1.上海中医药大学交叉科学研究院(上海 201203)
扫 描 看 全 文
吴娇,王沛纯,刘璇.新型冠状病毒肺炎患者中的凝血功能异常及其可能机制和治疗策略[J].上海中医药大学学报,2022,36(06):90-100.
WU Jiao,WANG Peichun,LIU Xuan.Coagulopathy in patients with COVID⁃19 and its possible mechanisms as well as treatment strategies[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(06):90-100.
吴娇,王沛纯,刘璇.新型冠状病毒肺炎患者中的凝血功能异常及其可能机制和治疗策略[J].上海中医药大学学报,2022,36(06):90-100. DOI: 10.16306/j.1008-861x.2022.06.014.
WU Jiao,WANG Peichun,LIU Xuan.Coagulopathy in patients with COVID⁃19 and its possible mechanisms as well as treatment strategies[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(06):90-100. DOI: 10.16306/j.1008-861x.2022.06.014.
新型冠状病毒肺炎(COVID-19)是由新型冠状病毒导致的一种急性传染性疾病,除肺部出现损伤外,患者全身的多个器官和系统都可能受到影响。其中,值得重视的病理特征之一是凝血功能的异常,在COVID-19重症及危重症患者中普遍出现了凝血功能异常,主要表现为D-二聚体以及纤维蛋白原显著上升等。凝血功能的异常以及血栓的形成还可导致血小板的数量显著降低等后果。已有临床研究结果显示,凝血功能异常与COVID-19患者的危重率和病死率密切相关。本文对COVID-19患者中凝血功能异常及其可能的机制和治疗策略进行综述,以期为COVID-19及其他类似炎症性疾病的治疗提供参考。
Coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2), which may affect multiple organs and systems throughout the body in addition to lung damage. Among them, one of the notable pathological features is coagulopathy, which is commonly found in patients with severe and critical COVID-19, mainly characterized by the significant increase in D-dimer and fibrinogen. Coagulopathy and the formation of thrombosis could also lead to a significant reduction in the number of platelets and other consequences. Clinical studies have shown that coagulopathy is closely related to the severity and mortality rates of COVID-19 patients. In this review, coagulopathy and its possible mechanisms as well as treatment strategies in patients with COVID-19 were reviewed to provide reference for the treatment of COVID-19 and other similar inflammatory diseases.
COVID-19凝血异常D-二聚体血栓血小板
COVID-19coagulopathyD-dimerthrombusplatelet
CHEN B,TIAN E K,HE B,et al. Overview of lethal human coronaviruses[J]. Signal Transduct Target Ther,2020,5(1):89.
WANG D,HU B,HU C,et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China[J]. JAMA,2020,323(11):1061-1069.
GUPTA A,MADHAVAN M V,SEHGAL K,et al. Extrapulmonary manifestations of COVID-19[J]. Nat Med,2020,26(7):1017-1032.
PERICO L,BENIGNI A,CASIRAGHI F,et al. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19[J]. Nat Rev Nephrol,2021,17(1):46-64.
NÄGELE M P,HAUBNER B,TANNER F C,et al. Endothelial dysfunction in COVID-19: Current findings and therapeutic implications[J]. Atherosclerosis,2020,314:58-62.
梅恒,胡豫. 新型冠状病毒肺炎(COVID-19)患者出凝血功能障碍病因分析及诊治策略[J]. 中华血液学杂志,2020, 41(3): 185-191.
王兆钺,余自强,殷杰. 新型冠状病毒肺炎并发的凝血障碍[J]. 血栓与止血学,2021, 27(3): 361-364.
周澧,秦川. 2019新型冠状病毒肺炎凝血异常机制与中医血瘀证候[J]. 中国比较医学杂志,2022, 32(1): 89-96.
TEN V S,PINSKY D J. Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction[J]. Curr Opin Crit Care, 2002, 8(3): 242-250.
国家卫生健康委员会办公厅,国家中医药管理局办公室. 关于印发新型冠状病毒肺炎诊疗方案(试行第九版)的通知[EB/OL].(2022-03-14)[2022-10-09]. http://www.gov.cn/zhengce/zhengceku/2022-03/15/content_5679257.htmhttp://www.gov.cn/zhengce/zhengceku/2022-03/15/content_5679257.htm.
邹海,李慧洋,张有志,等. 新型冠状病毒感染与凝血功能关系的研究进展[J]. 医药导报,2020, 39(4): 448-451.
FURIE B,FURIE B C. Mechanisms of thrombus formation[J]. N Engl J Med, 2008, 359(9): 938-949.
SANG Y,ROEST M,D E LAAT B,et al. Interplay between platelets and coagulation[J]. Blood Rev, 2021, 46: 100733.
