D – dimer is an indispensable tool in patients presenting with symptoms indicative of venous thromboembolism (VTE).
Normal D – dimer levels, when integrated with low or intermediate clinical pretest probability of VTE can essentially exclude diagnosis of VTE and avoid need for imaging evaluation.
d-dimer determination has high sensitivity, but limited specificity for VTE particularly in older patients.
VTE-d-diner testing for VTE becomes less specific with advancing age.
Cross-linked fibrin degradation product, which forms as a result of a breakdown of fibrin.
A specific antigen derived from the degradation of factor XIIIa cross-linked fibrin.
The D-Dimer antigen measured is derived from the degradation of fibrin formed by the combined action of thrombin, factor XIIIa, and plasmin.
It is the smallest of the fibrin degradation products.
It is routinely measured as a proxy marker of activation of fibrinolysis.
The reference concentration of D-dimer is < 250 ng/mL, or < 0.4 mcg/mL.
Fibrolysis is activated as thrombus is formed, so the D-dimer becomes clinically useful to identify patients in whom pathological intravascular thrombus might be accumulating.
First step of formation thrombin cleavage exposes a polymerization site on fibrinogen that promotes binding of another fibrinogen or a monomeric fibrin molecule-fibrin monomers then bind to one another in an overlapping manner to form 2 molecule thick protofibrils.
The second step in its formation factor XIIIa covalently cross links fibrin monomers via intermolecular isopeptide bonds formed between lysine and glutamine residues within the soluble protofibrils and the insoluble fibrin gel.
The last step in formation, plasmin formed on the fibrin surface by plasminogen activation cleaves substrate fibrin at specific sites.
A wide variety of fibrin degradation products include the terminal degradation products of cross linked fibrin containing D-dimer and fragment E complex.
The antigen remains undetectable until released from cross-linked fibrin by the action of plasmin.
Indicates the presence of intravascular clot that has undergone lysis.
Useful test to exclude the diagnosis of venous thromboembolism.
In patients with low clinical probability of pulmonary embolism, a negative result on D-dimer test can be used to withhold imaging and anticoagulation.
D-dimer Levels increase with age, leading to lowest specificity for DVT diagnosis in older patients.
High molecular weight fragments containing D-dimer are present in patients with DIC and other thrombotic disorders.
Assays measure an epitope on degradation products of factor XIIIa-cross linked fibrin.
Rules out 30% of patients with pulmonary embolism when used as a first-line test with a normal level and a low clinical suspicion of embolism.
Has a 2-3% rate of false negative in pulmonary embolism.
The D-dimer test is considered safe and misses less than 1.85-2% of patients with PE.
Levels increase with age.
Elevated levels in pregnancy make it a less useful test for pulmonary embolism during pregnancy.
A positive test result is not useful because elevated D-dimer level is found in 40-69% of patients which may be caused by infection or inflammation.
Elevated levels may be caused by disseminated intravascular coagulation, pulmonary embolism, advanced age, pregnancy, postoperative status, trauma, cancer, vasoocclusive crisis in sickle cell disease, myocardial infarction and inflammatory states.
A fibrin formation degradation product is essential for tumor angiogenesis and tumor growth.
Elevated in patients with solid malignancies including prostate, cervical colon and lung cancers.
Levels can be correlated with tumor markers Cancer 125 and CEA.
Levels correlate with the depth of cancer invasion and nodal involvement at the time of surgical resection.
Levels a predictor of overall survival in patients with metastatic colorectal cancer.
May have a role in gauging duration of the use anticoagulants in thromboembolic disease.
PROLONG study compared individuals with at least 3 months of treatment with vitamin K antagonists for unprovoked thromboembolic disease with continued anticoagulation or not based on d-dimer levels at one month after discontinuance of the oral anticoagulant.
PROLONG study revealed that a high recurrence rate of venous thromboembolism of 15% for patients with elevated d-dimer levels and not given further anticoagulation, while patients with high levels of d-dimer given continued anticoagulation has a combined risk of recurrent venothromboembolism and bleeding of 2.9%.
PROLONG study rate of recurrent thromboembolism for patients with normal d-dimer levels and no further anticoagulation was 6.2%.
In patients presenting with suspected DVT, the age adjusted D-dimer cut off safely excludes DVT: among patients with d-dimer level between 500 µg per liter and their age adjusted cut off, none develop venous thromboembolism at three months, resulting in a 7.4% decrease in the proportion of patients in whom the diagnosis could be excluded: D-diner interpretation can and should be tailored, at least by age to allow for more precision.