Factor VIII Half-Life and Clinical Characteristics of Severe Hemophilia A.

Introduction

Patients with severe hemophilia A have considerably different factor VIII half-lives. Whether this is associated with clinical characteristics has not been reported. The aim of this study was to describe the effect of half-life on the clinical characteristics of patients with severe hemophilia.

Patients and Methods

Patients were selected from a single-centre cohort of 214 patients with severe hemophilia, born between 1944 and 1995. To improve efficiency we measured factor VIII half-life in the patients with the most severe and the mildest clinical phenotypes of severe hemophilia. Patients were selected according to age at first joint bleed, annual joint bleed frequency, clotting factor consumption and radiological Pettersson scores.

A first blood sample was taken after a period of 72 hours in which the patient did not use factor VIII. After infusion with 50 IU factor VIII/kg, blood was collected at 15, 30 minutes and 1, 3, 5, 24, 30, 48 and 60 hours. From 1972 onwards, data on joint bleed frequency, clotting factor use and age at first joint bleed were collected from the patients’ files. Pettersson scores were performed at five-year intervals. For calculations of annual clotting factor use (IU/kg/yr) and number of joint bleeds per year, the last 5 years of follow-up were used. Linear regression analysis was used to assess the relation between clinical characteristics and factor VIII half-life.

Results

Factor VIII half-life was measured in 42 patients and ranged from 7.4–20.4 hours, with a median of 11.8 hours. One hour increase in factor VIII half life was associated with a decrease of 96 (SD 45) IU clotting factor use per kg per year (p<0.05). Joint bleed frequency was similar in patients with a shorter and a longer factor VIII half-life. Median number of joint bleeds was 2.9 per year (interquartile range (IQR) 1.1–4.4) in patients with a factor VIII half-life shorter than 12 hours and 2.6 per year (IQR 1.0–4.8) in patients with a factor VIII half-life longer than 12 hours (p=0.84). Patients with a factor VIII half-life shorter than 12 hours had a median Pettersson score of 52 points (IQR 12–61) and patients with a factor VIII half-life longer than 12 hours had a median Pettersson score of 29 points (IQR 16–52; p=0.90).

Conclusion:

Patients with a shorter factor VIII half-life need more clotting factor to prevent joint bleeds and subsequent arthropathy than patients with a longer factor VIII half-life.