Blood clots in the lung may be a major cause of COVID-19 deaths

Many infected patients had elevated levels of a marker of thrombosis in blood vessels

Most needed: The critical need is for early recognition and intervention with blood thinners for COVID-19 patients.

The major fear of COVID-19 infection is the significant fatality associated with it. Even though death from this infection has been relatively low in India and is <1% in Tamil Nadu, given the very large number of people infected, significant numbers continue to die. Based on the data available so far, it is clear that the cause of death in almost all patients is respiratory failure. What is its cause? Unlike what would be expected in a viral infection in the lungs, it is not the pneumonia itself, like in most previous influenza outbreaks, but rather surprisingly it is early and progressive clotting of blood in the lungs (pulmonary thrombosis) which impairs blood supply and gas exchange leading to respiratory failure. This mechanism is supported by several levels of evidence.

First, it has been recognised from the very early reports that very high proportions of patients with COVID-19 infection presenting to hospitals had elevated levels of d-dimer, a general marker of thrombosis in blood vessels.

Those with highly elevated d-dimer levels were more prone to severe respiratory complications and death. In most of these patients, there are no other sites of thrombosis to explain the raised d-dimer such as the leg veins which is much more common but has only been reported in a few patients late in their illness after they have been in the hospital for several days.

Strongest evidence

Second, the strongest evidence for this extensive microvascular thrombosis comes from several autopsy studies from different countries. All these have shown extensive blood clots in the small vessels of the lung (microvascular thrombosis - MVT) with only modest evidence of the pneumonia suggesting that it is the blood clots which cause poor oxygenation and respiratory failure.

Endothelial cells

Third, it is also known now that the receptors on the cells in the air-pockets of the lung which allow entry to the COVID-19 virus into those cells, are shared by the endothelial cells which line the blood vessels of the lung. Autopsy studies have confirmed distinct infection in these cells which then trigger blood clotting in the small blood vessels. If not controlled immediately, this rapidly extends and leads to treatment unresponsive respiratory failure.

Fourth, the manifestation of ‘silent pneumonia’ or ‘silent hypoxia’ that is being increasingly recognised even in the lay media where relatively well-looking people have low blood oxygen and then suddenly collapse, most likely due to extending pulmonary thrombosis.

Other mechanisms of lung damage could also cause death in a few patients but formation of blood clots in the lung is the most consistent problem in nearly all cases.

Need for interventions

The critical need therefore is for early recognition and intervention with blood thinners (anti-coagulation) in this illness and with appropriate doses. This can be easily implemented in all hospitals based on some simple assessments:

Rate of breathing at rest (say above ~20/minute) and lowered level of oxygen in the finger (pulse-oximeter, which is easily checked in hospitals at presentation - less than 93%) even when they look relatively well. If possible, d-dimer levels should be checked immediately. If found to be elevated (more than 2-3 fold above normal), this would indicate the evolving condition in the lung. Such patients should immediately receive commonly used blood thinners such as heparin or low molecular weight heparin (LMWH) in therapeutic doses till the symptoms resolve. In those with higher risks of complications, preventive doses of LMWH have been advised soon after diagnosis. These medicines may be contraindicated in certain situations. So proper medical supervision is necessary. Careful monitoring for adverse effects must also be done.

It is important therefore that the public as well as health care professionals be aware of this problem of blood clots in the lung whose severity is unique to COVID -9. There is of course need for more studies to determine the right doses at the right stages of the disease. While such must be considered, they will never include all the patients infected but who must all receive blood thinners as indicated. This strategy has been shown to be effective and will reduce the mortality due to COVID-19 infections in India even further.

(The writer is a professor of medicine at the Christian Medical College, Vellore)