ArticleJournal of thrombosis and haemostasis : JTH2020
Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Intrinsic activated thrombin generation for treatment efficacy and monitoring of octocog alfa and emicizumab in severe hemophilia A.Research and practice in thrombosis and haemostasis · 2026Article
- Plasmin generation analysis in patients with bleeding disorder of unknown cause.Blood advances · 2024Article
- Pharmacokinetic-Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF/FVIII Concentrate.European journal of drug metabolism and pharmacokinetics · 2024Article
- Perturbations in kinetics of the thrombin generation assay identify women at risk of preeclampsia in the first trimester and provide the rationale for a preventive approach.American journal of obstetrics and gynecology · 2023Article
- In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype.Research and practice in thrombosis and haemostasis · 2023Article
- Thrombin generation and implications for hemophilia therapies: A narrative review.Research and practice in thrombosis and haemostasis · 2023Review
- Combining factor VIII levels and thrombin/plasmin generation: A population pharmacokinetic-pharmacodynamic model for patients with haemophilia A.British journal of clinical pharmacology · 2022Article
- Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review.Journal of thrombosis and haemostasis : JTH · 2022Review
- Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases.Frontiers in cardiovascular medicine · 2022Review
- Low-dose immune tolerance induction therapy in children of Arab descent with severe haemophilia A, high inhibitor titres and poor prognostic factors for immune tolerance induction treatment success.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Clinical use of thrombin generation assays.Journal of thrombosis and haemostasis : JTH · 2021Review
- Assessing Plasmin Generation in Health and Disease.International journal of molecular sciences · 2021Review
- Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation.Journal of thrombosis and haemostasis : JTH · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinical severity of hemophilia A (HA) varies, possibly due to interplay of many factors in the hemostatic pathway. Pharmacokinetic monitoring of factor VIII (FVIII) replacement therapy in HA patients consists of measuring FVIII activity levels and subsequent dose adjustment. The Nijmegen Hemostasis Assay (NHA) measures thrombin generation (TG) and plasmin generation (PG).
objectiveTo determine differences in TG and PG between HA patients before and during a pharmacokinetic study and identify best parameters to develop a pharmacodynamic model.
methodsTwenty-five HA patients (baseline FVIII < 1-9 IU/dL) underwent a pharmacokinetic study with a single dose of 25-50 IU/kg standard half-life FVIII concentrate. At baseline and after administration of FVIII TG and PG parameters were measured with the NHA.
resultsFVIII activity level increased from median 1.0 IU/dL (interquartile range < 1.0-6.0) to 71 IU/dL (62-82) 15 minutes after administration and decreased to 15 IU/dL (10-26) at 24 hours. TG was enhanced simultaneously, with thrombin peak height (TPH) increasing from 22nM (15-35) to 222nM (159-255), and thrombin potential (TP) from 404nM/min (undetectable-876) to 1834nM/min (1546-2353). Twenty-four hours after infusion, TG parameters remained high (TPH 73nM [58.5-126.3]; TP 1394nM/min [1066-1677]) compared to FVIII activity level. PG showed hyperfibrinolysis in severe HA patients compared to mild patients and controls, which normalized after FVIII supplementation.
conclusionHA patients showed clear differences in baseline TG and PG despite having comparable FVIII activity levels. These results reveal a discrepancy between FVIII activity level and TG, in which the latter may be a better parameter to monitor individualized treatment in HA patients.
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