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Pulmonary Intravascular Coagulation Pathogenesis in COVID-19 and Treatment Recommendations

Year 2020, Volume: 3 Issue: S1, 106 - 110, 15.05.2020

Abstract

It has been recently shown that the activation of the coagulation system takes an important part in the pathogenesis of COVID-19. It has come into insight that the mortality rate is lower in patients who were administered low molecular weight heparin (LMWH) during the course of COVID-19 when compared with those who were treated without LMWH. However, we observe that the coagulopathy accompanying COVID-19 seems to be different from sepsis associated disseminated intravascular coagulation (DIC), therefore we think that organ specific coagulopathy should be better named ‘Pulmonary Intravascular CoagulationPIC’. Here we provide possible pathogenetic mechanisms underlying COVID-19 including PIC and give treatment recommendations as administration of prophylactic LMWH at patients with increased D-dimer levels at early phase, escalation to treatment dose of LMWH in case of increasing D-dimers and usage of tPA or defibrotide with evaluation of bleeding risk in patients with respiratory insufficiency. However, in what point of COVID-19 disease shall those anticoagulant/antitrombotic-thrombolytic agents used must be evaluated with further studies.

References

  • 1. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020 Apr 02. doi.org/10.1111/ jth.14821. [Epub ahead of print]
  • 2. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18(4):8447. doi: 10.1111/jth.14768.
  • 3. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;00:1-6. doi: 10.1111/jth.14817. [Epub ahead of print]
  • 4. McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Dennis McGonagle, Kassem Sharif, Anthony O’Regan, Charlie Bridgewood, The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease, Autoimmunity Reviews, 2020, 102537, ISSN 1568-9972, https://doi. org/10.1016/j.autrev.2020.102537.
  • 5. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown Q, Vander Heide RS. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv 2020 Apr 10. doi: https://doi.org/10.1101/2020.04.06.20050575.
  • 6. Tian S, Hu W,Niu, Liu H et al. Pulmonary pathology of early-phase 2019 novel Coronavirus (COVID-19) Pneumonia in two patients with lung cancer. J Thorac Oncol 2020 Feb 28. 2020 May;15(5):700-4. doi: 10.1016/j.jtho.2020.02.010. [Epub ahead of print]
  • 7. Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M; Scientific and Standardization Committee on DIC, and the Scientific and Standardization Committee on Perioperative and Critical Care of the International Society on Thrombosis and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-94.
  • 8. Thachil J, Tang J, Gando S, Falanga A, Cattaneo M, Levi M et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis 2020 March 25. doi.org/10.1111/ jth.14810.
  • 9. Türkiye Cumhuriyeti Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü, COVID-19 (SARSCoV-2 Enfeksiyonu) Rehberi 14 Nisan 2020, Ankara. Available from: URL: https://covid19bilgi. saglik.gov.tr/depo/rehberler/COVID-19_ Rehberi.pdf.
  • 10. Du L, Kao RY, Zhou Y, He Y, Zhao G, Wong C et al. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity. Biochem Biophys Res Commun.2007;359(1):174-79.
  • 11. Belen-Apak FB, Sarialioglu F. The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases? Med Hypotheses. 2020;142:109743.
  • 12. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region-Case Series [published online ahead of print, N Engl J Med. 2020 Mar 30. doi: 10.1056/ NEJMoa2004500. [Epub ahead of print]
  • 13. Moore H, Barrett CD, Moore EE, McIntyre RC, Moore PK, Talmor DS et al. Is there a role for plasminogen activator (tPA) as a novel treatment for refractory COVID-19 associated with acute respiratory distress syndrome (ARDS)? Journal of Trauma and Acute Care Surgery. 2020 Mar 2. doi: 10.1097/TA.0000000000002694 [Epub ahead of print]
  • 14. Wu Y, Wang T, Guo C, Zhang D, Ge X, Huang Z et al. Plasminogen improves lung lesions and hypoxemia in patients with COVID-19. QJM 2020 Apr 10. doi.org/10.1093/qjmed/hcaa121.
  • 15. Pescador R, Capuzzi L, Mantovani M, Fulgenzi A, Ferrero ME. Defibrotide: Properties and clinical use of an old/new drug. Vascul Pharmacol 2013;59:1-10.

