Cross-linked fibrin clot

Fibrin and control · Fibrinogen (I) 2-4 g/L Thrombin time

Thrombin cleaves fibrinopeptides A and B from the alpha and beta chains of fibrinogen, allowing fibrin monomers to polymerise end-to-end and side-to-side into a soluble gel. Factor XIIIa then forms covalent bonds between adjacent D-domains, making the mesh mechanically strong and resistant to plasmin. Those cross-linked D-domains are the origin of the D-dimer.

Traced from the start

  1. Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
  2. Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
  3. Subendothelial collagen and von Willebrand factor
  4. Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
  5. Factor XaFactor VaProthrombin (factor II)
  6. Thrombin (factor IIa)
  7. Cross-linked fibrin clot

Detail

Substrate
Fibrinogen (factor I), normally about 2-4 g/L, a hepatically synthesised acute-phase reactant
Steps
Thrombin gives fibrin monomer, which polymerises spontaneously into a urea-soluble gel, which factor XIIIa then cross-links into an insoluble clot
Stabilised by
Factor XIIIa, which also cross-links alpha-2-antiplasmin into the fibrin so the clot resists its own lysis
Measured by
Clauss fibrinogen assay and thrombin time; viscoelastic testing (TEG, ROTEM) reports clot strength directly

When it goes wrong

Fibrinogen falling below about 1.5 g/L in major obstetric or trauma haemorrhage

Clot simply fails to form; fibrinogen is the first factor to reach a critical level in massive bleeding, so cryoprecipitate or fibrinogen concentrate is given early and guided by a Clauss level or viscoelastic testing

Dysfibrinogenaemia, inherited or acquired in hepatocellular carcinoma and chronic liver disease

Prolonged thrombin time and reptilase time with a normal or raised fibrinogen antigen but low functional activity; patients may bleed or thrombose

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