Blood Clotting Problems: A Serious Complication of COVID-19

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While severe pneumonia and acute respiratory distress syndrome (ARDS) are the most prominent features of severe COVID-19, the novel coronavirus can also affect many other organ systems and bodily functions. Doctors have now recognized that, in many cases, non-respiratory manifestations of COVID-19 often may be related to disorders of blood clotting that result from this infection.

What Is a Blood Clot?

A blood clot is blood that has coagulated or clotted. While clotting is crucial in some circumstances—healing a skin wound by forming a scab, for example—blood clots that occur within arteries or veins can be dangerous and even life-threatening if they block the flow of blood to essential organs, including the heart, lungs, and brain.

Disordered clotting with COVID-19 is now recognized as one of its most difficult and dangerous manifestations. Doctors and researchers are still determining the causes of the clotting problems seen with COVID-19, as well as how to detect them early, how to prevent them, and how to treat them.

What Causes Clotting Problems With COVID-19?

Blood clotting abnormalities are common in people with severe COVID-19 who are hospitalized. In the large majority of cases, these clotting disorders mean an increased tendency to form blood clots. More rarely, bleeding can occur.

The causes of clotting disorders associated with COVID-19 are still somewhat speculative, but at least three likely causes have been identified:

  1. People severely ill with COVID-19 can develop widespread inflammation throughout their bodies. This inflammation seems to especially affect the endothelial lining of the blood vessels. Inflammatory damage to the endothelial lining is known to be a potent trigger for blood clot formation.
  2. Critically-ill hospitalized patients are usually immobilized, and immobilization (whether from COVID-19 or from any other cause), leads to venous stasis, or blood pooling in the veins of the legs. This venous stasis is a key factor in causing deep vein thrombosis (DVT), a result of clotting.
  3. There is evidence that COVID-19 can produce a "hypercoagulable state." This is a condition characterized by an elevation in circulating coagulation factors—blood proteins that, when activated, trigger blood clot formation. High blood levels of coagulation factors can lead to excessive blood clot formation.

Many investigators have noticed that the clotting issues seen with COVID-19 closely resemble a blood clotting disorder known as disseminated intravascular coagulation (DIC). DIC is a life-threatening condition characterized by excessive blood clotting, excessive bleeding, or both. It is seen in people with cancer, inflammatory diseases, infections, severe tissue injuries, liver disease, and several other conditions. In DIC, several of the circulating coagulation factors are abnormally activated, leading to excessive clot formation in blood vessels throughout the body. Sometimes, this widespread clotting ends up consuming the circulating coagulation factors, which eventually leads to abnormal bleeding.

In at least some patients with COVID-19-related clotting problems, the clinical similarities to DIC are striking. However, at this time it is not clear whether the coagulation disorders seen with COVID-19 actually represent a form of DIC, or instead are a unique disorder. Nonetheless, experience with DIC has given doctors taking care of people with COVID-19 a useful way to conceptualize the clotting problems they may see, and hints as to how to approach treatment.

Syndromes Related to Clotting Problems

For the most part, clotting problems associated with COVID-19 are seen only in people who are sick enough to require hospitalization. When clotting problems occur, they can produce several clinical syndromes that can be quite difficult to treat, and that can have severe consequences. These include:

Deep Vein Thrombosis (DVT)

The formation of blood clots in veins (usually, the leg veins), can become a significant problem. Not only can the DVT itself cause great discomfort—often, swelling of the leg along with pain and skin discoloration—but a clot can also break off and travel to the lungs, where it produces an even more serious problem, like pulmonary embolism.

Any sick person confined to a hospital bed is at high risk for DVT. But people hospitalized with COVID-19 seem to be at especially high risk for this condition. In one study, 25% of patients admitted to the intensive care unit with COVID-19 were found to have DVT.

Pulmonary Embolism (PE)

A pulmonary embolism is a blood clot that breaks loose and travels to the lungs, where it lodges in a pulmonary artery and disrupts normal blood flow to the lungs. It can lead to severe breathing difficulties, chest pain, and hemoptysis (coughing up blood), and if the clot is large enough, it can cause cardiovascular collapse.

Because critically ill people with COVID-19 already are very likely to have severe lung problems, a PE of any substantial size can threaten their survival.

Various studies have reported that as many as 20% to 40% of patients admitted to an intensive care unit with COVID-19 may have a PE during their hospitalization. This is a substantially higher incidence of PE than is seen in non-COVID-19 patients who are similarly ill with ARDS.

Microvascular Clotting

Widespread microvascular thrombosis refers to clotting in small blood vessels. It is regarded as one cause (and perhaps a predominant cause) of the severe pulmonary disease seen in critically ill patients with COVID-19, and can lead to multi-organ failure.

Microvascular clotting in the lungs can produce symptoms that are different from more "typical" forms of ARDS. For instance, doctors have noticed that, compared to people with typical ARDS, people with COVID-19 may have subjectively less shortness of breath with very reduced blood oxygen levels, and may require lower ventilator pressures to fill their lungs. These differences potentially can be explained by microvascular clotting in the lungs.

