Clinical Information

Activation of the coagulation system results in the formation of fibrin molecules, which aggregate and are cross linked by factor XIIIa to produce a fibrin clot. The activation of the fibrinolytic system results in the conversion of plasminogen into the active protease plasmin, which cleaves fibrinogen and fibrin into fragments D and E . Due to the cross-linkages between the D-domains in the fibrin clot, the action of plasmin releases fibrin degradation products with cross-linked D-domains. D-Dimer is a result of this breakdown process.

A fibrin clot is broken down into a variety of “FDPs”, fibrin degradation products. The most characteristic molecule is two “D” fragments cross linked together. Due to the cross linkages the breakdown products will consist of various forms of different cross-linkages of “D and E” fragments. Therefore, there is the possibility of a variety of dimeric forms, which are variously linked and extended by the “E” fragments. The mixture of these degradation molecules varies from patient to patient and depends on the underlying disease as well as the severity of the disease state.

Since the presence of D-Dimer indicates the presence of an on-going coagulation activation together with a reactive fibrinolysis process, D-Dimer is elevated in thromboembolic disease such as Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). D-Dimer is elevated in DVT and PE, but increased levels are reported in many other clinical conditions. An assay for the D-Dimer is therefore non-specific for DVT and PE, and can not be applied as a confirmatory diagnostic marker. The strength of using D-Dimer determination lies in its role for exclusion diagnosis.

Pre-test probability: It has been shown that a scoring method using a clinical assessment model to determine pretest probability of DVT and PE has been useful in the diagnostic approach. Patients are individually assessed using a score based on the presence or absence of certain signs/ symptoms. Once scored, the patient is categorized as at low, moderate or high likelihood of having DVT/PE.

Biochemical markers of thrombin generation or fibrinolytic activity have been evaluated as adjunct to radiological scanning in an attempt to reduce the need for serial testing and to improve diagnostic accuracy. Assays for D-Dimer have been shown great promise as useful tests to exclude the presence of DVT and/ or PE. However, the positive predictive value and specificity of D-Dimer assay is limited. Thus, the main value of D-Dimer assay and the use of simplified clinical scoring is to help exclude the diagnosis of VTE.