MOLECULAR MARKERS OF HEMOSTATIC ACTIVATION - APPLICATIONS IN THE DIAGNOSIS OF THROMBOSIS AND VASCULAR AND THROMBOTIC DISORDERS

The recognition of molecular marker events leading to hemostatic and t hrombotic disorders and technologic advances in molecular biology and immunology has added a new dimension in the diagnosis of bleeding and thrombotic disorders. Pathophysiologic activation of coagulation, fibr inolysis, kallikrein-kinin system, vascular stress, and intercellular interactions result in the generation of cell/process specific markers of a pathophysiologic event. It has been two decades since the concep t of molecular markers was first introduced in the diagnosis of hemost atic and thrombotic disorders. However, due to cost/technologic limita tions and lack of understanding of this field at various levels its us age in clinical laboratory diagnosis was rather limited. With the adve nt of such analytical techniques such as enzyme-linked immunosorbent a ssays (ELISA) a disease specific molecular profiling can be readily ac complished. Subclinical activation of platelets, endothelial distress, and aberrations of the protease network can be readily diagnosed by u tilizing specific assays. The concept of hypercoagulable state is now validated utilizing such markers of hemostatic activation such as plat elet factor 4, thromboxane B-2, fibrinopeptide A and plasminogen activ ator inhibitor. Cardiovascular disease risk and blood vascular disorde rs can be diagnosed utilizing these markers. The monitoring of antithr ombotic drugs that do not produce any anticoagulant effects on blood c an also be readily accomplished by using some of these analytes. Using specific monoclonal antibodies, various diagnostic profiles for such disorders as thrombotic stroke, disseminated intravascular coagulation , primary fibrinolysis, hemodynamic disorders, and diseases of vascula r origin can be investigated. Since the introduction of this concept s ome 50 additional markers have been introduced. The recognition of tis sue factor pathway inhibitor (TFPI) has introduced a new concept in th e understanding of the plasmatic and vascular interactions. Tissue fac tor and its inhibitor can now be measured at fmol amounts in plasma an d body fluids. Specific antibodies to these markers can also be utiliz ed in immunocytometric and flow cytometric analysis and will provide v aluable diagnostic information. High through-put instruments and cost/ technologies compliance methodologies are available to provide afforda ble laboratory approaches in the new era of cost constraint diagnostic medicine. However, a major deficit in the educational programs still exists and warrants the development of these programs in medical and a llied health curriculums.