A novel type of macrothrombocytopenia associated with a defect in ?2,3-sialylation.

Jones C, Denecke J, Sträter R, Stölting T, Schunicht Y, Zeuschner D, Klumperman J, Lefeber DJ, Spelten O, Zarbock A, Kelm S, Strenge K, Haslam SM, Lühn K, Stahl D, Gentile L, Schreiter T, Hilgard P, Beck-Sickinger AG, Marquardt T, Wild MK

Zusammenfassung

We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to ?2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of ?2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.