Expert response to a high proportion of blood clots in COVID-19 patients

Earlier this week, the BBC reported that one-third of COVID-19 patients developed dangerous blood clots. Current therapies focus primarily on antiviral and potentially anti-inflammatory therapies, but these address only the direct effects of the virus. If the virus is a flood, these processes control the flood but do not consider the damage caused. Drug therapies that address this thrombus formation, including the use of anticoagulants, in addition to drugs that treat overdrive of the immune system or virus neutralization, and thrombolytics, especially urgent to the right dose and the right patient. Need to work on. ..

Is the diagram of “1/3” thrombosis of COVID-19 patients realistic? Why is it so high?

It is quoted that the number of patients undergoing intensive care is 40%, and case series have been reported from multiple countries. Patients in the ward have a higher prevalence, even if they are not the same size as those receiving intensive care.

This excess Thrombosis An autopsy report confirmed more extensive thrombosis in the lungs and thrombosis in blood vessels in other organs.

Are blood clots different from what you see every day in the clinic?

Unlike the typical thrombus, which represents the embolism phenomenon, there is a widespread view that the pulmonary artery thrombosis in these patients probably represents new thrombus formation. In other words, the clot was formed by new deposits within the blood vessels, rather than clots formed in other parts of the body that had migrated. This may explain the late onset of shortness of breath. In some patients, a more typical rapid onset of shortness of breath secondary to rapid occlusion of the pulmonary vascular tree was seen.

I think the combination of both is common across the patient group. Smaller peripheral thrombi represent de novo thrombus formation. The larger arterial thrombus is probably embolic.

What is the treatment strategy for thrombosis?

It was hypothesized that thrombosis could be addressed by managing excess cytokines and immune activation. This is a misunderstanding. Experience with other thromboses, including arterial thrombosis and venous thrombosis, has shown that the thrombus does not disappear when the cause is addressed. The thrombus is cleared by a turnover process called fibrinolysis, which is specific to the coagulation process. This can also be facilitated by a topical drug called Blood clot Buster (tissue plasminogen activator or streptokinase)

In the setting of thrombosis secondary to mild inflammation that is inherited or acquired or secondary hypercoagulation, anticoagulation therapy is the focus of treatment. Primarily, they can deal with the consequences of the coagulation system, ie prevent the progression and recurrence of thrombosis.

There is also considerable debate about whether all patients should receive therapeutic anticoagulant therapy. On the other hand, there are concerns about the potential risk of bleeding. A randomized trial is in progress, but despite the reported prevalence, the trial does not require screening.

Great emphasis is placed on antiviral and anti-inflammatory strategies, but sadly, coagulation research struggles to be badged as “important”. Antiviral and potential anti-inflammatory strategies may control “flood”, a cytokine storm associated with viral infections, while “flood damage”, alveolar and blood flow fibrin, is another mechanism. Need to deal with.

What do scientists think is the mechanism that causes increased blood coagulation in COVID-19 patients?

A consistent finding is an increase in d-dimer, usually a 4-10 fold increase. Also, in highly sick patients there is a 100- to 150-fold increase. Increased D-dimer is associated with increased mortality and morbidity. The relationship with the severity of lung disease is unclear.

Several explanations have been given and the mechanisms responsible for excessive thrombosis or abnormal coagulation of COVID-19 are not completely understood.

There are three possible mechanisms.

1. Abnormal coagulation may be secondary to the cytokine storm. This seems to be the most common idea, but it is interesting to note that patients do not have a concomitant decrease in fibrinogen or platelets. Cytokine storm coagulation disorders typically tend to be accompanied by decreased fibrinogen, decreased platelets, and increased d-dimer.
2. The second possibility is damage to the endothelial cells due to their proximity to the alveolar epithelium, leading to the spread of the bystander effect, severe inflammation. This mechanism may explain the excess pulmonary arterial thrombosis seen in this patient group. Usually, in this situation, fibrinolytic inhibitors increase in the alveoli and leak into the circulatory system.
3. The third possibility is that there is a direct infection of the endothelial cells. There was a case report showing this possibility. ..

What about investigating pulmonary artery thrombosis?

CT pulmonary angiography shows thrombosis of the pulmonary vasculature down to the subsegmental level. These patients have difficulty breathing, resulting in motion artifacts and the presence of lung pathology, making it difficult to visualize small blood clots.

Screening is important when recognizing a new pulmonary thrombosis, as it is unlikely that patients will have conventional clinical symptoms.

At our facility, a review of the data shows that elevated d-dimers can predict the presence of pulmonary thrombosis.

Minimal patients with high d-dimers require CTPA at approximately 4 to 6 times the upper limit of normal, and anticoagulant therapy addresses the contribution of PAT.

What Other Treatments Are Possible For Coagulation?

Anticoagulants usually tend to manage clots, but thrombolytics can also dissolve clots. Thrombolysis in pulmonary embolism can be done as a systemic therapy by administering the drug via a peripheral vein or catheter.

There have been several case series of venous tissue plasminogen activator with transient improvement in oxygenation. Most studies have included patients admitted for long-term intensive care, and the lack of impact on clinical outcome may be associated with fibrosis. Some studies have investigated whether nebulized tissue plasminogen activator helps improve oxygenation through lysis of fibrin membranes in alveolar and small vessel thrombosis.