D-dimer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

D-dimer is a fibrin degradation product. D-dimer levels are elevated in the plasma after the acute formation of a blood clot. The majority of patients with pulmonary embolism have some degree of endogenous fibrinolysis with an elevation in D-dimer levels, therefore there is a high negative predictive value in ruling out a pulmonary embolism when D-dimer levels are low. However a wide range of diseases are associated with mild degree of fibrinolysis which elevate D-dimer levels and contribute towards a reduced specificity and a poor positive predictive value of a high D-dimer level. This means that it is more likely that one can rule out a PE with a low D-dimer level, but cannot necessarily confirm the diagnosis of a PE based on a high D-dimer level. Other disease states that can also have a high d-dimer level include pneumonia, congestive heart failure (CHF), myocardial infarction (MI) and malignancy. False-negative values may occur in patients with prolonged symptoms of venous thromboembolism (≥14 days), patients on therapeutic heparin therapy, and patients with suspected deep venous thrombosis on oral anticoagulation, as these patients have will have low D-dimer levels in the presence of a PE.^[1][2]

The recurrence rate within the first few months following a first episode of VTE is not negligeable. In fact, it is estimated to be around 6% at 6 months following the first episode.^[3] Because of this, the duration of treatment with oral anticoagulation therapy must be long enough to decrease the risk of recurrence while not too long to cause bleeding complications. The duration of treatment of oral anticoagulation is most problematic in the category of patients suffering from their first episode of unprovoked VTE; therefore, a marker of risk of recurrence of VTE in this population in particular is needed to tailor the duration of their treatment.

An association between changes in D-dimer levels during and following discontinuation of oral anticoagulation was suggested more than a decade ago,^[4] and the prognostic role of D-dimer in predicting the rate of recurrence of VTE has been extensively studied.^[5] Studies have been consistent in their findings of an association between elevated D-dimer levels and higher rates of recurrence of VTE; as such, they suggest a possible role for D-dimer in predicting recurrence of thromboembolism and tailoring the duration of treatment of oral anticoagulation following VTE.^[6] Resuming oral anticoagulation treatment (OAT) in subjects with abnormal D-dimer levels following the discontinuation of the OAT reduced their risk of VTE recurrence.^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

D-dimer testing was originally developed in the diagnosis of disseminated intravascular coagulation. In the 1990s, they turned out to be useful in diagnosing thromboembolic process.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

D-dimer is fibrin degradation product (FDP) resulting from the sequential break down of fibrin by the enzymes thrombin, factor VIII and plasmin.

Fibrin degradation products (FDPs) are formed whenever fibrin is broken down by enzymes. In fact, FDP are formed as a result of the sequential actions of the following three different enzymes: thrombin, factor VIII and plasmin. Determining FDPs is not considered useful, as this does not indicate whether the fibrin is part of a blood clot (or being generated as part of inflammation).

D-dimers are unique in that they are the breakdown products of a fibrin mesh that has been stabilized by Factor XIII. This factor crosslinks the E-element to two D-elements. This is the final step in the generation of a thrombus.

Plasmin is a fibrinolytic enzyme that organizes clots and breaks down the fibrin mesh. It cannot, however, break down the bonds between one E and two D units. The protein fragment thus left over is a D-dimer.^[1]

Shown below is an image summarizing the formation of D-dimers and other fibrin degradation products as a result of the sequential action of the three enzymes: thrombin, factor VIII and plasmin.

Three genetic variants, F3, F5, and FGA, were associated with D-dimer levels accoding to data based on 13 cohorts involving 21 052 healthy individuals from 13 European ancestry. The locations of the three genetic variants F3, F5, and FGA are 1p22 1q24 and 4q32 respectively.^[2]

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