What is D-Dimer?
D-dimer is a specific degradation product formed when cross-linked fibrin is broken down by plasmin during fibrinolysis. Fibrin, a protein present in the blood, plays a crucial role in clot formation. In healthy individuals, low levels of D-dimer circulate in the blood. However, when there is active clot formation and breakdown within blood vessels, D-dimer levels increase. Elevated D-dimer is commonly associated with conditions such as myocardial infarction, stroke, pulmonary embolism, venous thrombosis, disseminated intravascular coagulation (DIC), surgery, tumors, infections, and tissue necrosis.
Conditions Leading to Elevated D-Dimer Levels
Beyond the well-known venous thromboembolism (VTE) conditions—including acute pulmonary embolism (APE), deep vein thrombosis (DVT), and cerebral venous sinus thrombosis (CVST)—D-dimer can also be elevated in non-thromboembolic diseases. These include acute aortic dissection (AAD), aneurysm rupture, stroke, DIC, sepsis, acute coronary syndrome (ACS), and chronic obstructive pulmonary disease (COPD). Additionally, factors such as advanced age, recent surgery or trauma, and thrombolytic therapy can elevate D-dimer levels.
Clinical Applications of D-Dimer Testing
1) D-Dimer and Venous Thromboembolism (VTE) and Anticoagulation Therapy
VTE encompasses deep vein thrombosis and pulmonary embolism. Classic pulmonary embolism symptoms include chest pain, hemoptysis, and shortness of breath, but the classic triad is uncommon. Diagnosis typically involves CT pulmonary angiography (CTPA), ventilation/perfusion (V/Q) scans, magnetic resonance pulmonary angiography (MRPA), and pulmonary angiography—the latter being the gold standard but less used due to invasiveness. Studies confirm markedly higher plasma D-dimer levels in DVT and PE patients compared to healthy individuals. D-dimer levels increase with age, necessitating age-adjusted thresholds: 500 μg/L for those under 50 years and 5000 μg/L for those over 50. Clinical scoring systems like Wells and Geneva scores further refine risk stratification and threshold use. Positive D-dimer results in VTE patients are associated with higher recurrence rates, particularly in males, and influence decisions on anticoagulant therapy duration.
2) D-Dimer and Disseminated Intravascular Coagulation (DIC)
DIC is a complex hemorrhagic condition triggered by various factors causing widespread clotting and bleeding. D-dimer levels rise significantly early in DIC and can increase ten- to hundred-fold as the disease progresses. D-dimer and fibrin degradation products are essential markers in the diagnosis of DIC per international guidelines.
3) D-Dimer and Cardiovascular Diseases
Elevated D-dimer levels are seen in atrial fibrillation, stroke, and cardiac arrest. Studies link higher D-dimer levels with increased risk of cardiovascular mortality and larger stroke volume. Follow-up studies in older males with atrial fibrillation show that elevated D-dimer predicts stroke occurrence. Moreover, D-dimer serves as a prognostic marker for poor outcomes and mortality post-cardiac arrest.
4) D-Dimer and Malignant Tumors
Cancer patients often exhibit elevated D-dimer due to tumor-related activation of coagulation and fibrinolytic systems, closely associated with tumor invasion and metastasis. Significant D-dimer elevation without typical symptoms should prompt consideration of underlying malignancy after excluding other causes. Prospective studies indicate combined D-dimer and high-sensitivity C-reactive protein testing can guide optimal anticoagulation duration in cancer-associated thrombosis.
5) D-Dimer and Pregnancy
Approximately 26.7% of pregnant women show mild D-dimer elevation, peaking in the third trimester and normalizing postpartum. Pregnancies complicated by hypertensive disorders, preeclampsia, or gestational diabetes exhibit significantly higher D-dimer levels. Elevated D-dimer correlates with severity in preeclampsia and can predict risks such as preterm delivery and prolonged pregnancy. It also shows correlation with in vitro fertilization failure rates.
6) D-Dimer and COVID-19
In COVID-19, early stages show normal or decreased white blood cell counts and lymphopenia. Some patients exhibit elevated liver enzymes, lactate dehydrogenase, muscle enzymes, and myoglobin. Critically ill patients often have elevated troponin and inflammatory markers. Elevated D-dimer and progressive lymphopenia are common in severe cases, reflecting hypercoagulability and inflammation.
7) D-Dimer in Type 2 Diabetes and Diabetic Nephropathy
Both conditions show significantly elevated D-dimer levels, with diabetic nephropathy patients exhibiting higher fibrinogen and D-dimer than those with diabetes alone. Disease progression directly affects these coagulation markers, making D-dimer a useful indicator for disease severity assessment.
8) D-Dimer and Mycoplasma Pneumonia (MPP)
Severe MPP often presents with elevated D-dimer levels, significantly higher in critical cases. Severe infections can cause local hypoxia, ischemia, and acidosis, damaging vascular endothelial cells and exposing collagen, which activates the coagulation system and creates a hypercoagulable state with microthrombi formation. Concurrent activation of fibrinolytic, kinin, and complement systems leads to increased D-dimer.
9) D-Dimer and Henoch-Schönlein Purpura (HSP)
Acute HSP involves hypercoagulable states and enhanced platelet function, causing vasospasm, platelet aggregation, and thrombosis. Elevated D-dimer typically appears two weeks after onset and varies by clinical stage, reflecting systemic vascular inflammation. Persistently high D-dimer predicts poor prognosis and renal involvement.
10) D-Dimer and Systemic Lupus Erythematosus (SLE)
SLE patients experience coagulation-fibrinolysis abnormalities, more pronounced during disease activity, increasing thrombosis risk. D-dimer levels are significantly higher during active phases compared to remission, serving as a marker of disease activity.
Interpretation of Positive D-Dimer Results
A positive D-dimer test indicates abnormally high levels of cross-linked fibrin degradation products in the body, signaling significant clot formation and breakdown. However, it does not specify the clot’s location or cause. Elevated D-dimer may result from VTE or DIC but can also arise from recent surgery, trauma, infection, liver disease, pregnancy, seizures, cardiac diseases, and certain cancers.
Limitations and Influencing Factors of D-Dimer Testing
While useful as an adjunctive test, D-dimer should not be the sole criterion for diagnosing diseases, particularly DVT and PE. Anticoagulation therapy can cause false negatives. Elevated D-dimer concentrations are common in the elderly and may yield false positives in patients with elevated rheumatoid factor. Other factors such as hypertriglyceridemia, lipemia, bilirubin, and improper sample collection or handling causing hemolysis may also produce false-positive results.
Conclusion
D-dimer is a valuable biomarker reflecting coagulation and fibrinolytic activity, aiding in diagnosing and managing various thrombotic and non-thrombotic conditions. Accurate interpretation requires consideration of clinical context, patient age, and potential confounding factors to optimize patient care and treatment outcomes.
