Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists

M. L. Y. de Koning, K. Fischer, B. de laat, A. Huisman, M. Ninivaggi, R. E. G. Schutgens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Background: It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective: To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods: In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII <1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) >= 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nM*min) was compared according to FVIII level (<1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (>= 2.0). Medians and interquartile ranges (IQRs) were calculated. Results: Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP <400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP <400. Conclusion: In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

Original languageEnglish
Pages (from-to)868-875
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume15
Issue number5
DOIs
Publication statusPublished - May 2017

Keywords

  • atrial fibrillation
  • coumarins
  • factor VIII
  • hemophilia A
  • thrombin
  • INTERNATIONAL-NORMALIZED-RATIO
  • CORN TRYPSIN-INHIBITOR
  • CALIBRATED AUTOMATED THROMBOGRAPHY
  • FACTOR-VIII DEFICIENCY
  • ATRIAL-FIBRILLATION
  • LIFE EXPECTANCY
  • CARDIOVASCULAR-DISEASE
  • ANTICOAGULANT-THERAPY
  • CLINICAL SEVERITY
  • PLASMA

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