Bernard-Soulier Syndrome: An Update

Abstract

Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIbα disulfide linked to GPIbβ, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIbα, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin αMβ2), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIbα cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3ζ and the p85 subunit of phosphoinositide 3-kinase. GPIbα is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment.

The utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool and other bleeding questionnaires in assessing the bleeding phenotype in two platelet function defects

“…There was also no significant difference in bleeding score between Glanzmann's thrombasthenia and BSS patients using either of the bleeding questionnaires. As previously reported [18,27], patients with Glanzmann's thrombasthenia had a normal platelet count (mean ¼ 244 Â 10 9 /l); however, patients with BSS showed thrombocytopenia (mean ¼ 84 Â 10 9 /l).…”

“…BS, bleeding score, BSS, Bernard-Soulier syndrome; eBQ, electronic bleeding questionnaire; GT, Glanzmann's thrombasthenia; ISTH-BAT, International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool; MPV, mean platelet volume. however, patients with BSS are known to have macrothrombocytopenia [18].…”

“…Patients show early bleeding symptoms including epistaxis, gingival and gastrointestinal bleeding and ecchymosis, which may range from mild to life-threatening bleeding. An update of the disease has been recently reported [18]. While the diagnosis of these disorders has been established over decades, the assessment of bleeding severity has not been performed.…”

Current State and Novel Approaches of Antiplatelet Therapy

“…On one hand, the rare congenital or acquired defects or deficiency of GPIb-IX-V (Bernard-Soulier syndrome) or GPVI results in variable bleeding risk, from relatively mild to more severe, which could argue against directly targeting these receptors. [64][65][66][67] On the other hand, these cases often involve thrombocytopenia or concurrent hemostatic disorders that complicate attributing bleeding to receptor dysfunction alone. Experimental studies suggest that GPIbα has a far greater contribution to stable arterial thrombosis than vWF, 67 whereas the GPVI-binding sites of collagen are not normally exposed to circulating platelets.…”

Thrombocytopathy

“…Синд ром Бернара-Сулье проявляется значительной кро воточивостью микроциркуляторного и смешанно-го типа, которая проявляется сразу после рождения. Наследование -аутосомно-рецессивное [32].…”