COVID-19 Patogenezinde Pulmoner İntravasküler Koagülasyon ve Tedavi Önerileri

Year 2020, Volume: 3 Issue: S1, 106 - 110, 15.05.2020

Abstract

Tüm dünyayı ve ülkemizi etkisi altına alan COVID-19 hastalığının patogenezinde koagülasyon sisteminin aktive olmasının önemli rolü olduğu, dissemine intravasküler koagülasyonun (DİK) laboratuvar bulgularından D-dimer değeri yüksek olan olgulara erken dönemde düşük molekül ağırlıklı heparin (DMAH) başlanması durumunda mortalitenin azaldığı bilinmektedir. COVID-19 enfeksiyonundaki ana mekanizmalardan birinin sepsis ilişkili DİK’ten farklı organa özgü ‘Pulmoner İntravasküler Koagülasyon-PİK’ olduğunu düşünmekteyiz. Patogenetik mekanizmaları açıkladığımız derlememizde PİK erken dönemlerinde profilaktik dozda DMAH, D-dimer artışı devam etmesi durumunda tedavi dozunda DMAH, respiratuar yetmezlik gelişmesi durumunda kanama riski göz önünde bulundurularak doku plazminojen aktivatörü (tPA) ve defibrotid tedavilerinin kullanımı konusunda tedavi önerileri yer almaktadır. Bu tedavilerin COVID-19 enfeksiyonunun hangi aşamalarında kullanılmasının uygun olacağının netleştirilmesi için klinik araştırmalara gerek duyulmaktadır.

References

  • 1. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020 Apr 02. doi.org/10.1111/ jth.14821. [Epub ahead of print]
  • 2. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18(4):8447. doi: 10.1111/jth.14768.
  • 3. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;00:1-6. doi: 10.1111/jth.14817. [Epub ahead of print]
  • 4. McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Dennis McGonagle, Kassem Sharif, Anthony O’Regan, Charlie Bridgewood, The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease, Autoimmunity Reviews, 2020, 102537, ISSN 1568-9972, https://doi. org/10.1016/j.autrev.2020.102537.
  • 5. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown Q, Vander Heide RS. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv 2020 Apr 10. doi: https://doi.org/10.1101/2020.04.06.20050575.
  • 6. Tian S, Hu W,Niu, Liu H et al. Pulmonary pathology of early-phase 2019 novel Coronavirus (COVID-19) Pneumonia in two patients with lung cancer. J Thorac Oncol 2020 Feb 28. 2020 May;15(5):700-4. doi: 10.1016/j.jtho.2020.02.010. [Epub ahead of print]
  • 7. Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M; Scientific and Standardization Committee on DIC, and the Scientific and Standardization Committee on Perioperative and Critical Care of the International Society on Thrombosis and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-94.
  • 8. Thachil J, Tang J, Gando S, Falanga A, Cattaneo M, Levi M et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis 2020 March 25. doi.org/10.1111/ jth.14810.
  • 9. Türkiye Cumhuriyeti Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü, COVID-19 (SARSCoV-2 Enfeksiyonu) Rehberi 14 Nisan 2020, Ankara. Available from: URL: https://covid19bilgi. saglik.gov.tr/depo/rehberler/COVID-19_ Rehberi.pdf.
  • 10. Du L, Kao RY, Zhou Y, He Y, Zhao G, Wong C et al. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity. Biochem Biophys Res Commun.2007;359(1):174-79.
  • 11. Belen-Apak FB, Sarialioglu F. The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases? Med Hypotheses. 2020;142:109743.
  • 12. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region-Case Series [published online ahead of print, N Engl J Med. 2020 Mar 30. doi: 10.1056/ NEJMoa2004500. [Epub ahead of print]
  • 13. Moore H, Barrett CD, Moore EE, McIntyre RC, Moore PK, Talmor DS et al. Is there a role for plasminogen activator (tPA) as a novel treatment for refractory COVID-19 associated with acute respiratory distress syndrome (ARDS)? Journal of Trauma and Acute Care Surgery. 2020 Mar 2. doi: 10.1097/TA.0000000000002694 [Epub ahead of print]
  • 14. Wu Y, Wang T, Guo C, Zhang D, Ge X, Huang Z et al. Plasminogen improves lung lesions and hypoxemia in patients with COVID-19. QJM 2020 Apr 10. doi.org/10.1093/qjmed/hcaa121.
  • 15. Pescador R, Capuzzi L, Mantovani M, Fulgenzi A, Ferrero ME. Defibrotide: Properties and clinical use of an old/new drug. Vascul Pharmacol 2013;59:1-10.
There are 15 citations in total.

Details

Primary Language Turkish
Subjects Dentistry, Pharmacology and Pharmaceutical Sciences, Toxicology, Clinical Sciences
Journal Section Review
Authors

Faik Sarıalioğlu This is me

Fatma Burcu Belen Apak This is me 0000-0002-9278-6703

Publication Date May 15, 2020
Submission Date April 20, 2020
Published in Issue Year 2020 Volume: 3 Issue: S1

Cite

MLA Sarıalioğlu, Faik and Fatma Burcu Belen Apak. “COVID-19 Patogenezinde Pulmoner İntravasküler Koagülasyon Ve Tedavi Önerileri”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, vol. 3, no. S1, 2020, pp. 106-10.