Introduction
COVID-19 (coronavirus disease 2019) is primarily a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. However, it may affect other organ systems like gastrointestinal, neurological, cardiac, hepatic, and renal systems. The complications include activation of blood clotting pathways due to viremia, superinfection, and organ dysfunction. Complications associated with blood clotting have also been reported in cases of coronavirus-infected and recovered people.
What Is D-Dimer?
D-Dimers are fibrin degradation products found in people with thrombotic disorders (disorders in which blood clots are formed within the blood vessels). It is used as a biomarker. If the value of D-Dimer in the blood is less than 0.5 microgram per milliliter, it is considered normal. The level of D-Dimer increases with age and pregnancy. Severe community-acquired pneumonia cases have shown an increased level of D-Dimer. After the coronavirus outbreak, studies revealed an elevated level of D-Dimer in infected and recovered patients. It can be used as a potential indicator to determine the prognosis in COVID-19 patients. Several studies show that evaluating the levels of D-Dimer in COVID-19 patients at the time of hospital admission has helped predict the severity of the case. Accurate and easily available biomarkers are useful in the medical intervention and management of COVID-19. Several studies have assessed the levels of D-Dimer in COVID patients to determine its significance as an indicator of prognosis and mortality. However, further studies are needed to ascertain a specific cut-off value of the D-Dimer for predicting the incidence of mortality in COVID-19 patients.
How Is D-Dimer Formed?
The blood clotting and its breakdown will produce a by-product called D-Dimer. Analysis of blood samples will help determine the level of D-Dimer in blood. It is released when the blood clot starts breaking down. The degradation of the fibrin will produce several substances.
Whenever there is an injury, blood clot formation will be initiated. In the blood, platelets are connected to a D subunit. Several platelets joined by the D subunits come together to form D-Dimers (joined through the D subunits), and along with fibrin and other factors, they form a clot. Soon after the clot has formed, the body's healing mechanism comes into action. It breaks down the clots to separate the D-Dimers (two D subunits linked together) from the platelets. The sensitivity and specificity of D-Dimers vary significantly based on the disease and the type of population assayed.
What Are the Indications for D-Dimer Testing?
D-Dimer test is of clinical importance in diseases like.
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Deep Vein Thrombosis: The formation of blood clots in the body's deep veins, like the legs.
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Pulmonary Embolism: Formation of blood clots in the pulmonary blood vessels.
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Disseminated Intravascular Coagulation: Small blood clots are formed throughout the body, blocking the small blood vessels and resulting in excessive bleeding due to the depletion of platelets and clotting factors.
- Studies after the coronavirus outbreak revealed an elevated D-Dimer level in the COVID-infected and recovered patients.
What Is the Significance of D-Dimer in COVID-19 Patients?
- Despite the fact that the coronavirus outbreak is a recent pandemic, extensive studies have been performed with limited resources to determine a better prognostic and treatment modality for the disease.
- Though it is primarily a respiratory disease, several cases have been reported with complications of the blood clotting mechanism. The levels of D-Dimers are increased in COVID-19-infected and recovered patients.
- Before the outbreak of the coronavirus pandemic, the D-Dimer was not identified as an important biomarker for viral and bacterial infections causing pneumonia. However, since the COVID-19 outbreak, elevated levels of D-Dimer and several blood clotting complications have been reported in the patients suggesting an important role in the disease. One of the studies from March to December 2020 in Nepal has shown that patients who were admitted to the hospital with high levels of D-Dimer in their blood were associated with significant levels of in-hospital fatality.
- Several studies revealed that in almost half of the reported COVID cases, the D-Dimer value was more than 0.5 micrograms per milliliters of blood. Some studies in China suggested that a D-Dimer value of greater than two micrograms per milliliters of blood was associated with an increased risk of in-hospital mortality. A similar study in India suggested a cut-off value of 1.4 micrograms per milliliter had a mortality risk. A systematic analysis of several studies found that a specific cut-off could not be fixed for the D-Dimer value to predict mortality risk. However, for ease of understanding and implementation of better treatment strategies, D-Dimer values greater than 1.5 micrograms per milliliter are considered a marker for mortality in COVID patients.
- The D-Dimer test is an inexpensive, widely available, and easy-to-perform test. It has a satisfying accuracy in determining the risk of in-hospital fatality in coronavirus-infected patients. It can be used as an important biomarker for identifying high-risk cases and implementing an appropriate medical intervention. Incorporating the D-Dimer test in the customary investigation and risk assessment of COVID patients can help overcome the global health challenge.
How Is D-Dimer Elevated in COVID-19 Patients?
The most common explanation in the literature for the elevated levels of D-Dimer in the blood is as follows.
- Viremia (existence of the virus in the blood).
- Cytokine storm syndrome (hyperactivation of the immune mechanism in response to the pathogenic virus will uncontrollably release pro-inflammatory cytokines like interleukin-2, interleukin-6, interleukin-8, interleukin-17, and tissue necrosis factor-alpha. The process will trigger the clotting pathways resulting in blood clot formation followed by its breakdown).
- Hypoxia (insufficient oxygen at the tissue levels) will trigger a pathway that predisposes blood clot formation.
- Coronavirus infection in the presence of comorbidities like hypertension, cardiovascular diseases, and diabetes mellitus makes the patient more prone to thrombosis resulting in elevated levels of D-Dimer.
Conclusion
From the above review, it is clear that the D-Dimer value at the time of hospital admission is an important biomarker to predict mortality risk. A value greater than 1.5 micrograms per milliliter is considered a high mortality risk in COVID-19 patients. The relative ease and availability of the test make it a suitable choice.
