Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors

Abstract

Intracranial haemorrhage (ICH) is the most serious bleeding symptom in haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987-2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences. The cumulative hazard of ICH for the whole cohort over the entire follow-up period was 26.7 per 1000 patients, and the annualized rate of ICH was 2.50 events per 1000 patients (95% CI 1.90-3.31). The risk of ICH was higher in the youngest children (24.4 per 1000, 95% CI 12.7-47.0 in the first year of age and 14.9, 95% CI 7.1-31.4 in the second year of age) and then progressively rose again after the age of 40. Univariate, bivariate (age-adjusted) and multivariate analysis investigating the effects of patient characteristics on ICH occurrence showed that haemophilia severity and inhibitor status were strongly associated with ICH [severe vs. mild, HR 3.96 (2.39-6.57); inhibitor vs. non-inhibitor 2.52 (1.46-4.35)]. HCV infection was also associated with the risk of ICH [HR 1.83 (1.25-2.69)]. Therapeutic suggestions based upon our experience to control ICH recurrence are provided.

Clinical Characteristics and Prognostic Factors in Hemophiliacs with Intracranial Hemorrhage: A Single-Center, Retrospective Experience

“…In the present series, 3 (37.5 %, 3/8) developed neurological complications, including transient neurological abnormalities (blurred vision and dysarthria) and two patients achieved complete recovery from symptoms. Previous studies have shown variability in the incidence of long-term sequelae, ranging from 9.4 to 22.7 % [5,6,11,16]. This is also consistent with our results.…”

“…The mortality rate was 20.0 % (2/10) in our clinical series of patients. This is consistent with previous reports showing variability in mortality ranging from 0 to 25 % in patients with hemophilia presenting with ICH [5,6,11,16]. Two of our three patients who underwent neurosurgical intervention died, but this was likely the result of the ICH characteristics and patient conditions, not the neurosurgical intervention.…”

“…After treatment with FVIII and FIX concentrates became available in the late 1950s and 1960s, there was a dramatic decrease in mortality in patients with hemophilia A or B presenting with ICH from 70 % [9] to 20-30 % [10]. However, according to recent studies, the mortality rate of hemophiliacs with ICH is still about 20 % [3,11], and there has been no corresponding decrease in the mortality of patients with hemophilia presenting with ICH.…”

“…The incidence of ICH has been found to range from 2.2 to 7.5 % in patients with hemophilia [5,6,[12][13][14]. In one study, the cumulative hazard of ICH for the entire cohort over the comprehensive follow-up period was 26.7 per 1000 patients, and the annual rate of ICH was 2.50 events per 1000 patients (95 % CI = 1.90-3.31) [11]. Patients with hemophilia are 20 to 50 times more likely to develop ICH than the general population, with a reported prevalence of 2.7-12 % and an incidence of 290-748/10 5 patient-years [3][4][5][6].…”

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

“…pri okužbi z virusom HIV, je to lahko razlog za odločitev celo za 3-do 6-mesečno profilaktično zdravljenje (23,107,108).…”