Impaired secretion of platelet granules in patients with Duchenne muscular dystrophy - results of a prospective diagnostic study.

A tendency to bleed during scoliosis surgery has been reported repeatedly in Duchenne muscular dystrophy (DMD) and diagnostic studies show a prolonged bleeding time. The pathophysiological background is still not fully understood. The short dystrophin isoform dp71 is expressed in platelets and mediates contractile properties. We performed a bicentric, non-blinded, prospective diagnostic study in 53 patients with confirmed DMD. Extensive laboratory analyses included platelet aggregometry and platelet flow cytometry, as well as routine coagulation analyses. Results of laboratory diagnostics were correlated with clinical data. Patients were subgrouped and analyzed according to ambulatory status and cardiac involvement. Platelet aggregation was reduced after stimulation with ADP (adenosine triphosphate) [60%; reference range 66-84%]. In addition, in the DMD cohort the expression of platelet activation markers CD62 and CD63 (flow cytometry analyses) was significantly lower than in healthy controls, most prominent in non-ambulatory patients with cardiac involvement. There was no clear association with the location of the underlying mutations in the dystrophin gene. No further abnormalities were identified regarding primary or secondary hemostasis. This study shows that platelets of patients with DMD have decreased expression of CD62 and CD63 which are markers for platelet granule release. This may indicate that patients with DMD have an impaired platelet granule secretion which may explain to some extent the increased bleeding, especially in mucocutaneous areas and perioperatively.

Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.