From the Guidelines
D-Dimer is a fibrin degradation product that forms when cross-linked fibrin is broken down by plasmin during fibrinolysis, and its elevation indicates active thrombosis and clot breakdown, making it a useful screening test for conditions like deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation, as supported by the most recent study 1. The pathophysiology behind D-Dimer involves the coagulation cascade and subsequent fibrinolysis. When tissue injury occurs, the coagulation cascade is activated, leading to the conversion of fibrinogen to fibrin by thrombin. Fibrin monomers are then cross-linked by factor XIII to form a stable clot. As the body begins to heal, the fibrinolytic system activates plasminogen to plasmin, which breaks down the cross-linked fibrin into various fragments, including D-Dimer. Some key points to consider about D-Dimer include:
- D-Dimer specifically contains two D domains from the original fibrin molecule that remain connected by cross-links, as noted in 1.
- Elevated D-Dimer levels indicate that both coagulation and fibrinolysis have occurred, suggesting active thrombosis and clot breakdown, which is supported by 1 and 1.
- D-Dimer lacks specificity as it can be elevated in many conditions including pregnancy, inflammation, cancer, recent surgery, and advanced age, as mentioned in 1, 1, and 1.
- The normal range for D-Dimer is typically less than 500 ng/mL FEU (Fibrinogen Equivalent Units), though this may vary by laboratory and testing method, as noted in 1 and 1. It's also important to consider the limitations and potential issues with D-Dimer testing, such as:
- The need for accurate D-Dimer reporting, as emphasized in 1 and 1.
- The potential for false-positive results, particularly in patients with certain medical conditions or who are taking certain medications, as mentioned in 1 and 1.
- The importance of using age-adjusted cutoffs for D-Dimer levels, as recommended in 1 and 1.
From the Research
Pathophysiology of D-Dimer
- D-dimer is a soluble fibrin degradation product that results from the systematic degradation of vascular thrombi through the fibrinolytic mechanism 2.
- It is an indirect marker of fibrinolysis and fibrin turnover, exhibiting unique properties as a biological marker of hemostatic abnormalities as well as an indicator of intravascular thrombosis 2.
- D-dimer is the smallest fibrinolysis-specific degradation product found in the circulation, and its level is a marker of coagulation and fibrinolytic system activation 3.
Formation and Degradation
- D-dimer derives from degradation of cross-linked fibrin by plasmin 3.
- The origins of D-dimer are related to hemostasis, including platelet and vascular function, coagulation, fibrinolysis, and hemostasis 4.
Clinical Applications
- D-dimer has been extensively investigated for excluding the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication 2.
- It has also been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and for monitoring other conditions in which the patient is at high risk of bleeding or thrombosis 2.
- D-dimer levels can predict clinical severity of COVID-19, and escalated anticoagulation based on D-dimer levels can be associated with a lower risk of mortality in patients with severe COVID-19 3.
Limitations and Pitfalls
- D-dimer elevation can occur in a constellation of clinical scenarios, including age, pregnancy, and cancer 2.
- The assay lacks clinical standardization, and D-dimer levels can be above the threshold in several other conditions than thrombosis 3.
- Diagnostic errors can occur throughout the pre-analytical, analytical, and post-analytical phases of the testing process 5.