COVID-19’da Koagülopati
Synopsis
In COVID-19 infection, coagulopathy and thromboembolic events are key characteristic features directly associated with disease severity, clinical progression, and poor prognosis. The uncontrolled cytokine storm induced by the virus causes vascular endothelial damage, tissue factor expression, complement activation, platelet and leukocyte activation, and disruption of natural anticoagulant mechanisms, significantly increasing the risk of pulmonary microthrombi and systemic thrombosis. These localized immuno-inflammatory and hemostatic disorders in the pulmonary vasculature exacerbate hypoxia, ARDS, and multiple organ failure. In severe COVID-19 patients, excessive elevation of D-dimer levels, prolongation of prothrombin time (PT), thrombocytopenia, and hypofibrinogenemia that may develop in late stages are strongly associated with intensive care requirement and high in-hospital mortality. COVID-19-associated coagulopathy differs from classic DIC, thrombotic microangiopathy, and hemophagocytic lymphohistiocytosis syndromes, as it does not present a true consumption coagulopathy, severe bleeding events are rare, and it points to localized pulmonary intravascular coagulation rather than systemic DIC. Thromboprophylaxis with low-molecular-weight heparin (LMWH) is recommended in management; heparin is reported to reduce mortality and pulmonary coagulopathy not only via its anticoagulant effect but also by binding to the viral spike protein and preventing cell entry. However, considering the risks of gastrointestinal bleeding and heparin-induced thrombocytopenia, dynamic monitoring of coagulation parameters such as D-dimer, PT, APTT, platelets, and fibrinogen, along with optimizing treatment based on the pathophysiological status, is recommended.
References
(WHO2021) WHO Coronavirus Disease (COVID-19) Dashboard Erişim:5 Mart 2021 https://covid19.who.int/table
Kamel A, Sobhy M, Magdy N, Sabry N, (2020). Anticoagulation outcomes in hospitalized Covid‐19 patients: A systematic review and meta‐analysis of case‐control and cohort studies. J.Med. doi:10.1002/rmv.2180
Lodigiani C, Lapichino G, Carenzo L, Venous and arterial thromboembolic complications in COVID‐19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020 Jul;191:9-14. doi: 10.1016/j.thromres.2020.04.024.
Jose RJ, Manuel A, COVID‐19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020;8(6): e46‐e47. https://doi.org/10.1016/S2213-2600(20)30216-2.
Szegedi I, Orbán K, Csiba L, & Bagoly Z (2020). Stroke as a Potential Complication of COVID-19-Associated Coagulopathy: A Narrative and Systematic Review of the Literature. J. Clin. Medicine,2020; 9(10), 3137.doi:10.3390/jcm9103137
FeiY, Tang N, Liu H, & Cao W.(2020). Coagulation dysfunction: A hallmark in COVID-19. 2020 Oct 1;144(10):1223-1229. Archives of Path. & Lab. Medicine.doi:10.5858/arpa.2020-0324-sa
Paliogiannis P, Mangoni A, Dettori P (2020). D-Dimer Concentrations and COVID-19 Severity: A Systematic Review and Meta-Analysis. Frontiers in Public Health, 8Front Public Health 2020 Aug 4;8:432. doi: 10.3389/fpubh.2020.00432.
Baris G, Adem A, Omer B Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis J Emerg Med 2021 Jan;39:173-179. doi: 10.1016/j.ajem.2020.09.018.
Juan G, Stephania C, Maria M Curr Probl Cardiol .Thrombosis and Coagulopathy in COVID-19: 100742. Volume 46, Issue 3, March 2021, 100742 doi: 10.1016 / j.cpcardiol.2020.100742
Amerıcan Society Of Hematology (2021) Erişim: 5 Mart 2021 https://www.hematology.org/covid19/covid-19-and-coagulopathy
Lin J, Yan H, Chen H, He C, COVID‐19 and Coagulation Dysfunction in Adults: A Systematic Review and Meta‐analysis. J. Med. Virology. 2020;1–11. doi: 10.1002/jmv.26346.
