Molecular Markers of Hemostatic Activation: Applications in the Diagnosis of Thrombosis and Vascular and Thrombotic Disorders

Abstract

The recognition of molecular marker events leading to hemostatic and thrombotic 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, fibrinolysis, kallikrein-kinin system, vascu— lar stress, and intercellular interactions result in the generation of cell/process specific markers of a pathophysiologic event. It has been two decades since the concept of molecular markers was first introduced in the diagnosis of hemostatic and thrombotic disorders. However, due to cost/technologic limitations and lack of understanding of this field at various levels its usage in clinical laboratory diagnosis was rather limited. With the advent of such analytical techniques such as enzyme-linked immunosorbent assays (ELISA) a disease specific molecular profiling can be readily accomplished. Subclinical activation of platelets, endothelial distress, and aberrations of the protease network can be readily diagnosed by utilizing specific assays. The concept of hypercoagulable state is now validated utilizing such markers of hemostatic activation such as platelet factor 4, thromboxane B₂, fibrinopeptide A and plasminogen activator inhibitor. Cardiovascular disease risk and blood vascular disorders can be diagnosed utilizing these markers. The monitoring of antithrombotic drugs that do not produce any anticoagulant effects on blood can also be readily accomplished by using some of these lanalytes. Using specific monoclonal antibodies, various diagnostic profiles for such disorders as thrombotic stroke, disseminated intravascular coagulation, primary fibrinolysis, hemodynamic disorders, and diseases of vascular origin can be investigated. Since the introduction of this concept some 50 additional markers have been introduced. The recognition of tissue factor pathway inhibitor (TFPI) has introduced a new concept in the understanding of the plasmatic and vascular interactions. Tissue factor and its inhibitor can now be measured at fmol amounts in plasma and body fluids. Specific antibodies to these markers can also be utilized in immunocytometric and flow cytometric analysis and will provide valuable diagnostic information. High through-put instruments and cost/technologies compliance methodologies are available to provide affordable 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 allied health curriculums. Key Words: Molecular markers—Hypercoagulable state—Enzyme-linked immunosorbent assay—Tissue factor pathway inhibitor— Tissue factor.