G.P. Somov Institute of Epidemiology and Microbiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 690087 Vladivostok, Russia.
School of Biomedicine, Far Eastern Federal University (FEFU), 690091 Vladivostok, Russia.
Molecules. 2021 Apr 29;26(9):2618. doi: 10.3390/molecules26092618.
Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.
止血障碍在 COVID-19 的发病机制、临床表现和结果中起着重要作用。首先，由于 COVID-19 的复杂和严重病程，止血系统受到影响。相当数量的 COVID-19 患者出现高凝、血小板减少和纤维蛋白溶解亢进的迹象。重症 COVID-19 患者有静脉和动脉系统血栓并发症的倾向，这是该病的主要死亡原因。尽管在治疗 SARS-CoV-2 方面取得了成功，但寻找新的有效抗凝剂、溶栓剂和纤维蛋白溶解剂及其最佳剂量策略仍然具有相关性。海藻硫酸多糖 (PSs) 的广泛治疗潜力，包括抗凝、溶栓和纤维蛋白溶解活性，为其在实验和临床试验中的研究开辟了新的可能性。与合成药物相比，这些天然化合物由于其天然来源、安全性和低成本，可能成为止血障碍恢复的重要补充药物。在这篇综述中，作者分析了 COVID-19 病理进展中观察到的止血障碍所涉及的可能的病理生理机制，还将研究人员的注意力集中在海藻 PSs 上，将其作为纠正 COVID-19 患者这些障碍的潜在药物。根据其结构特征（PSs 主链上硫酸基团的含量和位置、分子量、单糖组成和糖苷键类型、PS 链分支程度等），介绍了海藻 PSs 的抗凝、抗血栓和纤维蛋白溶解活性的现代文献数据。考虑了 PSs 对止血系统的作用机制以及 PSs 的口服生物利用度问题，这对于将 PSs 作为口服抗凝剂和抗血栓药物临床应用非常重要。PSs 的抗凝、溶栓和纤维蛋白溶解特性的结合，以及低毒性和相对低廉的生产成本，为将 PSs 作为新型抗凝和抗血栓化合物的替代来源的临床应用开辟了前景。然而，需要进一步的研究和临床试验来证实其疗效。
