Top, Clotting is always initiated by tissue factor activation of factor VII (FVII) in the extrinsic pathway. The tissue factor is present on the subendothelial surface of the blood vessel wall and on the surface of activated circulating monocytes. Once activated, FVII activates FIX of the intrinsic pathway (not shown) and FX of the common pathway. FX, once activated, activates prothrombin, leading to generation of thrombin, and thrombin, in turn, cleaves fibrinogen to form fibrin. Bottom, In disseminated intravascular coagulation (DIC), there is excessive activation of the extrinsic pathway. This leads to to increased fibrin formation and depletion of substrates, including (but not limited to) prothrombin and fibrinogen.
Fibrinogen is cleaved by thrombin to generate fibrin. Fibrin is then crosslinked by FXIII, resulting in an insoluble gel. Crosslinked fibrin is degraded by plasmin. This process, termed fibrinolysis yields soluble fibrin degradation products (FDPs). Fibrinogen may also be cleaved by plasmid to generate FDPs (fibrinogenolysis). Fibrin- and fibrinogen-derived FDPs are identical with the exception of D-dimer, which requires the action of plasmin on crosslinked fibrin.
A more granular look at the formation of FDPs and D-dimers from fibrinogen and fibrin. Fibrinogen is a dumbbell shaped molecule with 2 D domains flanking a single E domain. The sequential action of thrombin and FXIII results in the formation of crosslinked fibrin, with the crosslinks occurring between D domains on the longitudinal axis. Plasmin degrades fibrinogen and fibrin into fibrin degradation products (FDPs). Note that the D-dimer is unique to the breakdown of crosslinked fibrin. Other FDPs, namely D and E fragments are generated from plasmin-mediated degradation of both fibrinogen and fibrin. FDP assays detect all FDP fragments (from fibrinogen and fibrin breakdown), whereas the D-dimer assay measures D-dimers alone (from fibrin breakdown).
The ISTH scoring system is simple! It consists of just 4 parameters based on widely available, routine coagulation tests.
Parameter
Score
Comment
Fibrinogen (g/L)
>1 (0) <1 (1)
Overall sensitivity of low fibrinogen level reported to be about 30%.
Prothrombin time (PT) (seconds)
<3 (0) 3-6 (+1) >6 (+2)
Elevated in 50%-60% of patients with DIC at some point during course of illness.
Platelet count(109/L)
>100 (0) 50-100 (+1) <50 (+2)
Thrombocytopenia reported to occur in up to 98% of DIC cases.
D-dimers or FDPs
No increase (0) Moderate increase (+2) Severe increase (+3)
Elevated FDPs and D-dimers are sensitive, but not specific for DIC.
