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MOLECULAR MARKERS OF THROMBIN ACTIVATION
About 50% of patients who experience a thrombotic event do not have an identifiable defect in their hemostatic mechanism. However, the increased activity of the coagulation system generates increased amounts of thrombin. Because of its potency, the body has several mechanisms for down regulation (shutting down) of any thrombin that is generated. These mechanisms include activation of the anticoagulant Protein C pathway as well as formation of complexes in conjunction with natural heparins (TATs). Prior to having a thrombotic episode, patients exist in a prethrombotic or hyper coagulable state, which almost certainly results in increased thrombin production. An ability to detect this enhanced thrombin formation may prevent an actual thrombotic event if appropriate therapeutic measures are initiated. Thrombin itself is impossible to quantitate and so the use of surrogate markers is necessary. The biochemistry involved in the conversion of thrombin to active free thrombin has been elucidated. This is outlined as follows:
Since we cannot measure thrombin itself, then the measurement of F1+2 would be an excellent marker of thrombin generation. This is helped by the fact that F1+2 is not generated in vivo by any other mechanism. Fragment 1+2 has a half life of about 1 hour and is cleared from the bloodstream by the liver.
An ELISA assay for F1+2 is available which allows the laboratory to provide data in a timely manner. This information will be useful to clinicians in determining if a patient is in a hyper coagulable or prethrombotic state.
The assay also has therapeutic value. If a patient with elevated values is treated with anticoagulant drugs (Heparin or Coumadin), the F1+2 assay can be used to follow the efficiency of the drug treatment. After discontinuation of therapy, F1+2 serial measurements (e.g.: 2 wks, 4 wks, 8 wks) may detect if a patient is again becoming hypercoagulable.
In addition to F1+2, HEMEX Laboratories offers MOCA - Markers of Cascade Activation - which include F1+2, TATs (Thrombin AntiThrombin Complexes) and SFM (Soluble Fibrin Monomer) and can demonstrate thrombin generation that is compensated (normal SFM with elevated F1+2 &/or TATs) or decompensated which allows conversion of fibrinogen to fibrin (elevated SFM values).
The tests can be ordered through any hospital
or on an outpatient basis. Simply specify Fragment1+2 or MOCA and send
to HEMEX Laboratories.