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Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients
E Porreca1, M D Guglielmi, A Uncini
1Department of Internal Medicine, University of Chieti, Medical School, Italy.
Insights
Patients with Duchenne and Becker muscular dystrophy exhibit a hypercoagulable state, indicated by elevated markers of blood clotting and tumor necrosis factor-alpha (TNF-alpha). These findings suggest a link between clotting activation, cardiac dysfunction, and TNF-alpha in muscular dystrophy.
Area of Science:
- Cardiology
- Hematology
- Genetics
Background:
- Cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD) can lead to left ventricular thrombosis and systemic emboli.
- Tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine, is elevated in patients with cardiac dysfunction.
Purpose of the Study:
- To investigate plasma levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TAT), and TNF-alpha in patients with DMD and BMD.
- To explore the relationship between hemostatic activation, cardiac function, and TNF-alpha in these patient groups.
Main Methods:
- Measured plasma levels of F1+2, TAT, and TNF-alpha in 20 DMD patients, 12 BMD patients, and 30 age-matched controls.
- Analyzed correlations between F1+2, TAT, left ventricular ejection fraction, and TNF-alpha levels.
Main Results:
- Significantly elevated levels of F1+2, TAT, and TNF-alpha were observed in DMD and BMD patients compared to controls.
- Negative correlations were found between F1+2/TAT and left ventricular ejection fraction.
- Positive correlations were found between F1+2/TAT and serum TNF-alpha levels.
Conclusions:
- X-linked dystrophic patients present with a hypercoagulable state.
- A potential relationship exists between hemostatic activation, left ventricular dysfunction, and TNF-alpha system upregulation in muscular dystrophy.
Abstract:
Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A significantly negative correlation was also found between F1+2 and TAT complexes and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.