Research progress on the relationship between platelets and complements

doi:10.3969/j.issn.1673-8640.2026.07.016

Abstract

Abstract:

There is a complex relationship between immune system activation and thrombosis，especially in the complement system of the innate immune response. The complement system is a part of the immune system，not only providing natural defense and mediating inflammatory responses，but also being associated with the activation of platelets and thrombosis. Some components of the complement system，such as complement 3（C3），complement 5（C5） and membrane attack complex，can participate in regulating platelet activation and thrombosis，and activated platelets will further activate the complement system. However，the mechanism of this interaction still needs further exploration. This review focuses on the research on the relationship between platelets and complements in recent years，as well as the role of this relationship in diseases characterized by thrombosis and complement activation.

Key words: Platelet, Complement, Thrombosis, Immune response, Disease

CLC Number:

R446.11

YU Mengyao, WANG Chunyan, QIAO Rui, HUANG Shengkai, GONG Hengwen, CUI Chanjuan. Research progress on the relationship between platelets and complements[J]. Laboratory Medicine, 2026, 41(7): 708-713.

Figures/Tables 2

References 46

[1]	Jurk K, Kehrer B E. Platelets:physiology and biochemistry[J]. Semin Thromb Hemost, 2024, 50(5):794-803. DOI URL
[2]	Rawish E, Nording H, Münte T, et al. Platelets as mediators of neuroinflammation and thrombosis[J]. Front Immunol, 2020, 11:548631. DOI URL
[3]	Huilcaman R, Venturini W, Fuenzalida L, et al. Platelets,a key cell in inflammation and atherosclerosis progression[J]. Cells, 2022, 11(6):1014. DOI URL
[4]	Mcmurray J C, Schornack B J, Weskamp A L, et al. Immunodeficiency:complement disorders[J]. Allergy Asthma Proc, 2024, 45(5):305-309. DOI URL
[5]	Coss S L, Zhou D, Chua G T, et al. The complement system and human autoimmune diseases[J]. J Autoimmun, 2023, 137:102979. DOI URL
[6]	Ghebrehiwet B, Geisbrecht B V, Xu X, et al. The C1q receptors:focus on gC1qR/p33(C1qBP,p32,HABP-1)1[J]. Semin Immunol, 2019, 45:101338. DOI URL
[7]	Linge C P, Jern A, Tydén H, et al. Enrichment of complement,immunoglobulins,and autoantibody targets in the proteome of platelets from patients with systemic lupus erythematosus[J]. Thromb Haemost, 2022, 122(9):1486-1501. DOI URL
[8]	Delila L, Wu Y W, Nebie O, et al. Extensive characterization of the composition and functional activities of five preparations of human platelet lysates for dedicated clinical uses[J]. Platelets, 2021, 32(2):259-272. DOI PMID
[9]	Hamad O A, Ekdahl K N, Nilsson P H, et al. Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets[J]. J Thromb Haemost, 2008, 6(8):1413-1421. DOI PMID
[10]	Dobó J, Kocsis A, Farkas B, et al. The lectin pathway of the complement system-activation,regulation,disease connections and interplay with other(proteolytic) systems[J]. Int J Mol Sci, 2024, 25(3):1566. DOI URL
[11]	Golomingi M, Kohler J, Jenny L, et al. Complement lectin pathway components MBL and MASP-1 promote haemostasis upon vessel injury in a microvascular bleeding model[J]. Front Immunol, 2022, 13:948190. DOI URL
[12]	Thurman J M, Fremeaux-bacchi V. Alternative pathway diagnostics[J]. Immunol Rev, 2023, 313(1):225-238. DOI URL
[13]	De Bont C M, Boelens W C, Pruijn G J M. NETosis,complement,and coagulation:a triangular relationship[J]. Cell Mol Immunol, 2019, 16(1):19-27. DOI
[14]	Del Conde I, Crúz M A, Zhang H, et al. Platelet activation leads to activation and propagation of the complement system[J]. J Exp Med, 2005, 201(6):871-879. DOI PMID
[15]	Saggu G, Cortes C, Emch H N, et al. Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H₂O)[J]. J Immunol, 2013, 190(12):6457-6467. DOI PMID
[16]	Hamad O A, Mitroulis I, Fromell K, et al. Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18[J]. Thromb Haemost, 2015, 114(6):1207-1217. DOI URL
[17]	Mishra N, Mohata M, Narang R, et al. Altered expression of complement regulatory proteins CD35,CD46,CD55,and CD59 on leukocyte subsets in individuals suffering from coronary artery disease[J]. Front Immunol, 2019, 10:2072. DOI URL
[18]	Sauter R J, Sauter M, Reis E S, et al. Functional relevance of the anaphylatoxin receptor C3aR for platelet function and arterial thrombus formation marks an intersection point between innate immunity and thrombosis[J]. Circulation, 2018, 138(16):1720-1735. DOI PMID
[19]	Mickael C, Jordan M, Posey J N, et al. Activation of platelets and the complement system in mice with Schistosoma-induced pulmonary hypertension[J]. Am J Physiol Lung Cell Mol Physiol, 2024, 327(5):L661-L668.
