|
|
脓毒症性凝血病发病机制的研究进展
|
Abstract:
脓毒症(sepsis)是危重症患者常见的死亡原因。在脓毒症中，促凝血途径和抗凝途径之间的平衡被打破，导致全身凝血酶生成、抗凝活性受损和纤维蛋白溶解抑制，称为脓毒症性凝血病(sepsis-induced coagulopathy, SIC)。SIC是脓毒症的一种常见的并发症，见于24%的脓毒症患者和66%的脓毒性休克患者，并且通常与不良临床结局和高死亡率有关。SIC发病机制复杂，目前尚未完全阐明，最近的临床研究对SIC的分子发病机制产生了新的见解，本文就脓毒症性凝血病的发病机制进行综述。
Sepsis is a common cause of death in critically ill patients. In sepsis, the balance between procoagulant and anticoagulant pathways is disrupted, leading to systemic thrombin generation, impaired anticoagulant activity, and inhibition of fibrinolysis, a condition known as sepsis-induced coagulopathy (SIC). SIC is a common complication of sepsis, affecting 24% of sepsis patients and 66% of those with septic shock, and is usually associated with poor clinical outcomes and high mortality rates. The pathogenesis of SIC is complex and not yet fully understood. Recent clinical studies have provided new insights into the molecular mechanisms of SIC. This review aims to summarize the pathogenesis of sepsis-induced coagulopathy.
| [1] | Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., et al. (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 801-810. https://doi.org/10.1001/jama.2016.0287 |
| [2] | Fleischmann-Struzek, C., Mellhammar, L., Rose, N., Cassini, A., Rudd, K.E., Schlattmann, P., et al. (2020) Incidence and Mortality of Hospital-and ICU-Treated Sepsis: Results from an Updated and Expanded Systematic Review and Meta-Analysis. Intensive Care Medicine, 46, 1552-1562. https://doi.org/10.1007/s00134-020-06151-x |
| [3] | Giustozzi, M., Ehrlinder, H., Bongiovanni, D., Borovac, J.A., Guerreiro, R.A., Gąsecka, A., et al. (2021) Coagulopathy and Sepsis: Pathophysiology, Clinical Manifestations and Treatment. Blood Reviews, 50, Article 100864. https://doi.org/10.1016/j.blre.2021.100864 |
| [4] | Schmoch, T., Möhnle, P., Weigand, M.A., Briegel, J., Bauer, M., Bloos, F., et al. (2023) The Prevalence of Sepsis-Induced Coagulopathy in Patients with Sepsis—A Secondary Analysis of Two German Multicenter Randomized Controlled Trials. Annals of Intensive Care, 13, Article No. 3. https://doi.org/10.1186/s13613-022-01093-7 |
| [5] | Tanaka, C., Tagami, T., Kudo, S., Takehara, A., Fukuda, R., Nakayama, F., et al. (2021) Validation of Sepsis-Induced Coagulopathy Score in Critically Ill Patients with Septic Shock: Post Hoc Analysis of a Nationwide Multicenter Observational Study in Japan. International Journal of Hematology, 114, 164-171. https://doi.org/10.1007/s12185-021-03152-4 |
| [6] | Iba, T., Helms, J. and Levy, J.H. (2024) Sepsis-Induced Coagulopathy (SIC) in the Management of Sepsis. Annals of Intensive Care, 14, Article No. 148. https://doi.org/10.1186/s13613-024-01380-5 |
| [7] | Williams, B., Zou, L., Pittet, J. and Chao, W. (2024) Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesthesia & Analgesia, 138, 696-711. https://doi.org/10.1213/ane.0000000000006888 |
| [8] | Østerud, B. and Bjørklid, E. (2001) The Tissue Factor Pathway in Disseminated Intravascular Coagulation. Seminars in Thrombosis and Hemostasis, 27, 605-618. https://doi.org/10.1055/s-2001-18866 |
| [9] | Rosen, E.D., Chan, J.C.Y., Idusogie, E., Clotman, F., Vlasuk, G., Luther, T., et al. (1997) Mice Lacking Factor VII Develop Normally but Suffer Fatal Perinatal Bleeding. Nature, 390, 290-294. https://doi.org/10.1038/36862 |
| [10] | Bugge, T.H., Xiao, Q., Kombrinck, K.W., Flick, M.J., Holmbäck, K., Danton, M.J., et al. (1996) Fatal Embryonic Bleeding Events in Mice Lacking Tissue Factor, the Cell-Associated Initiator of Blood Coagulation. Proceedings of the National Academy of Sciences, 93, 6258-6263. https://doi.org/10.1073/pnas.93.13.6258 |
| [11] | Chen, F., Zou, L., Williams, B. and Chao, W. (2021) Targeting Toll-Like Receptors in Sepsis: From Bench to Clinical Trials. Antioxidants & Redox Signaling, 35, 1324-1339. https://doi.org/10.1089/ars.2021.0005 |
| [12] | Hakkim, A., Fuchs, T.A., Martinez, N.E., Hess, S., Prinz, H., Zychlinsky, A., et al. (2010) Activation of the Raf-MEK-ERK Pathway Is Required for Neutrophil Extracellular Trap Formation. Nature Chemical Biology, 7, 75-77. https://doi.org/10.1038/nchembio.496 |
