RESUMEN
The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.
Asunto(s)
Albinismo Oculocutáneo/sangre , Plaquetas/metabolismo , Factor de von Willebrand/fisiología , Adenosina Trifosfato/metabolismo , Adolescente , Adulto , Albinismo Oculocutáneo/fisiopatología , Tiempo de Sangría , Plaquetas/química , Niño , Preescolar , Factor VIII/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/fisiología , Factor Plaquetario 4/análisis , Deficiencia de Almacenamiento del Pool Plaquetario/sangre , Deficiencia de Almacenamiento del Pool Plaquetario/fisiopatología , Puerto Rico/etnología , beta-Tromboglobulina/análisis , Factor de von Willebrand/análisisRESUMEN
The platelet glycoprotein Ib(alpha) (GPIb(alpha)) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb(alpha) that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation induced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptides were synthesized from the peptide sequence F216-T240. Several of the peptides derived from the sequence W219-V227 of GPIb(alpha) inhibited platelet aggregation, which was primarily dependent on the presence of the amino acid sequence A224-N226 (AEN). These data suggest that a region within the GPIb(alpha) chain modulates the platelet aggregation induced by alpha-thrombin. These GPIb(alpha) peptides did not interfere with platelet aggregation induced by other agonists--for example, collagen, ristocetin, calcium ionophore, or botrocetin--which indicates that these GPIb(alpha) peptide-platelet interaction(s) are specific. Our studies provide another potential mechanism for modulating platelet activation and aggregation via synthetic and natural peptides.