THACHIL J, TANG N, GANDO S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19[J]. J Thromb Haemost, 2020, 18(5): 1023-1026.
KOSSMANN S, LAGRANGE J, JÄCKEL S, et al. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension[J]. Sci Transl Med, 2017, 9(375): eaah4923.
ANDERSON J A, WEITZ J I. Hypercoagulable states[J]. Crit Care Clin, 2011, 27(4): 933-952,Ⅶ.
KRAUSE D S. TFPI blockade:removing coagulation’s brakes[J]. Blood, 2019, 134(22): 1884-1885.
WEITZ J I, FREDENBURGH J C, EIKELBOOM J W. A Test in Context: D-Dimer[J]. J Am Coll Cardiol, 2017, 70(19): 2411-2420.
WOOL G D, MILLER J L. The Impact of COVID-19 Disease on Platelets and Coagulation[J]. Pathobiology, 2021, 88(1): 15-27.
LEVI M, THACHIL J, IBA T, et al. Coagulation abnormalities and thrombosis in patients with COVID-19[J]. The Lancet Haematology, 2020, 7(6): e438-e440.
TANG N, LI D, WANG X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia[J]. J Thromb Haemost, 2020, 18(4): 844-847.
ZHANG L, YAN X, FAN Q, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19[J]. J Thromb Haemost, 2020, 18(6): 1.
IBA T, LEVY J H, LEVI M,et al. Coagulopathy in COVID-19[J]. J Thromb Haemost, 2020, 18(9): 2103-2019.
KWEE R M,ADAMS H J A,KWEE T C. Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: meta-analysis[J]. Eur Radiol, 2021, 31(11): 8168-8186.
FUSS C,PALMAZ J C,SPRAGUE E A. Fibrinogen: Structure, Function, and Surface Interactions[J]. J Vasc Interv Radiol, 2001, 12(6): 677-682.
黄劲,尹小建,黄芳. 纤维蛋白原相关药物研究进展[J]. 药学研究,2019, 38(3): 167-171.
ROSTAMI M, KHOSHNEGAH Z, MANSOURITORGHABEH H. Hemostatic System (Fibrinogen Level, D-Dimer, and FDP) in Severe and Non-Severe Patients With COVID-19: A Systematic Review and Meta-Analysis[J].Clin Appl Thromb Hemost, 2021, 27: 10760296211010973.
UNDAS A, ARIENS R A. Fibrin clot structure and function:a role in the pathophysiology of arterial and venous thromboembolic diseases[J]. Arterioscler Thromb Vasc Biol, 2011, 31(12): e88-e99.
GUEVARA-NORIEGA K A, LUCAR-LOPEZ G A, NUÑEZ G, et al. Coagulation Panel in Patients with SARS-CoV2 Infection (COVID-19)[J]. Ann Clin Lab Sci, 2020, 50(3): 295-298.
AL-SAMKARI H, KARP LEAF R S, DZIK W H, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection[J]. Blood, 2020, 136(4): 489-500.
ZHANG X, YANG X, JIAO H, et al. Coagulopathy in patients with COVID-19: a systematic review and meta-analysis[J]. Aging (Albany NY), 2020, 12(24): 24535-24551.
JIN X, DUAN Y, BAO T, et al. The values of coagulation function in COVID-19 patients[J]. PLoS One, 2020, 15(10): e0241329.
BACHLER M, BÖSCH J, STÜRZEL D P,et al. Impaired fibrinolysis in critically ill COVID-19 patients[J]. Br J Anaesth, 2021, 126(3): 590-598.
LI M,DONG Y,WANG H,et al. Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19[J]. Nutr Metab Cardiovasc Dis, 2020, 30(7): 1061-1067.
HADID T,KAFRI Z,AL-KATIB A. Coagulation and anticoag-ulation in COVID-19[J]. Blood Rev, 2021, 47: 100761.
侯蕊,景永宏. 血浆纤维蛋白单体、纤维蛋白降解产物和D二聚体水平的变化在急性白血病中的诊断价值[J]. 血栓与止血学,2021, 27(2): 313-314.
HAN H,YANG L,LIU R,et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection[J]. Clin Chem Lab Med, 2020, 58(7): 1116-1120.
LAZZARONI M G,PIANTONI S, MASNERI S, et al. Coagulation dysfunction in COVID-19: The interplay between inflammation, viral infection and the coagulation system[J]. Blood Rev, 2021, 46: 100745.
PORFIDIA A, VALERIANI E, POLA R,et al. Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis[J]. Thromb Res, 2020, 196: 67-74.
WAN S, XIANG Y, FANG W,et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing[J]. J Med Virol, 2020, 92(7): 797-806.
汪小五,高勇,武东. 凝血指标对COVID-19病情发展的预测价值[J]. 检验医学,2021, 36(1): 57-59.
LUO H C, YOU C Y, LU S W, et al. Characteristics of coagulation alteration in patients with COVID-19[J]. Ann Hematol, 2021, 100(1): 45-52.
ZHANG S, LIU Y, WANG X, et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19[J]. J Hematol Oncol,2020, 13(1): 120.
白欢,沈玲,陈星,等. PT、DD和PLT在新型冠状病毒肺炎重症患者预后评估及基于SIC积分系统指导抗凝治疗的价值研究[J]. 中华检验医学杂志,2020, 43(12): 1205-1211.
潘云虎,陈光,黄奕江,等. COVID-19患者凝血状况及对预后的影响研究[J]. 人民军医,2021, 64(11): 1086-1088.
CHEN N, ZHOU M, DONG X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study[J]. The Lancet, 2020, 395(10223): 507-513.
UZUN G, PELZL L, SINGH A, et al. Immune-Mediated Platelet Activation in COVID-19 and Vaccine-Induced Immune Thrombotic Thrombocytopenia[J]. Front Immunol, 2022, 13: 837629.
MADIAN A, ELIWA A, ABDALLA H, et al. Aspartate transferase-to-platelet ratio index-plus: A new simplified model for predicting the risk of mortality among patients with COVID-19[J]. World J Gastroenterol, 2022, 28(16): 1671-1680.
ERCAN H, SCHROTTMAIER W C, PIRABE A, et al. Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5[J]. Front Cardiovasc Med, 2021, 8: 779073.
姜慧欣,黄学涵,林果,等. 细胞因子风暴在2019新型冠状病毒肺炎肺损伤中的作用[J]. 临床与病理杂志,2022, 42(2): 462-471.
STIRLING D, HANNANT W A, LUDLAM C A. Transcriptional activation of the factor Ⅷ gene in liver cell lines by interleukin-6[J]. Thromb Haemost, 1998, 79(1): 74-78.
DEANFIELD J E, HALCOX J P, RABELINK T J. Endothelial function and dysfunction:testing and clinical relevance[J]. Circulation, 2007, 115(10): 1285-1295.
AHMED S, ZIMBA O, GASPARYAN A Y. Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad[J]. Clin Rheumatol, 2020, 39(9): 2529-2543.
QIN Z, LIU F, BLAIR R, et al. Endothelial cell infection and dysfunction, immune activation in severe COVID-19[J]. Theranostics, 2021, 11(16): 8076-8091.
HANFF T C, MOHAREB A M, GIRI J, et al. Thrombosis in COVID-19[J]. Am J Hematol, 2020, 95(12): 1578-1589.
VERSTEEG H H, HEEMSKERK J W, LEVI M, et al. New fundamentals in hemostasis[J]. Physiol Rev, 2013, 93(1): 327-358.
CHAO Y, REBETZ J, BLACKBERG A, et al. Distinct phenotypes of platelet, monocyte, and neutrophil activation occur during the acute and convalescent phase of COVID-19[J]. Platelets, 2021, 32(8): 1092-1102.
KOUPENOVA M, CORKREY H A, VITSEVA O, et al. SARS-CoV-2 Initiates Programmed Cell Death in Platelets[J]. Circ Res, 2021, 129(6): 631-646.
MANNE B K, DENORME F, MIDDLETON E A, et al. Platelet gene expression and function in patients with COVID-19[J]. Blood, 2020, 136(11): 1317-1329.
CAMPBELL R A, BOILARD E,RONDINA M T. Is there a role for the ACE2 receptor in SARS-CoV-2 interactions with platelets?[J]. J Thromb Haemost, 2021, 19(1): 46-50.
ZAID Y, PUHM F, ALLAEYS I, et al. Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19[J]. Circ Res, 2020, 127(11): 1404-1418.
HOTTZ E D, AZEVEDO-QUINTANILHA I G, PALHINHA L, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19[J]. Blood, 2020, 136(11): 1330-1341.
TAFAZOLI A,ANIL KUMAR S, OTHMAN M. Thrombocyto-pathy vs Platelet hyper-reactivity in COVID-19: diverse pathologies, disease outcomes and therapeutic implications[J]. Platelets,2022, 33(1): 48-53.
KHALID A, SULIMAN A M, ABDALLAH E I, et al. Influence of COVID-19 on lymphocyte and platelet parameters among patients admitted to intensive care unit and emergency[J]. Eur Rev Med Pharmacol Sci, 2022, 26(7): 2579-2585.
JEVTIC S D, NAZY I. The COVID Complex: A Review of Platelet Activation and Immune Complexes in COVID-19[J]. Front Immunol, 2022, 13: 807934.
SUN S, URBANUS R T, TEN CATE H, et al. Platelet Activation Mechanisms and Consequences of Immune Thrombocytopenia[J]. Cells, 2021, 10(12): 3386.
GOLDMAN M, HERMANS C. Thrombotic thrombocytopenia associated with COVID-19 infection or vaccination: Possible paths to platelet factor 4 autoimmunity[J]. PLoS Med, 2021, 18(5): e1003648.
万雨薇,王沛纯,葛广波,等. 清肺排毒汤促进巨核细胞分化和血小板生成的作用研究[J]. 上海中医药大学学报,2021, 35(5): 52-60.
MEI H, LUO L, HU Y. Thrombocytopenia and thrombosis in hospitalized patients with COVID-19[J]. J Hematol Oncol, 2020, 13(1): 161.
LEENTJENS J,VAN HAAPS T F,WESSELS P F,et al. COVID-19-associated coagulopathy and antithrombotic agents-lessons after 1 year[J]. Lancet Haematol, 2021, 8(7): e524-e533.
GUPTA N, ZHAO Y Y, EVANS C E. The stimulation of thrombosis by hypoxia[J]. Thromb Res, 2019, 181: 77-83.
TSANG H F,CHAN L W C,CHO W C S,et al. An update on COVID-19 pandemic: the epidemiology, pathogenesis, prevention and treatment strategies[J]. Expert Rev Anti Infect Ther, 2021, 19(7): 877-888.
ZHAO J, TIAN S, LU D, et al. Systems pharmacological study illustrates the immune regulation, anti-infection,anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19[J]. Phytomedicine, 2021, 85: 153315.
BERTOLETTI L, BIKDELI B, ZUILY S, et al. Thrombopro-phylaxis strategies to improve the prognosis of COVID-19[J]. Vascul Pharmacol, 2021, 139: 106883.
LIU X,LI Z,LIU S,et al. Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction[J/OL]. medRxiv,2020[2022-10-28]. https://www.medrxiv.org/content/10.1101/2020.02.27.20027557v1https://www.medrxiv.org/content/10.1101/2020.02.27.20027557v1.
GóMEZ-MESA J E, GALINDO-CORAL S, MONTES M C, et al. Thrombosis and Coagulopathy in COVID-19[J]. Current Problems in Cardiology, 2021, 46(3): 100742.
WHYTE C S, MORROW G B, MITCHELL J L,et al. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19[J]. J Thromb Haemost, 2020, 18(7): 1548-1555.
ALHARTHY A, FAQIHI F, PAPANIKOLAOU J, et al. Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism[J]. Am J Emerg Med, 2021, 41: 261.e1-261.e3.
KOSANOVIC D, YAROSHETSKIY A I, TSAREVA N A, et al. Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale[J]. Int J Infect Dis,2021, 104: 108-110.
曾瑾,李莉,尹竹君,等. 中药复方治疗新型冠状病毒肺炎(COVID-19)合理用药分析[J]. 中药药理与临床,2020, 36(2): 2-11.
赵裕沛,黄宝驹,朱益敏. 化瘀法在新型冠状病毒肺炎中应用初探[J]. 世界科学技术-中医药现代化,2021, 23(4): 1251-1256.
王国玉,岳淼,张伟,等. 凉血活血法防治新型冠状病毒肺炎的中医理论分析与治验[J]. 江苏中医药,2021, 53(1): 46-49.
傅晓燕,王卫星,张焰理. 清瘟败毒饮对脓毒症患者凝血功能的影响[J]. 安徽中医学院学报,2009, 28(4): 30-32.
杨玉莹,窦晓鑫,王方园,等. 抗新型冠状病毒肺炎“三药三方”之中医理论探讨[J]. 天津中医药,2021, 38(6): 700-705.
REN W,MA Y,WANG R,et al. Research Advance on Qingfei Paidu Decoction in Prescription Principle,Mechanism Analysis and Clinical Application[J]. Front Pharmacol, 2020, 11: 589714.
孟军华,何阳,陈茜,等. 清肺排毒汤治疗普通型/重型新型冠状病毒肺炎的回顾性研究[J]. 中国医院药学杂志,2020, 40(20): 2152-2157.
HUERTAS A, MONTANI D,SAVALE L, et al. Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?[J]. Eur Respir J, 2020, 56(1): 2001634.
ASAKURA H, OGAWA H. COVID-19-associated coagulopathy and disseminated intravascular coagulation[J]. Int J Hematol,2021, 113(1): 45-57.
PONTI G, MACCAFERRI M, RUINI C, et al. Biomarkers associated with COVID-19 disease progression [J]. Crit Rev Clin Lab Sci, 2020, 57(6): 389-399.
0
Views
1085
下载量
0
CSCD
0
CNKI被引量
Publicity Resources
Related Articles
Related Author
Related Institution