A New Genetic Isolate of Gray Platelet Syndrome (GPS): Clinical, Cellular, and Hematologic Characteristics

• Published in: Molecular genetics and metabolism 2001-11, Vol.74 (3), p.303-313
• Main Authors: Falik-Zaccai, Tzipora C, Anikster, Yair, Rivera, Candido E, Horne, McDonald K, Schliamser, Liliana, Phornphutkul, Chanika, Attias, Dina, Hyman, Tehila, White, James G, Gahl, William A
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Antigens, CD - analysis; Blood Platelets - pathology; Blood Platelets - ultrastructure; Child; Family Health; Female; fibrinogen receptor; Flow Cytometry; genetic isolate; gray platelet syndrome; Humans; Immunohistochemistry; Integrin beta3; Male; Megakaryocytes - chemistry; Microscopy, Electron; P-selectin; P-Selectin - analysis; Pedigree; Peptide Fragments - pharmacology; Platelet Activation - drug effects; Platelet Count; Platelet Glycoprotein GPIb-IX Complex - metabolism; Platelet Membrane Glycoproteins - analysis; Platelet Storage Pool Deficiency - blood; Platelet Storage Pool Deficiency - genetics; Platelet Storage Pool Deficiency - pathology
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1006/mgme.2001.3247

Gray platelet syndrome (GPS) is a disorder characterized by thrombocytopenia and large platelets that lack α granules and their contents. We describe two siblings with GPS who are members of a Moslem Bedouin genetic isolate. The children, an 8-year-old girl and a 5-year-old boy, had characteristic pale blue platelets lacking α granules on electron microscopy. Platelet aggregation studies were normal. The girl underwent a bone marrow aspiration and biopsy which showed mild myelofibrosis and extensive emperipolesis, i.e., the passage of other hematopoietic cells through megakaryocytes. Both children lacked high-molecular-weight multimers of von Willebrand factor (vWF) and had reduced activity and antigens of vWf. Platelet activation was approximately normal when ADP was employed as agonist, but significantly impaired using the thrombin receptor-activating peptide (TRAP). These findings are explained in light of the mechanism of action of each agonist. In addition, we propose that the emperipolesis was caused by increased P-selectin in megakaryocytes, and resulted in release of fibroblastic growth factors, explaining the myelofibrosis. The detailed description of these cases provides a basis for future differentiation of the various types of GPS, and for our current attempts to isolate the gene causing GPS in this genetic isolate.