open access

Ahead of print
Review Article
Submitted: 2022-09-25
Accepted: 2022-10-09
Published online: 2022-12-29
Get Citation

COVID-19-induced coagulopathy: Experience, achievements, prospects

Leonid Dubey1, Olga Dorosh12, Nataliya Dubey1, Svitlana Doan3, Olena Kozishkurt4, Oleksandr Duzenko4, Olena Kozlova12, Veronika Ievtukh1, Jerzy R. Ladny56, Michal Pruc6, Lukasz Szarpak7, Julia Pukach1
DOI: 10.5603/CJ.a2022.0123
·
Pubmed: 36588310
Affiliations
  1. Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
  2. ENT „Western Ukrainian Specialized Children’s Medical Center”, Lviv, Ukraine
  3. International European University, Kyiv, Ukraine
  4. National Medical University of Odessa, Ukraine
  5. Medical University of Bialystok, Poland
  6. Polish Society of Disaster Medicine, Warsaw, Poland
  7. Baylor College of Medicine, Houston, TX, United States

open access

Ahead of print
Review articles — COVID-19
Submitted: 2022-09-25
Accepted: 2022-10-09
Published online: 2022-12-29

Abstract

The presence of coagulopathy as part of the systemic inflammatory response syndrome is a characteristic feature of severe coronavirus disease 2019 (COVID-19). Hematological changes (increased DD-dimer, prolonged activated partial thromboplastin clotting time [APTT] and prothrombin time [PT], high fibrinogen levels) have been observed in hospitalized patients with COVID-19, which characterize the risk of thrombotic events. Against the background of COVID-19 there is endothelial dysfunction, hypoxia and pulmonary congestion, mediated by thrombosis and microvascular occlusion. Up to 71.4% of patients who died from COVID-19 had disseminated intravascular coagulation syndrome, compared with only 0.6% of survivors. The main manifestation of COVID-19-associated coagulopathy is a significant increase in DD without a decrease in platelet count or prolongation of APTT and PT, indicating increased thrombin formation and the development of local fibrinolysis. An increase in DD levels of more than 3–4 times was associated with higher in-hospital mortality. Therefore, COVID-19 requires assessment of the severity of the disease for further tactics of thromboprophylaxis. The need for continued thromboprophylaxis, or therapeutic anticoagulation, in patients after inpatient treatment for two weeks using imaging techniques to assess of thrombosis assessment.

Abstract

The presence of coagulopathy as part of the systemic inflammatory response syndrome is a characteristic feature of severe coronavirus disease 2019 (COVID-19). Hematological changes (increased DD-dimer, prolonged activated partial thromboplastin clotting time [APTT] and prothrombin time [PT], high fibrinogen levels) have been observed in hospitalized patients with COVID-19, which characterize the risk of thrombotic events. Against the background of COVID-19 there is endothelial dysfunction, hypoxia and pulmonary congestion, mediated by thrombosis and microvascular occlusion. Up to 71.4% of patients who died from COVID-19 had disseminated intravascular coagulation syndrome, compared with only 0.6% of survivors. The main manifestation of COVID-19-associated coagulopathy is a significant increase in DD without a decrease in platelet count or prolongation of APTT and PT, indicating increased thrombin formation and the development of local fibrinolysis. An increase in DD levels of more than 3–4 times was associated with higher in-hospital mortality. Therefore, COVID-19 requires assessment of the severity of the disease for further tactics of thromboprophylaxis. The need for continued thromboprophylaxis, or therapeutic anticoagulation, in patients after inpatient treatment for two weeks using imaging techniques to assess of thrombosis assessment.

Get Citation

Keywords

coronavirus disease 2019 (COVID-19) infection, COVID-19-induced coagulopathy, SARS-CoV-2

About this article
Title

COVID-19-induced coagulopathy: Experience, achievements, prospects

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Review Article

Published online

2022-12-29

Page views

271

Article views/downloads

167

DOI

10.5603/CJ.a2022.0123

Pubmed

36588310

Keywords

coronavirus disease 2019 (COVID-19) infection
COVID-19-induced coagulopathy
SARS-CoV-2

Authors

Leonid Dubey
Olga Dorosh
Nataliya Dubey
Svitlana Doan
Olena Kozishkurt
Oleksandr Duzenko
Olena Kozlova
Veronika Ievtukh
Jerzy R. Ladny
Michal Pruc
Lukasz Szarpak
Julia Pukach