Moreno G, Carbonell R, Bodí M, & Rodríguez A (2020). Revisión sistemática sobre la utilidad pronóstica del dímero-D, coagulación intravascular diseminada y tratamiento anticoagulante en pacientes graves con COVID-19. Medicina Intensiva.doi:10.1016/j.medin.2020.06.006
Xiaolin Z , Xue Y, Hongmei J Coagulopathy in patients with COVID-19: a systematic review and meta-analysis Aging (Albany NY). 2020 Dec 31; 12(24): 24535–24551. doi: 10.18632/aging.104138
Becker R.C. COVID-19 update: Covid-19-associated coagulopathy. J. Thromb. Thrombolysis. 2020;50:54–67. doi: 10.1007/s11239-020-021343.
Barnes BJ, Adrover JM, Baxter A, Cools-Lartigue J Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J. Exp. Med. 2020;217:e20200652. doi: 10.1084/jem.20200652.
Szegedi I, Orbán-Kálmándi R., Csiba L, & Bagoly Z. (2020). Stroke as a Potential Complication of COVID-19-Associated Coagulopathy: A Narrative and Systematic Review of the Literature. Journal of Clinical Medicine, 9(10), 3137.doi:10.3390/jcm9103137
Ruan Q, Yang K, Wang W Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–848. doi: 10.1007/s00134-020-05991-x.
Noppacharn U, Chatphatai M, Darintr S Clin Appl Thromb Hemost Systemic Coagulopathy in Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. 2021 Jan-Dec; 27: doi: 10.1177/1076029620987629
Zhang A, Leng Y, Zhang Y, Wu K (2020). Meta-Analysis of coagulation parameters associated with disease severity and poor prognosis of COVID-19 International J.Infectious Diseases. doi:10.1016/j.ijid.2020.09.021
Lili L, Min X, Mengyi D et al. Early coagulation tests predict risk stratification and prognosis of COVID-19 Aging (Albany NY). 2020 Aug 31; 12(16): 15918–15937. doi: 10.18632/aging.103581
Wu C, Chen X, Cai Y Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020:1 10. https://doi.org/10.1001/jamainternmed.2020.0994.
Nugroho J, Wardhana A, Maghfirah I, (2020). Relationship of D‐dimer with severity and mortality in SARS‐CoV‐2 patients : A meta‐analysis. International Journal of Laboratory Hematology. doi:10.1111/ijlh.13336
Juan G.-Mesa, Stephania C, Maria M Curr Probl Cardiol Thrombosis and Coagulopathy in COVID-19 2021 Mar;46(3):100742. doi: 10.1016/j.cpcardiol.2020.100742.
Amgalan A, Othman M. Exploring possible mechanisms for COVID-19 induced thrombocytopenia: unanswered questions. J. Thromb Haemost. 2020; 18:1514–16. 10.1111/jth.14832
Spiezia L, Boscolo A, Poletto F. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure.Thromb Haemost. 2020; 120:998–1000. Doi:10.1055/s-0040-1710018
Yang X, Yu Y, Xu J. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020; 8:475–481. Doi:10.1016/S2213-2600(20)30079-5
Han H, Yang L, Liu R Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020; 58:1116–20. Doi:10.1515/cclm-2020-0188
Levi M, Meijers JC. DIC: which laboratory tests are most useful. Blood Rev. 2011; 25:33–37. Doi:10.1016/j.blre.2010.09.002
Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID‐19 related systemic thrombosis. Circulation. 2020;141:1739‐1741.doi 10.1161/CIRCULATIONAHA.120.047419
American Socıety of Hematology COVID-19 resources (2021) Erişim: 5 Mart 2021 https://www.hematology.org/covid-19
Kamath S, Lip GY. Fibrinogen: biochemistry, epidemiology and determinants. QJM. 2003;96(10):711‐729.
Muhammad A, Nooreen H, Hasan S Hematological characteristics of patients in coronavirus 19 infection: a systematic review and meta-analysis J Community Hosp Intern Med Perspect 2020 Oct 29;10(6):508-513.doi: 10.1080/20009666.2020.1808360.
Iba T, Connors M, Levy J, The coagulopathy, endotheliopathy, and vasculitis of COVID-19 Inflamm Res 2020 Dec;69(12):1181-1189. doi: 10.1007/s00011-020-01401-6.
