Effects of body composition on the procoagulant imbalance in obese patients.

Obesity is associated with increased thrombotic risk and hypercoagulability whose main driver is an excess of coagulation factor VIII relative to protein C. The aims of this study were to evaluate the association between factor VIII, protein C, factor VIII-to-protein C ratio and bioimpedance parameters of body composition in obese patients. We analysed blood from 69 obese patients and 23 non-obese healthy controls. Plasma levels of factor VIII, protein C, and factor VIII-to-protein C ratio were correlated with total fat, visceral fat, and muscle mass. Compared to controls, obese patients had significantly higher factor VIII (110.5% vs 78.05%, p < 0.001), protein C (120.99% versus 110.51%, p = 0.014), and factor VIII-to-protein C ratio (0.93 versus 0.73, p = 0.002). In obese patients, factor VIII correlated with body-mass index, body fat percentage, muscle mass percentage, and fat-to-muscle ratio, whereas protein C had significant relationships with body fat percentage, muscle mass percentage and fat-to-muscle ratio, but not with body-mass index. Factor VIII-to-protein C ratio > 1 was significantly associated with body-mass index (odds ratio 1.08, 95% CI 1.02 to 1.14) and fat-to-muscle ratio (odds ratio 2.47, 95% CI 1.10 to 5.55). Factor VIII-to-protein C ratio strongly correlated with D-dimer levels in the overall population (rho 0.44, p < 0.001) and obese patients (rho 0.41, p < 0.001). In obese patients, bioimpedance measures of body fat and muscle mass percentage were associated with factor VIII and protein C. Factor VIII-to-protein C ratio was strongly associated with fat-to-muscle ratio and only modestly related to BMI.

A missense mutation W797R in the myophosphorylase gene in a Spanish patient with McArdle's disease.

We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous T-to-C transition results in the replacement of a highly conserved tryptophan at amino acid position (aa) 797 with an arginine in the C-terminal domain of the PYGM protein. The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the aa 797 in the normal function of the PYGM protein. Our data further expand the genetic heterogeneity in patients with McArdle's disease.