A D-dimer test measures a protein fragment released into the bloodstream when a blood clot dissolves. This fragment is a product of fibrinolysis, the body’s natural process for breaking down the fibrin mesh that forms a stable clot. Its presence indicates two simultaneous biological processes: active clot formation and active clot breakdown. When an infection triggers a widespread inflammatory response, it activates the coagulation system. The resulting increase in clot formation and subsequent dissolution significantly raises the D-dimer concentration in the blood, reflecting the severity of systemic inflammation and the activation of the clotting cascade.
Understanding the D-dimer Test
The primary use of the D-dimer test is to help exclude venous thromboembolism (VTE), including deep vein thrombosis (DVT) or pulmonary embolism (PE). Because the test is highly sensitive, a negative result in a low-risk patient effectively rules out a major clot. D-dimer is generated when plasmin, the enzyme responsible for clot breakdown, acts upon cross-linked fibrin polymers. The amount circulating reflects the overall activity of the fibrinolytic system.
However, D-dimer elevation is not exclusive to VTE, meaning the test has low specificity. A wide variety of conditions other than a blood clot can cause levels to rise, such as recent surgery, trauma, internal bleeding, advancing age, liver disease, and pregnancy. Any systemic inflammatory state, including infection, is sufficient to trigger the coagulation cascade and increase D-dimer.
The Biological Link Between Infection and Clotting
Infection initiates a complex biological interaction between the immune system and the hemostatic system, often termed immunothrombosis. When pathogens invade, the body mounts a Systemic Inflammatory Response Syndrome (SIRS), releasing inflammatory signaling molecules that bridge the immune response to the coagulation cascade. The invading microbes or their toxins damage the endothelium, the inner lining of blood vessels. This endothelial injury exposes underlying tissue factors that powerfully activate the coagulation cascade.
The simultaneous activation of inflammation and coagulation creates a state where the body forms widespread, minute clots within the microvasculature. This extensive clotting attempts to wall off and contain the infection by trapping pathogens within the fibrin mesh. As the fibrinolytic system attempts to clear these micro-clots, the plasmin enzyme breaks down the cross-linked fibrin. The resulting release of D-dimer fragments into the systemic circulation causes the elevated test result seen during a severe infection.
Specific Infectious Diseases That Cause Elevation
The severity of the infection, rather than the specific type of pathogen, is the primary driver of D-dimer elevation. However, certain infectious diseases provoke a profound systemic inflammatory and pro-coagulant response.
Bacterial Infections
Severe bacterial infections leading to sepsis are a major cause of D-dimer elevation. Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response, reliably causes a marked increase in D-dimer. Examples include severe community-acquired pneumonia, complicated urinary tract infections, and abdominal infections. Invasive bacterial diseases, such as meningococcal infections, are associated with extremely high D-dimer levels, reflecting the overwhelming systemic insult.
Viral Infections
Viral infections are also prominent causes, especially those that trigger a strong inflammatory reaction. The SARS-CoV-2 virus (COVID-19) is a widely recognized example, where D-dimer elevation is a hallmark of severe disease. Other systemic viral illnesses like severe Influenza and Dengue fever can similarly activate the coagulation system. Even chronic viral infections, such as Human Immunodeficiency Virus (HIV), can lead to persistently elevated D-dimer levels due to ongoing, low-grade inflammation.
Interpreting D-dimer Results During Illness
When an elevated D-dimer is observed in a patient with a known infection, its interpretation shifts from a diagnostic tool for VTE to a marker of disease severity and prognosis. Extremely high D-dimer levels correlate directly with the degree of systemic inflammation and the risk of poor outcomes. Persistently high or rapidly rising levels suggest an increased risk of developing microvascular clotting, which can lead to organ dysfunction.
This may progress to Disseminated Intravascular Coagulation (DIC), a life-threatening condition characterized by widespread clotting and subsequent bleeding. Furthermore, elevated D-dimer in this context is associated with an increased risk of developing VTE, such as DVT or PE. For instance, in patients hospitalized with COVID-19, D-dimer levels greater than four times the upper limit of normal have been linked to a substantially higher risk of mortality.