What is the evidence for COVID-19 causing vascular damage, disseminated intravascular coagulation (DIC), and microthrombi?

Posted on April 15, 2020 by Tomas Rapaport

Summary

There is no current evidence that COVID-19 causes significant vascular damage, however; there is evidence that it increases coagulopathy that is mainly prothrombotic with severe patients at higher risk of venous thromboembolisms and DIC.

I.   Vascular Damage

  • Experts at Thrombosis UK suggest that there is a possibility of endothelial cell activation and damage due to Cov2 binding to ACE2 receptors in the lungs (1)
  • However, there is currently no clear evidence that the virus directly attacks the lining of vessels and the most likely mechanism for any vascular damage seen in severe cases appears to be diffuse inflammation and subsequent ‘cytokine storm’ effect (2)

II.   Disseminated intravascular coagulation (DIC)

  • According to the American Society of Hematology (3): 
    • most common pattern of coagulopathy in hospitalized with COVID-19 is not DIC, but it is rather characterized by elevated fibrinogen and D-dimer levels, correlated with parallel rise in markers of inflammation (e.g. CRP)
    • Unlike the pattern seen in classic DIC from bacterial sepsis or trauma, the degree of aPTT elevation is often less than PT elevation (likely due to increased factor VIII levels), the thrombocytopenia is mild (platelet count ~100 x 10^9/L), and microangiopathy is not present
    • Still,  some patients with severe COVID-19 infection can develop a coagulopathy meeting criteria for DIC with fulminant activation of coagulation and consumption of coagulation factors
    • This is reflected by moderate to severe thrombocytopenia (platelet count <50 x 10^9/L), prolongation of the PT and aPTT, marked elevation of D-dimer, and decreased fibrinogen (< 1.0 g/L)
  • In a study from Wuhan of 138 consecutive patients, 71% of patients who died from COVID-19 met criteria for DIC, compared to 0.4% of survivors (4)
  • A related retrospective study in Wuhan of 449 consecutive severe COVID-19 patients found that 97 (21.6%) patients met criteria for Sepsis-Induced Coagulopathy (SIC), defined as a SIC score of at least 4, and considered to be an earlier phase of sepsis-induced DIC (5)

III.   Microthrombi

  • A 4 patient autopsy series, still awaiting peer review, found evidence of extensive alveolar damage with fibrin deposition outside lung parenchymal cells as well as macroscopic thrombi seen in small vessels of the lungs (6) 
  • There is evidence of an increased risk of venous and arterial thromboembolic events in COVID-19 patients admitted to ICU relative to other ICU patients (7), particularly with regards to pulmonary emboli (8) 
  • Thrombosis UK recommends that physicians consider pulmonary emboli as a likely cause of sudden oxygen desaturation, respiratory distress, and reduced blood pressure in patients with COVID-19 (1)
  • We were unable to find evidence of microthrombi present at other locations although online clinical knowledge aggregator, Life in the Fast Lane, suggests that Acute Kidney injury in patients with COVID-19 could be partly caused by microthrombi in the kidneys (9)

Questions? Comments? Does this need to be updated? Do you have valuable points to add ? Please email ask.reakt@ubc.ca.

References

  1. Obe B, Retter A, Mcclintock C. Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19 [Internet]. 2020. Available from: https://thrombosisuk.org/downloads/T&H%20and%20COVID.pdf  
  2. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Raffaela Di Napoli. Features, Evaluation and Treatment Coronavirus (COVID-19) [Internet]. Nih.gov. StatPearls Publishing; 2020 [cited 2020 Apr 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/#_article-52171_s4_
  3. Lee A. COVID-19 and Coagulopathy [Internet]. Hematology.org. 2020 [cited 2020 Apr 15]. Available from: https://www.hematology.org/covid-19/covid-19-and-coagulopathy
  4. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis [Internet]. 2020 Apr [cited 2020 Apr 15];18(4):844–7. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14768
  5. 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. Journal of Thrombosis and Haemostasis [Internet]. 2020 Mar 27 [cited 2020 Apr 15]; Available from: https://onlinelibrary.wiley.com/doi/10.1111/jth.14817
  6. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. 2020 Apr 10 [cited 2020 Apr 15]; Available from: https://www.medrxiv.org/content/10.1101/2020.04.06.20050575v1.full.pdf
  7. Lee SG, Fralick M, Sholzberg M. Coagulopathy associated with COVID-19. Canadian Medical Association Journal [Internet]. 2020 May 1 [cited 2020 May 2];cmaj.200685. Available from: https://www.cmaj.ca/content/cmaj/early/2020/05/01/cmaj.200685.full.pdf
  8. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research [Internet]. 2020 Apr 10 [cited 2020 Apr 15]; Available from: https://doi.org/10.1016/j.thromres.2020.04.013
  9. Coronavirus disease 2019 (COVID-19) • LITFL [Internet]. Life in the Fast Lane • LITFL • Medical Blog. 2020 [cited 2020 Apr 15]. Available from: https://litfl.com/coronavirus-disease-2019-covid-19/

Disclaimer

The above is intended to serve as a rapidly-created, accessible source of information curated by medical students and healthcare professionals. It is for educational purposes only and is not a complete reference resource. It is not professional medical advice, and is not a substitute for the discretion, judgment, and duties of healthcare professionals. You are solely responsible for evaluating the information above.