Much interest surrounds the receptors α2β1 and glycoprotein VI (GPVI) whose synchronized action mediates the attachment and activation of platelets on collagen, essential for preventing blood loss but also the most thrombogenic component of the vessel wall. Subject to density variations on platelets through natural polymorphisms, the absence of α2β1 or GPVI uniquely leads to a substantial block of hemostasis without causing major bleeding. Specific to the megakaryocyte lineage, GPVI and its signaling pathways are most promising targets for anti-thrombotic therapy. This review looks at the clinical consequences of the loss of collagen receptor function with emphasis on both the inherited and acquired loss of GPVI with brief mention of mouse models when necessary. A detailed survey of rare case reports of patients with inherited disease-causing variants of the GP6 gene is followed by an assessment of the causes and clinical consequences of acquired GPVI deficiency, a more frequent finding most often due to antibody-induced platelet GPVI shedding. Release of soluble GPVI is brought about by platelet metalloproteinases; a process induced by ligand or antibody binding to GPVI or even high shear forces. Also included is an assessment of the clinical importance of GPVI-mediated platelet interactions with fibrin and of the promise shown by the pharmacological inhibition of GPVI in a cardiovascular context. The role for GPVI in platelet function in inflammation and in the evolution and treatment of major illnesses such as rheumatoid arthritis, cancer and sepsis is also discussed.

受体α2β1和糖蛋白VI（GPVI）引起了人们的极大兴趣，它们的同步作用介导了胶原蛋白上血小板的附着和激活，这对于防止失血是必不可少的，而且也是血管壁的最血栓形成成分。血小板因自然多态性而受到密度变化的影响，α2β1或GPVI的缺失会唯一地导致实质性止血，而不会引起大出血。GPVI及其信号通路是巨核细胞谱系特有的，是抗血栓治疗的最有希望的靶标。这篇综述着眼于胶原蛋白受体功能丧失的临床后果，重点是遗传性和获得性GPVI丧失，并在必要时简要提及小鼠模型。GP6基因后面是获得性GPVI缺乏症的原因和临床后果的评估，该现象最常见的原因是抗体诱导的血小板GPVI脱落。可溶性GPVI的释放是由血小板金属蛋白酶引起的。由配体或抗体结合GPVI或什至高剪切力诱导的过程。还包括对GPVI介导的血小板与血纤蛋白相互作用的临床重要性的评估，以及在心血管环境中GPVI的药理学抑制作用所显示的希望。还讨论了GPVI在血小板功能中的作用以及在炎症以及主要疾病（如类风湿性关节炎，癌症和败血症）的演变和治疗中的作用。