D-Dimer Formation in the Body
Biochemical Formation Process
D-dimer is generated through plasmin-mediated proteolysis of crosslinked fibrin during fibrinolysis, representing the smallest fragment that is only produced when crosslinked fibrin is digested. 1
The formation occurs through a sequential process:
Initial coagulation activation: When blood clots form, fibrinogen is converted to fibrin monomers, which polymerize to create fibrin strands 1
Crosslinking: Factor XIIIa (activated Factor XIII) covalently crosslinks adjacent fibrin monomers at their D-domains, creating a stable fibrin mesh 1
Fibrinolysis: Plasmin cleaves the crosslinked fibrin, releasing various fibrin degradation products (FDPs) 1
D-dimer generation: D-dimer specifically refers to the covalently bound D-domains of adjacent fibrin monomers along with an E-domain of the opposite and staggered strand 1
Critical Distinction from Other Degradation Products
D-dimer is unique because it is only generated when crosslinked fibrin is digested, not from fibrinogen or non-crosslinked fibrin. 1 This specificity makes D-dimer more accurately represent both coagulation (generation of fibrin clots) and fibrinolysis (degradation of fibrin clots) compared to other fibrin degradation products 1.
Physiological Characteristics
Half-life: D-dimer has a relatively long half-life of approximately 16 hours in circulating plasma 1
Clinical implication: The long half-life obfuscates accurate interpretation of single time-point measurements, requiring sequential measurements to confirm active fibrinolysis 1
Molecular Specificity
The D-dimer molecule results from systematic degradation of vascular thrombi through the fibrinolytic mechanism 2. Monoclonal antibodies used in D-dimer assays are specific for epitopes on D-D fragments and are absent on fibrinogen and non-crosslinked fibrin fragments 1, ensuring the test specifically detects crosslinked fibrin breakdown rather than simple fibrinogen degradation 3.
Common Pitfalls in Understanding D-Dimer Formation
Not all fibrin degradation products are D-dimers: FDPs can be generated from plasmin-mediated proteolysis of both fibrinogen and fibrin, but D-dimer specifically requires crosslinked fibrin 1
Interference from other proteases: Fragments released from proteolysis of fibrinogen and fibrin by elastase and other enzymes in circulation (especially during sepsis or inflammation) can interfere with D-dimer testing but are not true D-dimers 1
Delayed detection: Because D-dimer formation requires both clot formation AND subsequent fibrinolysis, it is an indirect marker of hemostatic system activation rather than a direct measure of active clotting 4