RESUMEN
BACKGROUND: Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. CASE PRESENTATION: We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no adverse events have been reported. CONCLUSIONS: Oral miglustat therapy proved to be a valid alternative treatment to intravenous enzyme replacement therapy for long-term maintenance in this patient with Gaucher disease type 1, who showed persistent allergic intolerance to imiglucerase infusions. This report exemplifies the type of patient with Gaucher disease type 1 who can benefit from switching from enzyme replacement therapy to substrate reduction therapy.
Asunto(s)
1-Desoxinojirimicina/análogos & derivados , Inhibidores Enzimáticos/administración & dosificación , Terapia de Reemplazo Enzimático/efectos adversos , Enfermedad de Gaucher/tratamiento farmacológico , Bazo/patología , 1-Desoxinojirimicina/administración & dosificación , Adulto , Esquema de Medicación , Erupciones por Medicamentos , Enfermedad de Gaucher/patología , Humanos , Masculino , Calidad de Vida , Bazo/efectos de los fármacos , Resultado del TratamientoAsunto(s)
Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/farmacología , Trombocitemia Esencial/tratamiento farmacológico , Adulto , Anciano , Antitrombina III/análisis , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Quimioterapia Combinada , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Hidroxiurea/efectos adversos , Hidroxiurea/uso terapéutico , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/análisis , Péptido Hidrolasas/análisis , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacología , Recuento de Plaquetas , Factor Plaquetario 4/análisis , Protrombina/análisis , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Trombocitemia Esencial/sangre , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
We prospectively evaluated the effect of anagrelide (ANA) on platelets, PF4, F1+2, PAP, PAI-1, and TFPI and erythromelalgia in patients with essential thrombocythemia (ET) receiving anti-aggregants both pre- and post-ANA. At first, we observed a successful reduction of platelets, which was associated with normalization of platelet coagulant and endothelial function and disappearance of erythromelalgia. Secondly, we found a correlation between PF4 and TFPI and between TFPI and thrombosis, suggesting that erythromelalgia may be caused by platelet-mediated endothelial activation. These data may indicate that ANA may be efficacy in the treatment of symptomatic patients with ET.
Asunto(s)
Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Adulto , Anciano , Coagulación Sanguínea/efectos de los fármacos , Femenino , Humanos , Lipoproteínas/genética , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Factor Plaquetario 4/genética , Trombocitemia Esencial/sangre , Trombosis/sangreRESUMEN
Vascular endothelial growth factor (VEGF) induces platelet activation in a thrombin-dependent manner. We tested the serum VEGF levels in patients with polycythemia vera (PV) and found a significant correlation between increased VEGF and thrombosis. These findings suggest that high VEGF levels might contribute to the occurrence of thrombosis in this hematologic malignancy.