New methods in coagulation.

Abstract

Recent advances in the elucidation of the molecular biochemistry of the coagulation proteins have provided the foundation for the development of synthetic substrates. These substrates are oligopeptide with either a chromophore or fluorophore group attached to the C-terminal end. They may be used in the laboratory to assay for a number of the serine proteases involved in either coagulation or fibrinolysis. Also, by suitably modifying the assay system, the various inhibitors can be quantitated. These substrates promise to revolutionize the coagulation laboratory allowing for more precise quantitation of trace enzymes and also improved standardization and precision of coagulation assays. In addition to these substrates, the introduction of a number of immunologic procedures into the diagnostic laboratory have been of major importance in elucidating the heterogeneity of hereditary coagulation defects. By correlating the immunologic assays, coagulation assays and clinical picture, a number of subgroups of hereditary deficiencies have been identified. Also, the immunologic assays have provided a means for identifying the carrier state of hemophilia A and have significantly contributed to the improved diagnosis of von Willebrand's disease. The use of ristocetin cofactor assays, when used in conjunction with the Factor VIII antigens, have enable the laboratory to more accurately diagnose the majority of patients with von Willebrand's disease. Ristocetin cofactor may be assayed utilizing either formalin fixed or washed platelets and recently a snake venom has been introduced to assay for this particular aspect of the Factor VIII complex. Platelet specific proteins (i.e., platelet factor 4 and beta-thromboglobulin) may be assayed utilizing either radioimmunoassays or in the case of platelet factor 4 modified coagulation assays. These proteins provide evidence of in vivo platelet activation and hopefully may, in the future, be correlated with platelet kinetics.