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Essential thrombocythemia (ET) is a chronic myeloproliferative disease, rarely observed in pediatric age, characterized by a persistently increased platelet count. Abnormalities of platelet function observed in ET patients may be, at least in part, responsible for the thrombohemorrhagic complications. The authors report about a pediatric patient affected by ET, showing an abnormal platelet response following stimulation by anti-platelet monoclonal antibody. Such finding may be attributable to a structural abnormality of the platelet fibrinogen receptor or to post-receptor alterations.

Glanzmann's thrombasthenia is an autosomal recessive life-long bleeding disorder, originated from a quantitative or qualitative defect of the major platelet membrane receptor: the GPIIb/IIIa complex. The GPIIb/IIIa complex is a calcium-dependent heterodimer, belonging to the integrin superfamily. The complex of activated platelets can bind fibrinogen, von Willebrand factor, fibronectin and vitronectin, which are proteins playing an important role in platelet adhesion and aggregation. Thrombasthenic platelets are deficient in GPIIb, GPIIIa and GPIIb/IIIa complex; however, platelets from few thrombasthenic patients content near-normal amounts of functionally abnormal complex. The GPIIb/IIIa quantitative or functional defect leads to defective platelet hemostatic plug formation. Hemorrhagic symptoms consist of purpura, gingival hemorrhage, menorrhagia and epistaxis. Some cases of Glanzmann's thrombasthenia have been characterized at the molecular genetic level. Molecular abnormalities include: GPIIb or GPIIIa partial gene deletion, GPIIIa gene insertion, a point mutation resulting in an amino acid substitution within the GPIIIa molecule. In spite of the contemporary reduction of both GPIIb and GPIIIa in most cases of Glanzmann's thrombasthenia, it appears that a molecular abnormality affecting only one of the glycoprotein genes may result in a thrombasthenic phenotype.

The glycoprotein (GP) IIb/IIIa complex is the most abundant platelet membrane receptor (approximately 80,000 copies/platelet). The GP IIb/IIIa complex is an adhesion receptor belonging to the integrin superfamily; it can bind five adhesive proteins containing the arginine-glycine-aspartic acid (RGD) sequence in their structure: fibrinogen (Fg), von Willebrand factor (vWf), thrombospondin (Tsp), fibronectin (Fn) and vitronectin (Vn). Fg mediates platelet aggregation; vWf, Tsp and Fn are large molecules that support platelet adhesion to vessel wall; Vn is a molecular connection among hemostasis and others physiological processes. The complex is presents at any time on the platelet surface, but macromolecular ligands cannot access to their receptor because of steric hindrances intrinsic to the complex itself or its microenvironment. Adhesive proteins can bind to the complex only after platelets become activated; following platelet stimulation and ligand binding a conformational change takes place, accompanied by expression of new epitopes termed LIBS (ligand-induced binding sites). The complex-bound fibrinogen undergoes to a progressive rearrangement which increases the adhesive function of the molecule. The RGD sequence present in adhesive proteins, in addition to its receptor role, may serve as a trigger sequence that induces a high affinity ligand-binding state in the GP IIb/IIIa complex. The different domains of adhesive proteins can bind to platelet surface receptors, other than GP IIb/IIIa, so realizing multiple ligand-receptor interactions.