Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives

Abstract

Hemophilia is a bleeding disorder that afflicts about 1 in 5000 males. Treatment relies upon replacement of the deficient factor, and response to treatment both in clinical research and practice is based upon subjective parameters such as pain and joint mobility. Existing laboratory assays quantify the amount of factor in plasma, which is useful diagnostically and prognostically. However, these assays are limited in their ability to fully evaluate the patient’s clot-forming capability. Newer assays, known as global assays, provide a far more detailed view of thrombin generation and clot formation and have been studied in hemophilia for about 10 years. They have the potential to offer a more objective measure of both the hemophilic phenotype as well as the response to treatment. In particular, in patients who develop inhibitors to deficient clotting factors and in whom bypassing agents are required for hemostasis, these assays offer the opportunity to determine the laboratory response to these interventions where traditional coagulation assays cannot. In this article we review the existing literature and discuss several controversial issues surrounding the assays. Last, a vision of future clinical uses of these assays is briefly described.

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

“…Despite the fact that TGA is a known marker for thrombotic risk, clinical application has been limited because of poor interlaboratory standardization of assay techniques. [58][59][60] However, both serum albumin and proteinuria severity have been epidemiologically linked to thrombotic risk. [13][14][15][16][17][18] Thus, if confirmed, proteinuria and/or serum Figure 5.…”

Reversal of Rivaroxaban-Induced Alterations on Hemostasis by Different Coagulation Factor Concentrates

“…35, 36 In contrast with PT, TG assays have proven useful in the evaluation of alterations of coagulation in severe congenital deficiencies, 37 although there is a reasonable concern on whether correction of alterations in the kinetics of TG in vitro assays could be predictive of a bleeding risk after new oral anticoagulants or its potential reversal. 38, 39 In our studies, effects of rivaroxaban were very evident when TG was activated through the extrinsic pathway (RCL reagent) and less evident when triggering the intrinsic pathway using the phospholipid-based activator (RD reagent).…”

Thrombin generation in different cohorts: Evaluation of the haemostatic potential

“…This prevalence corresponds to the prevalence found in the Caucasian population [58], and it was not deemed necessary to modify the CAT ® method by adding thrombomodulin.…”

“…Thrombin generation assays have gained increasing importance in diagnosis and follow-up of management in haemophilia [58]. Thrombin generation assays can be used to distinguish between different bleeding phenotypes in pa-tients with mild/moderate hemophilia A [59] or to predict the response when bypassing haemostatic agents are administered to patients who have haemophilia with inhibitors [60].…”