It is recognised that the SARS-CoV-2 virus causes clinical symptoms of various degrees, ranging from normal flu-like symptoms to death, particularly in elderly and comorbid patients. New research has also found that the young and healthy are more vulnerable to the infection. The multifaceted aspect of its presentation at different stages is a significant factor adding to the complexity of treating COVID-19. COVID-19-associated coagulopathy resulting in thrombosis, multi-organ injury, and death is one such manifestation/complication. A good understanding of the causes of COVID-19-associated coagulopathy is thus crucial. Current information and recommendations on the use of anticoagulation therapy in affected patients are discussed here.

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Pathogenesis of intravascular coagulation in COVID-19

One of the main problems associated with COVID19 is the risk for intravascular coagulopathy causing death. In autopsied cadavers, direct detection of microvascular thrombosis in COVID-19 patients has been described. The reported features of COVID-19-associated coagulopathy usually involve increased d-dimer, fibrinogen, and platelet counts which result in a prothrombotic condition that promotes thromboembolic events noted in critically ill patients regardless of pharmacological thromboprophylaxis.

While the underlying mechanisms of coagulopathy associated with COVID-19 has not been completely clarified, the current line of thought entails endothelial dysfunction as essential. Infection with SARS-CoV-2 has been shown to cause a proinflammatory environment contributing to the release of proinflammatory molecules including cytokines such as IL-6, IL-1β, IL-2, IL-4, tumor necrosis factor alpha (TNF-a), interferon gamma (IFN-γ), granulocyte colony stimulating factor, as well as C-reactive protein (CRP) and d-dimer.

The alterations in inflammatory parameters further promote a pro-inflammatory state with numerous proinflammatory cells in the circulatory system perpetuating endothelial damage and platelet activation leading to aberrant activation of coagulation (Fig. 1). Also, this proinflammatory hyperproteinemic state induced by SARS-CoV-2 may lead to a COVID-19-associated hyperviscous state thought to be an important link between inflammation and coagulopathy in critically ill COVID-19 patients.

Recommendations 

Present general recommendations for treating coagulopathy in COVID-19 patients have been drafted by prominent societies in the field including the American College of Cardiology, the American Society of Hematology, and the International Society of Thrombosis and Haemostasis.

In the absence of active bleeding or except when the platelet count is <25 x 10⁹/L or the fibrinogen amount is <0.5 g/L, the prophylactic LMWH dosage is prescribed for all hospitalised COVID-19 patients as per the latest guidelines. As per these recommendations, pharmacological thromboprophylaxis is not contraindicated in people with abnormal PT or aPTT. Where pharmacological thromboprophylaxis is contraindicated, mechanical thromboprophylaxis should still be employed.

These recommendations are focused on evidence that severely raised D‐dimer levels are associated with substantial mortality in COVID‐19 patients, and that multiorgan failure is more likely in those who are susceptible to coagulopathy; thus, inhibiting thrombin generation can help prevent death in patients.

In addition, LMWH is considered to have anti-inflammatory properties that may offer additional utility to patients with COVID who have marked pro-inflammatory cytokine elevation.

The existing recommendations approved by these societies are universal, allowing scope for improvements to address the needs of individual organisations. Specifics of how often and at what times D-dimers can be calculated are specific to the institution. However, as patients report to the emergency room or outpatient clinic, having a baseline d-dimer level is deemed acceptable and studies have demonstrated that a cut off value of >1 μg/mL will categorise patients at higher risk of poor outcomes.

The reader is guided to the websites of various institutions such as Brigham and Women's Hospital, Massachusetts General Hospital, and the University of Washington for institution-specific guidance to view the most up-to-date standards and policies.

To summarise, COVID-19 is a hypercoagulable condition that leads to increased mortality. A complex interplay of several pathways includes the pathways inducing aberrant coagulation in COVID-19. In order to thoroughly elucidate these mechanisms, evaluate appropriate doses of anticoagulation treatments, and research on other therapeutic modalities and clinical studies are underway. In the meantime, organisations such as ASH and ISTH have formulated universal recommendations for anticoagulation, with variations encouraged to satisfy the needs of individual organisations.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Monish S Raut is a Consultant in Cardiothoracic Vascular Anaesthesiology. His area of expertise is perioperative management and echocardiography with numerous publications in various national and international indexed journals.