Plasmin, fibrin degradation products and D-dimer
Breakdown · D-dimer Alpha-2-antiplasmin
Plasmin is the serine protease that digests fibrin — and, if it escapes into plasma, fibrinogen and factors V and VIII — into fragments X, Y, D and E. Only fibrin that factor XIIIa has cross-linked yields a D-dimer, so a raised D-dimer means a clot was actually formed and then lysed, rather than fibrinogen merely being degraded. Alpha-2-antiplasmin neutralises free plasmin almost instantly.
Traced from the start
- Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
- Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
- Subendothelial collagen and von Willebrand factor
- Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
- Factor XaFactor VaProthrombin (factor II)
- Thrombin (factor IIa)
- Plasminogen and tissue plasminogen activatorCross-linked fibrin clot
- Plasmin, fibrin degradation products and D-dimer
Detail
- Degrades
- Cross-linked fibrin into D-dimer and other fibrin degradation products; also fibrinogen and factors V and VIII
- Restrained by
- Alpha-2-antiplasmin, cross-linked into the clot by factor XIIIa; alpha-2-macroglobulin; PAI-1; and TAFI
- D-dimer value
- High negative predictive value — a normal D-dimer with a low or moderate Wells score excludes deep vein thrombosis or pulmonary embolism without imaging
- False positives
- Pregnancy, advancing age, sepsis, malignancy, recent surgery or trauma, and any inflammatory state; an age-adjusted cut-off (age in years times 10 microgram/L above age 50) improves specificity
When it goes wrong
Alpha-2-antiplasmin deficiency, or hyperfibrinolysis in liver failure, prostatic surgery and cardiopulmonary bypass
Delayed bleeding from wounds after an initially adequate clot has formed; responds to tranexamic acid
Raised D-dimer together with thrombocytopenia, prolonged PT and APTT and a falling fibrinogen
Disseminated intravascular coagulation rather than simple venous thromboembolism — the D-dimer alone cannot distinguish them
Practise this structure
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