Faculty Bibliography

The mechanisms for the variability in antiplatelet effects of clopidogrel are not elucidated entirely. Immature (reticulated) platelets may modulate the antiplatelet effects of clopidogrel but must be measured using flow cytometry. Whether new automated detection techniques yield similar results is not known. The objectives of the study to evaluate the role of immature platelets assessed by an automated method in response to the antiplatelet effects of clopidogrel. Twenty-nine healthy volunteers had platelet studies performed before and 1 week after 75 mg daily dosing of clopidogrel. Immature platelet fraction (IPF) was determined using an automated particle counter. Subjects were stratified into tertiles based on the IPF. Platelet studies included light transmission aggregometry (LTA), and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) determined by platelet reactivity index (PRI). Baseline platelet aggregation responses to 2, 5 and 20 muM ADP, were similar in all three tertiles, however they were greater in the upper than in the lower tertile of immature platelets after clopidogrel in response to 5 muM ADP (54% vs. 23%, P = 0.02), with concordant trends for the other two concentrations. PRI was also greater in the upper tertile after clopidogrel (71.2% vs. 57.8%, P = 0.04). The frequency of clopidogrel hyporesponsiveness (aggregation >50% in response to 5 muM of ADP) was also higher in the upper tertile when compared to lower tertile, (60%) versus (10%) respectively (P = 0.02). [corrected]. Immature platelets measured using an automated method, are associated with impaired response to antiplatelet effects of clopidogrel.

Autoimmunity plays a major role in the pathogenesis of many neuromuscular disorders such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, polymyositis, dermatomyositis, myasthenia gravis, Lambert Eaton syndrome, and stiff person syndrome. Although most of these disorders respond favorably to the commonly used immunomodulatory agents such as steroids, intravenous gamma globulin, plasmapheresis, and chemotherapy, some are initially refractory, whereas others gradually lose responsiveness. Therefore, alternative, selective, and novel immunosuppressive agents are used to treat these cases. Among these agents, rituximab has shown promise in some of the neuromuscular disorders with minimal side effects. Rituximab is a genetically engineered antibody that depletes CD20+ B-cells and is Food and Drug Administration- approved for treatment of non-Hodgkin lymphoma, CD20+ CLL, and rheumatoid arthritis. It carries a favorable side effects profile. However, evidence of efficacy is limited to case series and large prospective randomized controlled trials are lacking. In this article, we review and discuss the available literature on rituximab in treatment of various autoimmune neuromuscular diseases.