Molecular markers of hemostatic disorders: implications in the diagnosis and therapeutic management of thrombotic and bleeding disorders.

With current technological advances, it is now possible to measure in less than 50 microL of plasma picomolar amounts of circulating products of platelet activation, products of protease activation related to coagulation and fibrinolytic pathways, and prostaglandin metabolites formed during a physiologic or pathologic process. Most of these markers, which circulate in blood in nanogram or picogram amounts per milliliter during or after pathologic activation, provide pertinent information on the status of a patient in terms of specificity and early detection, and will be of crucial value in the diagnosis of hemostatic defects and the management of newer antithrombotic drugs that cannot be monitored by currently available assays. Currently, 125I- and 3H-based simple radioimmunoassays are available for platelet factor 4, beta-thromboglobulin, fibrinopeptide A, B beta 15-42 related peptides, thromboxane B2, and the prostaglandins 6-keto-PGF1 alpha and PGE2. Nonisotopic methods such as enzyme-linked immunosorbent assays and fluoroimmunoassays are being developed. Serotonin and ADP, products of platelet activation, are measurable by liquid-chromatographic, immunoenzymatic, and spectrophotofluorometric methods. Analytical methods for fibrin split products (fragments D and E) and serine protease inhibitor complexes such as thrombin-antithrombin-III, factor Xa-antithrombin-III, and kallikrein-C1-esterase are also being developed. We have evaluated all of these methods and found them to be very sensitive to those components of endogenous activation of the hemostatic system listed above.