• In moderate to severe cases of Covid-19, the release of inflammatory mediators (namely: IL-1, IL-6, and TNF-alpha = Cytokines) inside the alveolar sacs are associated with what's known as 'the Cytokine Storm'.

  • As a response to such massive release of cytokines (cytokine storm), as a result, this will cause vascular vasodilation and an increase in the alveolar capillaries. Subsequently, alveolar damage and massive release of all inflammatory (cytokine) mediators into the bloodstream.

  • As a result, in severe Covid-19 cases, such massive levels of cytokine in the systemic circulation can lead to Systemic Inflammatory Response Syndrome (SIRS), which can potentially lead to Septic Shock.

  • Septic shock causes hypotension, which leads to a severe decrease in organ perfusion.

  • In the liver, such decrease in perfusion cis associated with an increase in transaminases, Acute Phase Reactant Protein (APRP) and increase in the hepatic fibrinogen production.

  • As a result of such multi-organ failure, and due to the continuous release of inflammatory mediators from different organs, this will lead to an increase in the d-Dimer in the blood and acute lymphopaenia, hence the combination of increased fibrinogen and d-Dimer will contribute toward coagulopathy and thrombosis

  • An international panel provides guidance on prognostic variables and management strategies for COVID-19–associated coagulopathy.

  • Based on that, patients with severe Covid-19 illness are also (in addition to acute respiratory failure) likely to have coagulopathy.

  • As such, experts from the International Society on Thrombosis and Haemostasis (ISTH) have created an interim guidance statement on the management of coagulopathy in COVID-19 patients. The key points include the following:

  1. Upon presentation of COVID-19, the measurements advised, in order of importance, are of d-dimer, prothrombin time, and platelet counts.

  2. Increased d-Dimers are commonly reported in patients with severe illness and may predict mortality.

  3. The d-Dimer is the most prognostically relevant of these variables; further, three- to fourfold increases in d-Dimer may signal the need for admission in patients without other clear indicators of severity. This will, of course, depend on hospital bed availability.

  4. Prolongation in prothrombin times and degree of thrombocytopenia (100–150×109/L) have been modest.

  5. In addition to the above parameters, fibrinogen should be monitored; non-survivors with severe illness have developed disseminated intravascular coagulation (DIC) around day 4; significant worsening in these parameters at days 10 and 14 was also reported.

  6. The ISTH panel advises the use of prophylactic dose low-molecular-weight heparin unless there is active bleeding or a platelet count of <25×109/L; it is hoped that this strategy will impact septic-like coagulopathy and protect against venous thromboembolism.

ISTH Disclaimer:

  • The panelists emphasize the interim nature of this statement, as management strategies will evolve as our knowledge base increases. Importantly, included laboratory tests are widely available, and monitoring of the d-Dimer, platelet count, prothrombin time, and fibrinogen is common in critically ill patients.

References:
[1] EMGuidance Clinical Pharmacologist - Dr. M Irhuma
[2] Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020 Mar 25
[3] Brady L. Stein, MD, MHS reviewing Thachil J et al. J Thromb Haemost 2020 Mar 25

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