Prediction of individual factor VIII or IX level for the correction of thrombin generation in haemophilic patients

Abstract

The TG assay could be used to determine in vitro the patient-specific factor VIII or IX level to be reached to effectively normalize their TG. These in vitro results should be confirmed by ex-vivo studies.

Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation

“…This patient showed a normalization of thrombin potential (90%-100% of normal) while thrombin peak height was only 50% of normal, proving the individual response of TG to FVIII supplementation. 25,26 Most interesting in this patient is the elevation of TG after 24 hours, which occurred with both products, with an interval of 6 years. This effect can possibly be explained by cellular and/or platelet alteration due to TG activation, for example because of microRNA expression and influence on other pro-and anticoagulation factor expression.…”

“…It was 46 nmol/L (28-55) in severe HA patients, but 32 nmol/L in moderate patients and 24 nmol/L (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) in mild patients, indicating higher plasmin production in severe HA patients than in mild HA patients (P = .02), and even more pronounced when severe patients are compared to normal controls (28 [21.5-34], P < .001). In Figure S2 in supporting information remaining TG and PG parameters are shown.…”

“…25 This is in accordance with another study that showed a high inter-individual heterogeneity in baseline TG parameters in hemophilia A and B patients, but after spiking plasma with the specific coagulation factor, TG showed strong correlations in individual patients. 26 The main drawback of these previous studies is the limited number of patients in whom TG was measured (12 and 10 HA patients, respectively). 25,26 In this study, we performed PK analysis in a cohort of severe, moderate, and mild HA patients, and combined these with measurement of TG and plasmin generation (PG) using the Nijmegen Hemostasis Assay (NHA).…”

“…26 The main drawback of these previous studies is the limited number of patients in whom TG was measured (12 and 10 HA patients, respectively). 25,26 In this study, we performed PK analysis in a cohort of severe, moderate, and mild HA patients, and combined these with measurement of TG and plasmin generation (PG) using the Nijmegen Hemostasis Assay (NHA). The NHA is developed to simultaneously measure TG and PG in a single assay by a fluorimeter, thereby incorporating the interplay between TG and PG.…”

Laboratory monitoring of hemophilia A treatments: new challenges

“…First, it is yet unclear how well the individual thrombin generation potential in vitro correlates with the actual hemostatic response in a patient (ie, whether these assays accurately predict clinical outcome). [57][58][59][60][61] Second, these global assays will not give information about the true FVIII equivalence of the agent. This is easily illustrated by using emicizumab as an example.…”