Kaya Zühre
Department of Pediatrics, Unit of Pediatric Hematology, Faculty of Medicine, Gazi University, Ankara, Türkiye.
Semin Thromb Hemost. 2025 Mar;51(2):209-218. doi: 10.1055/s-0044-1789184. Epub 2024 Aug 27.
Bernard-Soulier syndrome (BSS) is an inherited platelet function disorder caused by mutations in the genes that encode the glycoprotein (GP) Ibα and GPIbβ subunits, as well as the GPIX subunit in the GPIbIX complex, which is located on the platelet surface and has roles in platelet adhesion and activation. Patients with autosomal recessively inherited biallelic BSS have a homozygous or compound heterozygous expression in the GPIbα, GPIbβ, and GPIX subunits of the GPIbIX complex. Patients with autosomal dominantly inherited monoallelic BSS have a heterozygous expression in only the GPIbα and GPIbβ subunits of the GPIbIX complex. To date, no BSS mutations in the gene have been reported. Patients with biallelic form are usually diagnosed at a young age, typically with mucocutaneous bleeding, whereas monoallelic forms are generally identified later in life and are frequently misdiagnosed with immune thrombocytopenic purpura (ITP). In biallelic BSS, giant platelets in the peripheral blood smear, absence of ristocetin-induced platelet aggregation (RIPA) using light transmission aggregometry (LTA), and complete loss of GPIbIX complex in flow cytometry are observed, whereas in monoallelic forms, genetic diagnosis is recommended due to the presence of large platelets in the peripheral blood smear, decreased or normal RIPA response in LTA, and partial loss or normal GPIbIX complex in flow cytometry. Platelet transfusion is the main therapy but recombinant factor VIIa is advised in alloimmunized patients, and allogeneic stem cell transplantation is suggested in refractory cases. Antifibrinolytics and oral contraceptives are utilized as supplementary treatments. Finally, differentiation from ITP is critical due to differences in management. Thus, BSS should be kept in mind in the presence of individuals with chronic persistent thrombocytopenia, positive family history, unresponsive ITP treatment, macrothrombocytopenia, and absence of RIPA response.
伯纳德-索利尔综合征（BSS）是一种遗传性血小板功能障碍，由编码糖蛋白（GP）Ibα和GPIbβ亚基以及GPIbIX复合物中GPIX亚基的基因突变引起，该复合物位于血小板表面，在血小板黏附和激活中起作用。常染色体隐性遗传双等位基因BSS患者在GPIbIX复合物的GPIbα、GPIbβ和GPIX亚基中有纯合或复合杂合表达。常染色体显性遗传单等位基因BSS患者仅在GPIbIX复合物的GPIbα和GPIbβ亚基中有杂合表达。迄今为止，尚未报道该基因中的BSS突变。双等位基因形式的患者通常在年轻时被诊断出来，典型症状为皮肤黏膜出血，而单等位基因形式通常在生命后期被发现，且常被误诊为免疫性血小板减少性紫癜（ITP）。在双等位基因BSS中，在外周血涂片上可观察到巨大血小板，使用光透射聚集法（LTA）检测时无瑞斯托霉素诱导的血小板聚集（RIPA），且流式细胞术中GPIbIX复合物完全缺失；而在单等位基因形式中，由于外周血涂片上有大血小板、LTA中RIPA反应降低或正常、流式细胞术中GPIbIX复合物部分缺失或正常，建议进行基因诊断。血小板输注是主要治疗方法，但对于同种免疫患者建议使用重组因子VIIa，难治性病例建议进行异基因干细胞移植。抗纤溶药物和口服避孕药用作辅助治疗。最后，由于治疗方法不同，与ITP进行鉴别诊断至关重要。因此，对于存在慢性持续性血小板减少、家族史阳性、ITP治疗无反应、大血小板减少症以及无RIPA反应的个体，应考虑BSS。
