Molecular determinants of platelet delta storage pool deficiencies: an update

• Published in: British journal of haematology Vol. 160; no. 1; pp. 5 - 11
• Main Authors: Masliah‐Planchon, Julien, Darnige, Luc, Bellucci, Sylvia
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.01.2013
• Subjects: Animals; Biological and medical sciences; cellular trafficking; Chediak-Higashi Syndrome - blood; Chediak-Higashi Syndrome - genetics; Chediak-Higashi Syndrome - pathology; Chediak–Higachi syndrome; Hematologic and hematopoietic diseases; Hermanski-Pudlak Syndrome - blood; Hermanski-Pudlak Syndrome - genetics; Hermanski-Pudlak Syndrome - pathology; Hermansky–Pudlak syndrome; Humans; Medical sciences; molecular analysis; platelet delta storage pool disease; Platelet diseases and coagulopathies; Platelet Storage Pool Deficiency - blood; Platelet Storage Pool Deficiency - genetics; Platelet Storage Pool Deficiency - pathology; Tumors; cellular trafficking; Immunopathology; Skin disease; Hematology; Platelet storage pool deficiency; Metabolic diseases; Hemopathy; Chediak syndrome; Hermansky-Pudlak syndrome; Immune deficiency; Genetic disease; Chediak―Higachi syndrome; Eye disease; Platelet; Cancerology; Hermansky―Pudlak syndrome; platelet delta storage pool disease; molecular analysis; Leukocyte disease
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.12064

Summary Delta storage pool deficiency (δ‐SPD) is a rare heterogeneous group of platelet disorders characterized by a reduction in the number or content of dense granules. δ‐SPD causes a mild to moderate bleeding diathesis characterized mainly by mucocutaneous bleeding. Currently, no specific treatment is available and the therapeutic approach is based on prevention of excessive bleeding. However, during the last few years, important insights into the pathophysiology of δ‐SPD have been achieved using mouse models and dense granule deficiency‐associated congenital diseases, such as Hermansky–Pudlak syndrome and Chediak–Higashi syndrome. It thus appears that δ‐SPD represents a genetically heterogeneous group of intracellular vesicle biogenesis and/or trafficking disorders. This review summarizes recent data regarding the molecular mechanisms together with clinical features of the different types of δ‐SPD. Although the molecular basis of isolated inherited δ‐SPD remains currently unknown, next‐generation sequencing strategies should enable researchers to identify the causative genes. Identification of those genes should contribute to our understanding of the pathophysiology, represent useful tools for genetic diagnosis, and eventually lead to new specific therapeutic approaches.