Inherited thrombocytopenias: history, advances and perspectives.

Inherited thrombocytopenias: history, advances and perspectives. Haematologica. 2020 Jun 11;: Authors: Nurden AT, Nurden P Abstract Within the last 100 years the role of platelets in hemostatic events and their production by megakaryocytes (MKs) has been gradually defined. Progressively, thrombocytopenia was recognized as a cause of bleeding, first through an acquired immune disorder; then from 1948 when the Bernard-Soulier syndrome was first described, inherited thrombocytopenia has become a fascinating source of Mendelian disease. Often the platelet count is severely decreased and platelet size variable; associated platelet function defects often aggravate bleeding. Macrothrombocytopenia (MTP) with enlarged platelets in variable proportions is common. The circulating count will depend on platelet production, consumption and lifespan. The bulk of MTPs arise from defects in megakaryopoiesis with causal variants in transcription factor genes giving rise to altered stem cell differentiation and changes in early MK development and maturation. Genes encoding surface receptors, cytoskeletal and signaling proteins also feature prominently and Sanger sequencing associated with careful phenotyping allowed their early classification. It quickly become apparent that many inherited thrombocytopenias are syndromic while others are linked to an increased risk of hematological malignancies. The application the last 10 years of Next Generation Sequ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research