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. 2022 Apr 1;11(7):1969.
doi: 10.3390/jcm11071969.

Intracranial Haemorrhage in Haemophilia Patients Is Still an Open Issue: The Final Results of the Italian EMO.REC Registry

Ezio Zanon  1 , Samantha Pasca  2 , Francesco Demartis  3 , Annarita Tagliaferri  4 , Cristina Santoro  5 , Isabella Cantori  6 , Angelo Claudio Molinari  7 , Chiara Biasoli  8 , Antonio Coppola  4 , Matteo Luciani  9 , Gianluca Sottilotta  10 , Irene Ricca  11 , Berardino Pollio  11 , Alessandra Borchiellini  12 , Alberto Tosetto  13 , Flora Peyvandi  14 , Anna Chiara Frigo  15 , Paolo Simioni  1
Affiliations

Intracranial Haemorrhage in Haemophilia Patients Is Still an Open Issue: The Final Results of the Italian EMO.REC Registry

Ezio Zanon et al. J Clin Med. .

Abstract

Background: Intracranial hemorrhage (ICH) is a highly serious event in patients with haemophilia (PWH) which leads to disability and in some cases to death. ICH occurs among all ages but is particularly frequent in newborns. Aim: The primary aim was to assess the incidence and mortality due to ICH in an Italian population of PWH. Secondary aims were to evaluate the risk factors for ICH, the role of prophylaxis, and the clinical management of patients presenting ICH. Methods: A retrospective-prospective registry was established in the network of the Italian Association of Haemophilia Centers to collect all ICHs in PWH from 2009 to 2019 reporting clinical features, treatments, and outcomes. Results: Forty-six ICHs were collected from 13 Centers. The ICHs occurred in 15 children (10 < 2 years), and in 31 adults, 45.2% of them with mild hemophilia. Overall, 60.9% patients had severe haemophilia (15/15 children). Overall ICH incidence (×1000 person/year) was 0.360 (0.270−0.480 95% CI), higher in children <2 years, 1.995 (1.110−3.442 95% CI). Only 7/46 patients, all with severe haemophilia, had received a prophylactic regimen before the ICH, none with mild. Inhibitors were present in 10.9% of patients. In adult PWHs 17/31 suffered from hypertension; 85.7% of the mild subjects and 29.4% of the moderate/severe ones (p < 0.05). ICH was spontaneous in the 69.6% with lower rate in children (46.7%). Surgery was required in 21/46 patients for cerebral hematoma evacuation. Treatment with coagulation factor concentrates for at least three weeks was needed in 76.7% of cases. ICH was fatal in 30.4% of the cases. Of the survivors, 50.0% became permanently disabled. Only one-third of adult patients received long term prophylaxis after the acute treatment. Conclusion: The results from our Registry confirm the still high incidence of ICH in infants <2 years and in adults, particularly in mild PWHs presenting hypertension and its unfavorable outcomes. The majority of PWHs were treated on-demand before ICH occurred, suggesting the important role of prophylaxis in preventing such life-threatening bleeding.

Keywords: haemophilia A and B; incidence; intracranial haemorrhage; mortality; risk factors.

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Conflict of interest statement

E. Zanon, S. Pasca, F. Demartis, A. Tagliaferri, C. Santoro, I. Cantori, A. C. Molinari, C. Biasoli, M. Luciani, G. Sottilotta, I. Ricca, B. Pollio, A. Borchiellini, A. Tosetto, A. C. Frigo, P. Simioni have no conflict of interest to diclose. A. Tagliaferri received fees as an advisory board member from Bayer and Roche, A. Coppola received fees as a consultant or invited speaker by Bayer, Novo Nordisk, and Sobi F. Peyvandi has received speaker fees for education meetings: Ablynx, Roche, Grifols, Takeda, Sanofi, Sobi, and Biomarin, and she is an Advisory Board Member of Sanofi, Roche, Takeda, Sobi, and Biomarin.

Figures

Figure 1
Figure 1
Concomitant diseases reported at ICH onset. 11 of 26 patients presenting other diseases had two or more comorbidities.
Figure 2
Figure 2
Intracranial haemorrhage (ICH) free survival probability in the different haemophilia degrees.
See this image and copyright information in PMC

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