Mechanisms, markers and management of coagulation activation.

Sensitive and specific laboratory methods are now available to detect and diagnose states of coagulation activation, defined as a procoagulant imbalance between the production and inhibition of enzymes in the coagulation system short of fibrin deposition. Although most coagulation enzymes cannot be measured specifically and accurately, assays for activated factor XII and factor VII have recently become available. Activated protein C, the active enzyme of a major anticoagulant pathway, can also be measured. Indirect approaches to the detection of coagulation activation are to measure the plasma levels of peptides released from coagulation zymogens when they are converted into active enzymes and the stable complexes formed in plasma when such enzymes are neutralized by their naturally-occurring inhibitors. These assay methods have dramatically improved our understanding of the mechanistic role of coagulation activation in health and disease. However, their clinical predictive value and usefulness for choosing and monitoring antithrombotic therapy still need to be defined in prospective clinical studies.