[20]	任贵生, 陈文萃. 补体与急性肾损伤[J]. 肾脏病与透析肾移植杂志, 2018, 27(5):468-472.
[21]	Mannes M, Pechtl V, Hafner S, et al. Complement and platelets:prothrombotic cell activation requires membrane attack complex-induced release of danger signals[J]. Blood Adv, 2023, 7(20):6367-6380. DOI PMID
[22]	Noris M, Galbusera M. The complement alternative pathway and hemostasis[J]. Immunol Rev, 2023, 313(1):139-161. DOI URL
[23]	Eriksson O, Mohlin C, Nilsson B, et al. The human platelet as an innate immune cell:interactions between activated platelets and the complement system[J]. Front Immunol, 2019, 10:1590. DOI PMID
[24]	Kohli S, Shahzad K, Jouppila A, et al. Thrombosis and inflammation-a dynamic interplay and the role of glycosaminoglycans and activated protein C[J]. Front Cardiovasc Med, 2022, 9:866751. DOI URL
[25]	Karasu E, Demmelmaier J, Kellermann S, et al. Complement C5a induces pro-inflammatory microvesicle shedding in severely injured patients[J]. Front Immunol, 2020, 11:1789. DOI PMID
[26]	Brown N, Sullo N, Tyson N, et al. Acute kidney injury after cardiac surgery is associated with platelet activation[J]. J Thromb Haemost, 2025, 23(9):2776-2789. DOI PMID
[27]	Taus F, Salvagno G, Canè S, et al. Platelets promote thromboinflammation in SARS-CoV-2 pneumonia[J]. Arterioscler Thromb Vasc Biol, 2020, 40(12):2975-2989. DOI PMID
[28]	Gauer J S, Ajjan R A, Ariëns R A S. Platelet-neutrophil interaction and thromboinflammation in diabetes:considerations for novel therapeutic approaches[J]. J Am Heart Assoc, 2022, 11(20):e027071. DOI URL
[29]	Lappegård K T, Fung M, Bergseth G, et al. Effect of complement inhibition and heparin coating on artificial surface-induced leukocyte and platelet activation[J]. Ann Thorac Surg, 2004, 77(3):932-941. PMID
[30]	Loeven M A, Maciej-hulme M L, Yanginlar C, et al. Selective binding of heparin/heparan sulfate oligosaccharides to factor H and factor H-related proteins:therapeutic potential for C3 glomerulopathies[J]. Front Immunol, 2021, 12:676662. DOI URL
[31]	Blatt A Z, Saggu G, Cortes C, et al. Factor H C-terminal domains are critical for regulation of platelet/granulocyte aggregate formation[J]. Front Immunol, 2017, 8:1586. DOI PMID
[32]	Wang Y, Miao Y, Gong K, et al. Plasma complement protein C3a level was associated with abdominal aortic calcification in patients on hemodialysis[J]. J Cardiovasc Transl Res, 2019, 12(5):496-505. DOI PMID
[33]	吴嘉, 汪俊军. 补体系统在动脉粥样硬化性心血管疾病中的研究与应用[J]. 中华检验医学杂志, 2020, 43(9):855-859.
[34]	Li H, Sun K, Zhao R, et al. Inflammatory biomarkers of coronary heart disease[J]. Front Biosci(Schol Ed), 2018, 10(1):185-196.
[35]	Wenzel U O, Kemper C, Bode M. The role of complement in arterial hypertension and hypertensive end organ damage[J]. Br J Pharmacol, 2021, 178(14):2849-2862. DOI URL
[36]	Zhang X, Yin J, Shao K, et al. High serum complement component C4 as a unique predictor of unfavorable outcomes in diabetic stroke[J]. Metab Brain Dis, 2021, 36(8):2313-2322. DOI PMID
[37]	Rawish E, Sauter M, Sauter R, et al. Complement,inflammation and thrombosis[J]. Br J Pharmacol, 2021, 178(14):2892-2904. DOI URL
[38]	Yerigeri K, Kadatane S, Mongan K, et al. Atypical hemolytic-uremic syndrome:genetic basis,clinical manifestations,and a multidisciplinary approach to management[J]. J Multidiscip Healthc, 2023, 16:2233-2249. DOI PMID
[39]	Fakhouri F, Schwotzer N, Frémeaux-bacchi V. How I diagnose and treat atypical hemolytic uremic syndrome[J]. Blood, 2023, 141(9):984-995. DOI URL
[40]	王乐宇, 胡青林, 陈苗, 等. 依库珠单抗治疗溶血性阵发性睡眠性血红蛋白尿症的中国真实世界研究[J]. 中华血液学杂志, 2024, 45(2):184-189.
[41]	Antonucci L, Thurman J M, Vivarelli M. Complement inhibitors in pediatric kidney diseases:new therapeutic opportunities[J]. Pediatr Nephrol, 2024, 39(5):1387-1404. DOI
[42]	Dai X, Ma Y, Lin Q, et al. Clinical features and management of atypical hemolytic uremic syndrome patient with DGKE gene variants:a case report[J]. Front Pediatr, 2023, 11:1162974. DOI URL
[43]	Szlendak U, Budziszewska B, Spychalska J, et al. Paroxysmal nocturnal hemoglobinuria:advances in the understanding of pathophysiology,diagnosis,and treatment[J]. Pol Arch Intern Med, 2022, 132(6):16271.
[44]	Kokoris S, Polyviou A, Evangelidis P, et al. Thrombosis in paroxysmal nocturnal hemoglobinuria(PNH):from pathogenesis to treatment[J]. Int J Mol Sci, 2024, 25(22):12104. DOI URL
[45]	李丽燕, 付蓉. 阵发性睡眠性血红蛋白尿症诊断与治疗中国指南(2024年版)解读[J]. 中华血液学杂志, 2024, 45(12):1071-1077.
[46]	Brodsky R A. How I treat paroxysmal nocturnal hemoglobinuria[J]. Blood, 2021, 137(10):1304-1309. DOI PMID