| [13] | Delabranche, X., Helms, J. and Meziani, F. (2017) Immunohaemostasis: A New View on Haemostasis during Sepsis. Annals of Intensive Care, 7, Article No. 117. https://doi.org/10.1186/s13613-017-0339-5 |
| [14] | Nickel, K.F. and Renné, T. (2012) Crosstalk of the Plasma Contact System with Bacteria. Thrombosis Research, 130, S78-S83. https://doi.org/10.1016/j.thromres.2012.08.284 |
| [15] | Fuchs, T.A., Brill, A., Duerschmied, D., Schatzberg, D., Monestier, M., Myers, D.D., et al. (2010) Extracellular DNA Traps Promote Thrombosis. Proceedings of the National Academy of Sciences, 107, 15880-15885. https://doi.org/10.1073/pnas.1005743107 |
| [16] | Laridan, E., Martinod, K. and De Meyer, S. (2019) Neutrophil Extracellular Traps in Arterial and Venous Thrombosis. Seminars in Thrombosis and Hemostasis, 45, 86-93. https://doi.org/10.1055/s-0038-1677040 |
| [17] | Swystun, L.L. and Liaw, P.C. (2016) The Role of Leukocytes in Thrombosis. Blood, 128, 753-762. https://doi.org/10.1182/blood-2016-05-718114 |
| [18] | Sniecinski, R.M., Welsby, I.J., Levi, M. and Levy, J.H. (2016) Antithrombin: Anti-Inflammatory Properties and Clinical Applications. Thrombosis and Haemostasis, 115, 712-728. https://doi.org/10.1160/th15-08-0687 |
| [19] | Wiedermann, C.J. and Römisch, J. (2002) The Anti‐Inflammatory Actions of Antithrombin—A Review. Acta Medica Austriaca, 29, 89-92. https://doi.org/10.1046/j.1563-2571.2002.02012.x |
| [20] | Chappell, D., Brettner, F., Doerfler, N., Jacob, M., Rehm, M., Bruegger, D., et al. (2014) Protection of Glycocalyx Decreases Platelet Adhesion after Ischaemia/Reperfusion. European Journal of Anaesthesiology, 31, 474-481. https://doi.org/10.1097/eja.0000000000000085 |
| [21] | Rezende, S.M., Simmonds, R.E. and Lane, D.A. (2004) Coagulation, Inflammation, and Apoptosis: Different Roles for Protein S and the Protein S-C4b Binding Protein Complex. Blood, 103, 1192-1201. https://doi.org/10.1182/blood-2003-05-1551 |
| [22] | D’Angelo, A., Vigano-D’Angelo, S., Esmon, C.T. and Comp, P.C. (1988) Acquired Deficiencies of Protein S. Protein S Activity during Oral Anticoagulation, in Liver Disease, and in Disseminated Intravascular Coagulation. Journal of Clinical Investigation, 81, 1445-1454. https://doi.org/10.1172/jci113475 |
| [23] | Esmon, N.L., Owen, W.G. and Esmon, C.T. (1982) Isolation of a Membrane-Bound Cofactor for Thrombin-Catalyzed Activation of Protein C. Journal of Biological Chemistry, 257, 859-864. https://doi.org/10.1016/s0021-9258(19)68276-1 |
| [24] | de Wouwer, M.V., Collen, D. and Conway, E.M. (2004) Thrombomodulin-Protein C-EPCR System: Integrated to Regulate Coagulation and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1374-1383. https://doi.org/10.1161/01.atv.0000134298.25489.92 |
| [25] | Ikezoe, T. (2015) Thrombomodulin/Activated Protein C System in Septic Disseminated Intravascular Coagulation. Journal of Intensive Care, 3, Article No. 1. https://doi.org/10.1186/s40560-014-0050-7 |
| [26] | Lin, S., Wang, Y., Lin, H., Lee, K., Huang, C., Liu, C., et al. (2008) Serum Thrombomodulin Level Relates to the Clinical Course of Disseminated Intravascular Coagulation, Multiorgan Dysfunction Syndrome, and Mortality in Patients with Sepsis. Critical Care Medicine, 36, 683-689. https://doi.org/10.1097/ccm.0b013e31816537d8 |
| [27] | Scarlatescu, E., Tomescu, D. and Arama, S.S. (2016) Sepsis-Associated Coagulopathy. The Journal of Critical Care Medicine, 2, 156-163. https://doi.org/10.1515/jccm-2016-0024 |
| [28] | Zeerleder, S., Schroeder, V., Hack, C.E., Kohler, H.P. and Wuillemin, W.A. (2006) TAFI and PAI-1 Levels in Human Sepsis. Thrombosis Research, 118, 205-212. https://doi.org/10.1016/j.thromres.2005.06.007 |
| [29] | Mavrommatis, A.C., Theodoridis, T., Economou, M., Kotanidou, A., El Ali, M., Christopoulou-Kokkinou, V., et al. (2001) Activation of the Fibrinolytic System and Utilization of the Coagulation Inhibitors in Sepsis: Comparison with Severe Sepsis and Septic Shock. Intensive Care Medicine, 27, 1853-1859. https://doi.org/10.1007/s00134-001-1139-8 |
