The blood clotting process in normal individuals involves many intricate, complex steps including, in the final stages, the conversion of fibrinogen to fibrin monomer and subsequent polymerization to fibrin polymeric gel via the enzyme thrombin. It is generally accepted that prior to the formation of the clot, fibrin monomer combines with circulating fibrinogen to from soluble complexes. When the circulating fibrinogen concentration is insufficient to complex with the fibrin and therefore is insufficient to maintain the solubility of the fibrin monomer, the fibrin polymerizes and the clot is formed.
Ordinarily, in normal, healthy individuals there is no thrombin circulating in the blood, although there is some evidence to indicate that very small amounts of thrombin might from time to time be generated. Such amounts are usually insufficient to cause any significant intravascular coagulation. If some thrombin does happen to get generated as is normal in tissue injury at a wound for example, clots result from the action of the released thrombin. These clots are removed by the normal action of the body whereby plasmin dissolves the clot leaving small amounts of fibrin degradation products circulating in the bloodstream. Even if thrombin is present, it is likely that not all of the of the fibrin formed is converted to a clot in which case some free fibrin monomer is left circulating in the blood. So it can be seen that in normal individuals one would not be surprised to see some low level of fibrin monomer and fibrin degradation product circulating in the blood.
If, however, for some reason the coagulation system becomes abnormal in a way which results in larger amounts of thrombin than is normally encountered, then significant intravascular coagulation can occur. The coagulation process is of course accompanied by corresponding high concentrations of the soluble complexes of fibrin monomer and fibrinogen as indicated previously. The body attempts to remove the fibrin monomer - fibrinogen complex via the plasmin route as fast as it is being formed via the thrombin route. When thrombin levels are too high however, the thrombin mediated reaction overwhelms the plasmin reaction leaving fibrin monomer clearly discernible in the blood. Therefore, the concentration of fibrin monomer present is a measure of how abnormally high the thrombin level is and therefore and indication of the tendency of the patient toward intravascular coagulation. Since direct measurements of thrombin are not usually possible (the enzyme is rapidly removed by circulating inhibitors) it is very desirable to measure the fibrin monomers formed.
Unfortunately, the detection of fibrin monomers has not been readily achieved in the prior art due, at lease in part, to the fact that attempts to precipitate low levels of monomers with protamine sulfate have also caused the precipitation of fibrinogen. Fibrinogen precipitates as a white flocculent material easily distinguishable from the gel or strands formed from fibrin monomers. It is difficult at low concentrations to clearly identify the fibrin gel in the presence of the flocculent fibrinogen precipitate, however.
In view of this, the early detection of intravascular coagulation is somewhat uncertain when presently available test methods are relied upon. Since effective use of therapy depends, to a large extent, on its initiation in the early stages prior to irreversible damage, early diagnosis of low levels of intravascular coagulation is critical.