Large Artery Occlusion

Relatively few reports are available describing the sudden occlusion, or blocking off, of large arteries associated with COVID-19. Until late April 2020, this condition was not a real clinical concern.

However, on April 28, the New England Journal of Medicine published a report describing five patients with severe COVID-19-related respiratory distress who suffered large strokes due to sudden occlusion of large cerebral arteries. All were under the age of 50 and previously healthy.

Around the same time, Broadway actor Nick Cordero, 41, developed vascular occlusion of a leg and subsequently required amputation.

These disturbing reports have alerted physicians to the possibility that blood clotting associated with COVID-19 may cause the sudden—and catastrophic—occlusion of large arteries, even in young, previously healthy people. At the moment this potentially catastrophic clotting event appears to be a rare, or at least uncommon, problem.

Skin Lesions

Like many viral infections, COVID-19 has been associated with several skin rashes. In the case of COVID-19, at least three types of skin lesions may be related to microvascular occlusion:

  • Livedo reticularis: A purplish, web-like, circular skin discoloration. In many cases, livedo reticularis is caused by a blockage of the penetrating arterioles that supply the skin tissue with blood.
  • Petechiae: Red or purple dot-like skin lesions. The microscopic examination of petechiae from patients with COVID-19 suggests they are due to blockages in tiny blood vessels.
  • "COVID toes": One or more of a person's toes becomes swollen and red, often without much pain. It is similar in appearance to pernio or frostnip (a milder form of frostbite). COVID toes are most often in people who are not particularly ill with COVID-19, and seem to resolve on their own in a week or two.

Bleeding

Very few reports have highlighted bleeding problems with COVID-19, and the bleeding problems that have been reported (mainly intracranial hemorrhage) have generally been associated with anticoagulation therapy. So, whether the bleeding episodes seen with COVID-19 are more likely related to the disease or to the treatment cannot yet be determined.

Diagnosis

Because blood clotting disorders are so frequent in people hospitalized with COVID-19, screening blood tests like those listed below are recommended for all patients when they are first admitted to the hospital, and usually are repeated on a daily basis. No such testing is recommended at this time for people with COVID-19 who are not sick enough to be hospitalized since the risk of clotting problems appears to be extremely low in these people.

Testing includes:

  • A complete blood count (including platelets)
  • Fibrinogen blood levels (fibrinogen is a coagulation protein)
  • PT and PTT test (tests that measure how long it takes blood to clot)
  • A D-dimer test (a test that assesses whether blood clots are actively being formed within the vascular system).

People hospitalized with COVID-19 often have low or elevated platelet levels, mildly prolonged PT or PTT, elevated fibrinogen levels, and elevated D-dimer levels. If any of these abnormalities are noted, a clotting disorder may be present.

If your doctor suspects DVT, they will usually perform compression ultrasonography to confirm the diagnosis. If they suspect PE, they will perform a CT scan with pulmonary angiography if possible. An arteriogram is generally required to confirm large artery occlusion.

Microvascular clotting is often suspected on clinical grounds, but no specific testing is readily available for diagnosis. While tissue biopsy might help to document this condition, performing this invasive kind of testing isn’t feasible in people critically ill with COVID-19.

Treating Clotting Problems With COVID-19

There is no treatment for blood clotting problems that is specific to COVID-19, and very little firm clinical evidence exists on when and how to use anticoagulation therapy and antithrombotic therapy optimally in this disease. Controlled studies are ongoing to attempt to determine the most worthwhile approach.

In the meantime, the International Society on Thrombosis and Haemostasis (ISTH), while acknowledging our incomplete state of knowledge, has issued general guidelines that doctors can follow:

  • Based on evidence and the very high incidence of significant DVT and PE, the ISTH recommends prophylactic low-dose anticoagulation drugs for every patient admitted to the hospital with COVID-19. Higher-dose prophylactic anticoagulation (or even full-dose anticoagulation) is recommended for critically ill patients admitted to the intensive care unit, especially if their D-dimer levels are greatly elevated.
  • Full-dose anticoagulation is recommended for patients with proven or presumptive DVT or PE.
  • The more powerful (and dangerous) "clot-busting" thrombolytic drugs are reserved for patients who have a massive PE, a DVT that threatens a limb, a stroke, an acute heart attack, or a large artery occlusion that threatens a vital limb or organ.

Most doctors will continue with anticoagulation therapy for a month or two after a person with COVID-19 is discharged from the hospital.

A Word From Verywell

All hospitalized patients with COVID-19 should be closely monitored for signs of clotting disorders, and most should receive prophylactic anticoagulation. Acute clinical syndromes caused by blood clotting problems should be treated aggressively.

Fortunately, the large majority of people with COVID-19 become only mildly or moderately ill, and blood clotting problems appear to be very rare in these individuals.

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