Platelet-Released Proteins as Molecular Markers for the Activation Process

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Abstract
The desire to have a specific, sensitive marker for platelet activation was originally thought to lie in the development of RIAs for BTG and PF4. Although this wish has not been denied, the interpretation of the information obtained from such an analysis has proved far less rewarding. The principal challenge of these procedures is based upon the lack of a cause and effect relationship between a given disease and platelet activation, coupled with the differential clearance rate and mechanism for each of the discussed proteins. Thus, we have seen that the renal clearance rate and mechanism for each of the discussed proteins. Thus, we have seen that the renal clearance of a patient should be noted prior to interpreting the elevation of BTG. Similarly, since PF4 is removed from the circulation so rapidly, its plasma values tend to be lower than BTG by a factor of 5, although the significance of the BTG to PF4 ratio is questioned. Administration of heparin results in a heparin-induced increase in plasma PF4 levels but not for BTG, and this PF4 increase can be as great as 20-fold. PF4 and BTG values are also directly increased by pressure increases. Taken individually, these mediators each compromise the ability to correlate the significance of platelet protein increases with any single pathologic condition. When viewed collectively, an analysis of platelet-released proteins is best interpreted as an indication that the functional integrity of the platelet has been perturbed; the direct relationship of disease processes to platelet release is far from certain and is simply documented by the use of such described procedures. The final note of caution for these assays is to be found in the recent summary analysis of the standardization of both BTG and PF4. In this study, considerably greater variation among laboratories was noted for PF4 than was seen for BTG, and the study directors concluded that comparisons of results between laboratories should be regarded as unreliable due mainly to the use of different standards for each protein in a given laboratory. The final note of caution for these assays is to be found in the recent summary analysis of the standardization of both BTG and PF4. In this study, considerably greater variation among laboratories was noted for PF4 than was seen for BTG, and the study directors concluded that comparisons of results between laboratories should be regarded as unreliable due mainly to the use of different standards for each protein in a given laboratory.

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