title: Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists.
abstract: Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: 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 (203-430) 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.
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: M L Y
authors.initials: MLY
authors.lastname: de Koning
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Synapse, Maastricht, the Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: de Laat
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Huisman
authors.affiliation: Synapse, Maastricht, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Ninivaggi
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: R E G
authors.initials: REG
authors.lastname: Schutgens
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006467:Hemophilia A / Q000097:blood* / Q000175:diagnosis; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D019934:International Normalized Ratio; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D013917:Thrombin; D000074:Acenocoumarol; D010644:Phenprocoumon
keywords: atrial fibrillation; coumarins; factor VIII; hemophilia A; thrombin