased tissue deposition of bigger fibrin clots with stimulation of atherosclerosis. Glycated fibrinogen deposition is probably greater than fibrinogen itself. due to decreased susceptibility to plasmin. These could have impact on macro and microvascular disease initiation and progression. Metformin may have a positive influence on the fibrin structure and the cross linking of fibrin by factor 12 . This improves the hypofibrinolytic state of diabetes.
PAI-1:
High levels of plasminogen activator inhibitor which inhibits fibrinolysis is a feature of type 2 diabetes mellitus. This is an added risk factor for macrovascular disease. Although both t-PA and PAI-1 activity are increased in diabetics, the latter is clearly overpowering due to the net reduction of the free fibrinolytic activity. It is interesting to note in this juncture that in type 1 diabetics without complications PAI-1 activity is normal but when complications occur, the levels are usually high. Metformin reduces PAI-1 by 20%.
Glycated LDL:
An independent factor increasing PAI-1.