References (66)
  1. Ruetzler K, Szarpak L, Filipiak K, et al. The COVID-19 pandemic — a view of the current state of the problem. Disaster Emerg Med J. 2020; 5(2): 106–107.
  2. Dzieciatkowski T, Szarpak L, Filipiak KJ, et al. COVID-19 challenge for modern medicine. Cardiol J. 2020; 27(2): 175–183.
  3. Merajikhah A, Beigi-khoozani A, Soleimani M. Risk of spreading delta coronavirus to operating room personnel after COVID-19 vaccination. Disaster Emerg Med J. 2021; 6(4): 206–207.
  4. Aguiar D, Lobrinus JA, Schibler M, et al. Inside the lungs of COVID-19 disease. Int J Legal Med. 2020; 134(4): 1271–1274.
  5. American Society of Hematology. https://www.hematology.org/covid-19/covid-19-and-coagulopathy. http://www.hematology.orgcovid-covid-and-coagulopathy (Accessed May 5, 2020).
  6. Branchford BR, Betensky M, Goldenberg NA. Pediatric issues in thrombosis and hemostasis: The how and why of venous thromboembolism risk stratification in hospitalized children. Thromb Res. 2018; 172: 190–193.
  7. Smereka J, Szarpak L, Filipiak K. Modern medicine in COVID-19 era. Disaster Emerg Med J. 2020.
  8. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020; 383(2): 120–128.
  9. Branchford BR, Mourani P, Bajaj L, et al. Risk factors for in-hospital venous thromboembolism in children: a case-control study employing diagnostic validation. Haematologica. 2012; 97(4): 509–515.
  10. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020; 18(5): 1023–1026.
  11. Zhou Y, Hou Y, Shen J, et al. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020; 6: 14.
  12. BSH Haemostatis and Thrombosis Task Force. https://b-s-h.org.uk/media/18206/dic-score-in-covid-19-pneumonia_01-04-2020.pdf (Accessed May 5, 2020).
  13. Gómez-Mesa JE, Galindo-Coral S, Montes MC, et al. Thrombosis and Coagulopathy in COVID-19. Curr Probl Cardiol. 2021; 46(3): 100742.
  14. Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020; 20(5): 269–270.
  15. Fan E, Beitler J, Brochard L, et al. COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Lancet Respir Med. 2020; 8(8): 816–821.
  16. Faustino EV, Raffini LJ. Prevention of hospital-acquired venous thromboembolism in children: a review of published guidelines. Front Pediatr. 2017; 5: 9.
  17. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; 181(2): 271–280.e8.
  18. Hou YJ, Okuda K, Edwards CE, et al. SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract. Cell. 2020; 182(2): 429–446.e14.
  19. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497–506.
  20. Jaffray J, Witmer C, O'Brien SH, et al. Peripherally inserted central catheters lead to a high risk of venous thromboembolism in children. Blood. 2020; 135(3): 220–226.
  21. Jaimes JA, Millet JK, Whittaker GR. Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site. iScience. 2020; 23(6): 101212.
  22. Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun. 2019; 10(1): 2342.
  23. Li Q, Guan X, Wu P, et al. Early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia. N Engl J Med. 2020; 382(13): 1199–1207.
  24. Li Yu, Zhang Z, Yang Li, et al. The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. iScience. 2020; 23(6): 101160.
  25. Mahajerin A, Branchford BR, Amankwah EK, et al. Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models. Haematologica. 2015; 100(8): 1045–1050.
  26. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020; 323(22): 2329–2330.
  27. Andersen KG, Rambaut A, Lipkin WI, et al. The proximal origin of SARS-CoV-2. Nat Med. 2020; 26(4): 450–452.
  28. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020; 8(4): 420–422.
  29. Szarpak L, Pruc M, Filipiak KJ, et al. Myocarditis: A complication of COVID-19 and long-COVID-19 syndrome as a serious threat in modern cardiology. Cardiol J. 2022; 29(1): 178–179.
  30. Zhang YZ, Holmes EC. A genomic perspective on the origin and emergence of SARS-CoV-2. Cell. 2020; 181(2): 223–227.
  31. Nucera G, Chirico F, Rafique Z, et al. Need to update cardiological guidelines to prevent COVID-19 related myocardial infarction and ischemic stroke. Cardiol J. 2022; 29(1): 174–175.
  32. Szarpak Ł, Nowak B, Kosior D, et al. Cytokines as predictors of COVID-19 severity: evidence from a meta-analysis. Pol Arch Intern Med. 2021; 131(1): 98–99.
  33. Song JC, Wang G, Zhang W, et al. Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19. Mil Med Res. 2020; 7(1): 19.
