How we manage a high D-dimer

Abstract

D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), and to evaluate the risk of VTE recurrence, as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy, and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, ranging from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals with increased D-dimer without signs or symptoms of thrombus formation. This narrative review is dedicated to the management of these cases by the hematologist.

Figure 1.

Mechanism of D-dimer formation. (Top; coagulation process) Circulating human fibrinogen is made up of three pairs of polypeptide chains, designated Aα, Bb and g. Thrombin converts plasma fibrinogen to fibrin monomers by cleaving fibrinopeptides A and B. Polymerized fibrin monomers are stabilized by Factor XIII (activated by thrombin) into an insoluble cross-linked fibrin net. (Bottom; fibrinolytic process) Plasminogen is activated to plasmin, which releases soluble D-dimers and other fragments, including E fragments, from fibrin polymers. Finally, these soluble products are cleared from the bloodstream by the liver.

Figure 2.

Proposed algorithm for the diagnostic evaluation of venous thromboembolism. VTE: venous thromboembolism.

Figure 3.

Proposed algorithm for the management of cases with increased D-dimer levels. VTE: venous thromboembolism.