Fibrin degradation products

Fibrinolytics. Figure 2 Various fibrin structures for plasmin. Fibrinogen (Fg) is converted to fibrin (F) by thrombin (T), and thrombin can also convert factor XIII (XIII) to activated factor XIII (Xllla). The latter produces crosslinks between fibrins (FxxF) and also may crosslink fibrin with a2-plasmin inhibitor (FxxFxxPI). The efficiency of digestion of these plasmin substrates by plasmin, resulting in the soluble fibrin degradation products (FDP), is different. The amount of FDP formed in time is expressed in arbitrary units. 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

D7. Deitcher, S. R., and Eisenberg, P. R., Elevated concentrations of cross-linked fibrin degradation products in plasma. An early marker of gram-negative bacteremia. Chest 103, 1107-1112... 

D-Dimer) (Other cross linked fibrin degradation products)... 

Fig. 9. Steps in the formation of fibrinogen-fibrin degradation products. The approximate molecular masses of fibrinogen degradation products in kilodaltons (KDa) are indicated.

By far the most widely measured marker of hemostatic activation is D-dimer, which is a product formed by the action of plasmin on cross-linked fibrin (95). D-dimer levels in plasma are generally elevated in DIC. The consumption of platelets and coagulation proteins as a result of thrombin generation leads to the deposition of fibrin thrombi at multiple organ sites. This triggers fibrinolysis with an increase in the formation of fibrin degradation products, which can cause bleeding at multiple sites. Because DIC can have a variety of causes and may coexist with systemic fibrinolysis, such as in pulmonary embolism or deep vein thrombosis, the d-Dimer test is not specific for DIC (95). 

Elms M. J., Bunce I. H., Bundesen P. G., et al. Measurement of crosslinked fibrin degradation products. An immunoassay using monoclonal antibodies. Thromb Haemost 1983 50,591 -4. 

WeitzJI, Leslie B, Hudoba M, Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors, Circulation 1998 97 544-552. 

Plasmin. Generated by proteolytic cleavage of plasminogen, a plasma protein synthesised in the liver. Cleavage is catalysed by tissue plasmiuogeu activator (t-PA), which is synthesised and secreted by endothefium. Plasmin proteolytically cleaves fibrin into fibrin degradation products, which inhibits excessive fibrin formation. 

Widespread hemorrhagic brain infarcts and intracranial hemorrhages tend to cause an acute or subacute global encephalopathy rather than stroke-like episodes. The diagnosis is confirmed by a low platelet count, low plasma fibrinogen, and raised fibrin degradation products and D-dimer. 

Korschenhausen DA, Hampel HJ, Ackenheil M, Penning R, Muller N (1996) Fibrin degradation products in post mortem brain tissue of schizophrenics A possible marker for underlying inflammatory processes. Schizophr Res 19 103-109. 

Epoetin has been abused by athletes, increasing the risk of hypertension and disseminated intravascular coagulopathy (10). In athletes epoetin causes increased blood viscosity, which will further increase during dehydration, leading to risks of myocardial infarction, cerebrovascular accident, or encephalopathy (10). Epoetin induces accelerated fibrinolysis, and so epoetin doping can be detected by analysis of fibrin degradation products in urine (10). In addition, hypochromic macrocytes are increased (10). 

Bleeding at sites other than the primary site (oozing at a central hne insertion site, hemarthrosis, and epistaxis) has been reported during treatment with recombinant factor Vila in four patients (7). The authors suggested that local fibrinolysis may have contributed to or actually caused bleeding from central hne insertion sites. In three cases they found raised fibrin degradation products and in two cases a 15-35% fall in plasminogen activity. 

Thrombophlebitis is seen in np to 10% of patients, and this effect, as well as effects on coagnlation (prolongation of the prothrombin and thromboplastin times, increased fibrin degradation products, and thrombocjTopenia), may be cansed by degradation prodncts of hemin (2). There is evidence that slower infnsion rates rednce the risk of adverse effects (3). 

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