Characterization and Diagnostic Work-up of a Patient with Functionally Impaired Platelet GP6

Introduction

Platelet function assays are commonly used diagnostic tools in patients with suspected inherited or acquired hemostatic disorders, and to monitor the efficacy of anti-platelet medication.[1] [2] Beside different newer point-of-care assays, such as the platelet function analyzer (PFA) or the whole blood aggregometry (WBA),[3] [4] the classical Born's light transmission platelet aggregometry (LTA) is an indispensable diagnostic tool for hemostaseologists and therefore still frequently performed in specially equipped laboratories.[5] For routine testing of platelet function by the LTA assay, the patient's platelet rich plasma (PRP) is mixed with different platelet activating agonists, such as ristocetin, ADP, collagen, and arachidonic acid.[5] In few patients, testing their PRP by the LTA assay leads to an isolated missing response in the collagen-induced aggregation, while the platelets respond normally to all the other agonists.[6] [7] [8] Regarding the collagen-induced aggregation, the platelet membrane glycoprotein VI (GP6) plays a central role.[9] [10] It is expressed as a complex with the Fc receptor γ-chain (FcRγ) and has been identified as the main physiological platelet receptor for collagen.[11] When collagen binds to GP6, an activation cascade is initiated by tyrosine phosphorylation inducing the formation of a complex of signal-transducing proteins.[11] The collagen/GP6 interaction finally leads to a physiologic activation of platelets, which can be measured in vitro by the formation of platelet aggregates from PRP. On the other hand, in patients with bleeding tendency displaying a negative collagen reaction in the LTA assay but positive results for all other agonists including arachidonic acid, an acquired or inherited functional defect of GP6 could be the possible cause of the bleeding disorder.[12] [13] [14] [15] [16]

In this case report of a female patient suffering from a clinically mild bleeding disorder, we describe the complexity of the respective diagnostic work-up to elucidate a suspected functional GP6 defect.

• References

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