Abstract
Platelet-dependent thrombin generation is a helpful tool to assess ex vivo the interaction between platelets and plasma coagulation factors in the initiation, amplification, and inhibition of thrombin generation (TG). This review article discusses the most relevant available data on the clinical applications of fluorogenic TG, the most widely used TG assay, performed in the presence of platelets, i.e., in platelet-rich plasma. With respect to prothrombotic states, arterial hypertension and obesity were the most prominent cardiovascular conditions linked to increased platelet-dependent TG. In addition, platelet-associated hypercoagulability, assessed by the TG assay, has been shown in individuals with active cancer. In terms of bleeding, platelet-dependent TG has been applied to assess bleeding risk in individuals with hemophilia, von Willebrand disease, and Glanzmann thrombasthenia as well as in subjects with other congenital or acquired coagulation factor deficiencies. In addition to risk prediction, a role of the TG assay has been suggested in monitoring antiplatelet therapy in prothrombotic conditions and replacement therapy in bleeding diathesis. Finally, for the routine clinical use and as a biomarker of disease development and progression, better standardization and clinical validation of platelet-dependent TG are still needed.
Highlights
Thromboembolic disease and bleeding, representing two sides of the same coin, have been traditionally investigated by using different laboratory approaches
Results on thrombin generation (TG) in platelet-rich plasma (PRP) in patients with factor XI (FXI) deficiency demonstrated the ability of the assay to distinguish severe bleeding from non-bleeding individuals, which was independent of the FXI activity levels
The suggestion that the contradictory findings might be due to differences in assay/sample conditions is strengthened by the work of Pike et al, who showed that optimal differentiation in bleeding phenotype in FXI deficiency can be achieved by measuring TG in the presence of platelets when contact activation is inhibited [48]
Summary
Thromboembolic disease and bleeding, representing two sides of the same coin, have been traditionally investigated by using different laboratory approaches. The thrombin generation (TG) assay has emerged as a global coagulation tool that can assess both hypercoagulable and hypocoagulable conditions [3]. It can be performed in the absence of platelets, i.e., platelet-poor (PPP) and platelet-free plasma (PFP), and in the presence of platelets, i.e., platelet-rich plasma (PRP). TG in PRP enables the investigation of interactions between platelets and coagulation factors in plasma, representing an assay that closely mimics in vivo conditions [4]. The calibrated automated thrombogram (Thrombinoscope BV, Maastricht, The Netherlands), the most frequently used TG assay, employs a standardized testing procedure where
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