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Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus
F Carmassi1, M Morale, R Puccetti
1Institute of 2nd Medical Clinic, University of Pisa, Italy.
Insights
Diabetic patients show an impaired hemostatic balance with higher Fibrinogen, Factor VII, Thrombin-Antithrombin complexes, and Plasminogen Activator Inhibitor-1 activity. Poor metabolic control exacerbates these coagulation changes, suggesting a hypercoagulable state contributing to atherosclerosis.
Area of Science:
- Biochemistry
- Hematology
- Endocrinology
Background:
- Diabetes mellitus is associated with an increased risk of atherosclerotic complications.
- Hemostatic balance plays a crucial role in cardiovascular health.
- Understanding coagulation and fibrinolysis in diabetes is vital for risk stratification.
Purpose of the Study:
- To investigate coagulation and fibrinolytic parameters in patients with insulin-dependent diabetes mellitus (IDDM).
- To assess the impact of metabolic control on hemostatic function in IDDM.
- To explore the relationship between hemostatic alterations and diabetic complications.
Main Methods:
- Functional evaluation of coagulation and fibrinolytic parameters including Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, and tissue-Plasminogen Activator.
- Measurement of antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes, and B beta 15-42 fibrin peptide.
- Comparison between 40 IDDM patients with varying metabolic control and 30 healthy controls.
Main Results:
- Diabetic patients exhibited significantly higher Fibrinogen, Factor VII, Thrombin-Antithrombin complexes, and Plasminogen Activator Inhibitor-1 activity compared to controls.
- Reduced tissue-Plasminogen Activator activity was observed in diabetic patients despite normal antigen levels.
- Elevated Factor VII and Thrombin-Antithrombin complexes were specifically noted in patients with poor metabolic control.
- Fibrinogen levels correlated positively with fasting blood glucose and were higher in patients with nephropathy or neuropathy.
Conclusions:
- IDDM patients demonstrate an impaired hemostatic balance, leaning towards a hypercoagulable state.
- These hemostatic alterations, particularly those linked to poor glycemic control, are significant factors in the pathogenesis of diabetic atherosclerotic complications.
- Targeting hemostatic dysregulation may offer therapeutic avenues for reducing cardiovascular risk in diabetes.
Abstract:
Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.