  34. Sungnak W, Huang Ni, Bécavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020; 26(5): 681–687.
  35. Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18(4): 844–847.
  36. Taylor F, Toh CH, Hoots K, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. J Thromb Haemost. 2017; 86(11): 1327–1330.
  37. Ruetzler K, Szarpak Ł, Ładny JR, et al. D-dimer levels predict COVID-19 severity and mortality. Kardiol Pol. 2021; 79(2): 217–218.
  38. Perico L, Benigni A, Remuzzi G. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade. Nephron. 2020; 144(5): 213–221.
  39. Pernazza A, Mancini M, Rullo E, et al. Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen. Virchows Arch. 2020; 477(5): 743–748.
  40. Ranucci M, Ballotta A, Di Dedda U, et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020; 18(7): 1747–1751.
  41. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A. 2020; 117(21): 11727–11734.
  42. Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020; 368(6494): 1016–1020.
  43. Katipoğlu B, Sönmez LÖ, Vatansev H, et al. Can hematological and biochemical parameters fasten the diagnosis of COVID-19 in emergency departments? Disaster Emerg Med J. 2020.
  44. Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020; 27(5): 1451–1454.
  45. Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020; 181(5): 1016–1035.e19.
  46. Toh CH, Hoots WK. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007; 5(3): 604–606.
  47. Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020; 94(7): e00127-20.
  48. Wang J, Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): A case series. J Thromb Haemost. 2020; 18(7): 1752–1755.
  49. Wang Y, Zhu LQ. Pharmaceutical care recommendations for antiviral treatments in children with coronavirus disease 2019. World J Pediatr. 2020; 16(3): 271–274.
  50. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809): 465–469.
  51. Xiong Mi, Liang X, Wei YD. Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Br J Haematol. 2020; 189(6): 1050–1052.
  52. Adam I, Szarpak L, Filipiak K, et al. Interferon lambda with remdesivir as a potential treatment option in COVID-19. Disaster Emerg Med J. 2020.
  53. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12(1): 8.
  54. Zumla A, Chan JFW, Azhar EI, et al. Coronaviruses — drug discovery and therapeutic options. Nat Rev Drug Discov. 2016; 15(5): 327–347.
  55. Fialek B, Pruc M, Smereka J, et al. Diagnostic value of lactate dehydrogenase in COVID-19: A systematic review and meta-analysis. Cardiol J. 2022; 29(5): 751–758.
  56. Szarpak L, Zaczynski A, Kosior D, et al. Evidence of diagnostic value of ferritin in patients with COVID-19. Cardiol J. 2020; 27(6): 886–887.
  57. Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to predict in-hospital mortality in patients with COVID-19. J Thromb Haemost. 2020; 18(6): 1324–1329.
  58. Zhou H, Chen X, Hu T, et al. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr Biol. 2020; 30(11): 2196–2203.e3.
  59. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–273.
  60. Meyer-Szary J, Jaguszewski M, Smereka J, et al. Impact of COVID-19 on pediatric out-of-hospital cardiac arrest in the Masovian region. Disaster Emerg Med J. 2021; 6(4): 183–185.
  61. Yaman E, Demirel B, Yilmaz A, et al. Retrospective evaluation of laboratory findings of suspected paediatric COVID-19 patients with positive and negative RT-PCR. Disaster Emerg Med J. 2021; 6(3): 97–103.
  62. Pruc M, Smereka J, Dzieciatkowski T, et al. Kawasaki disease shock syndrome or toxic shock syndrome in children and the relationship with COVID-19. Med Hypotheses. 2020; 144: 109986.
  63. Yaman E, Demirel B, Yilmaz A, et al. Retrospective evaluation of laboratory findings of suspected paediatric COVID-19 patients with positive and negative RT-PCR. Disaster Emerg Med J. 2021; 6(3): 97–103.
  64. Szarpak L, Filipiak KJ, Skwarek A, et al. Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19: A systematic review and meta-analysis. Cardiol J. 2022; 29(1): 33–43.
  65. Domienik-Karłowicz J, Tronina O, Lisik W, et al. The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists. Cardiol J. 2020; 27(6): 868–874.
  66. Tomaszuk-Kazberuk A, Koziński M, Domienik-Karłowicz J, et al. Pharmacotherapy of atrial fibrillation in COVID-19 patients. Cardiol J. 2021; 28(5): 758–766.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl