Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

Knowledge of signs, treatment and need for urgent management in patients presenting with an acute ischaemic stroke or transient ischaemic attack: a prospective study.

OBJECTIVE: To assess stroke awareness among patients presenting to the emergency department with an acute ischaemic stroke or transient ischaemic attack (TIA). METHODS: A consecutive cohort of patients presenting with a cerebrovascular event was prospectively enrolled over a 15-month period and questionnaires were administered. If the patient was unable to respond to the questions or answer the questionnaire, it was administered to the primary caregiver. Comprehension of having a cerebrovascular event, reason for delay in presentation, mode of arrival and knowledge of treatment modalities were determined. RESULTS: Only 42% of 400 patients thought they were having a stroke or TIA. The median time to presentation was 3.4 h. Delayed presentation was almost equal in men and women. When asked about onset, 19.4% thought that a stroke came on gradually and only 51.9% thought immediate presentation was crucial. 20.8% of patients had heard of thrombolysis. CONCLUSION: Community knowledge of ischaemic stroke needs to be enhanced so that individuals present earlier, leading to timely management.

Impact of acute blood pressure variability on ischemic stroke outcome.

BACKGROUND: The authors previously reported a low initial emergency department (ED) blood pressure (BP) to be associated with a significantly increased risk of death at 90 days. In this article, they examine the impact of acute BP variability following onset of ischemic stroke. METHODS: The study cohort consisted of 71 patients with stroke onset less than 24 hours. BP measurements were obtained every 5 minutes for the duration of the patient's ED stay. During the first 180 minutes, the median number of readings per patient was 9 (range 2 to 30). RESULTS: The baseline median systolic (sBP) and diastolic (dBP) BPs were not different for the patients that died within 90 days compared with those that were alive (p = 0.91 for sBP and p = 0.27 for dBP). Patients who died within 90 days had a greater differential in their dBP during the first 180 minutes than the patients that were alive after 90 days (median 44.5 vs 25 mm Hg; Wilcoxon rank sum test, p < 0.001). A similar result was observed for sBP (median 47 vs 30 mm Hg; p = 0.047). CONCLUSION: Wide fluctuation of blood pressure in the first 3 hours of the emergency department stay in patients with acute ischemic stroke appears to be associated with an increased risk of death at 90 days.