High incidence of intracranial haemorrhage in Egyptian children with congenital afibrinogenaemia

Introduction: Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality in patients with congenital afibrinogenaemia. Details on location of cerebral haemorrhage, management and neurological outcomes are lacking. Methods: We performed a retrospective study on Egyptian children with congenital afibrinogenaemia who experienced ICH, in order to estimate frequency, symptoms and neurological outcomes. Results: Among 58 children with congenital afibrinogenaemia treated on demand, 18 (31%) had an history of ICH (28 episodes). The first ICH occurred at a median age of 1 year (Q1-Q3 1-7 years). Impaired consciousness level, vomiting and seizures were the most common presenting symptoms. Spontaneous bleeding was associated with a more severe clinical presentation and worse neurological outcomes, including hydrocephaly and impaired cognitive development. Only half of ICH events (n = 14) were treated in less than 24 h from the onset of symptoms. Fibrinogen replacement by Fresh Frozen Plasma (FFP), cryoprecipitate or fibrinogen concentrates was administered in seven (25%), 19 (68%) and three (10%) ICH events, respectively. Overall, seven (25%) ICH occurring in four patients required a surgical intervention. After the ICH, six patients started secondary prophylaxis. The cumulative incidence of ICH at 10 years was 35% (95% CI 23-51) and at 20 years was 40% (95 CI% 26.7-58.8). Conclusion: In our cohort of children with congenital afibrinogenaemia, ICH was very frequent and associated with adverse neurological outcomes and death. Further studies are required to determine whether primary prophylaxis starting early in childhood is indicated after diagnosis.</p

Management of pregnancy and delivery in congenital fibrinogen disorders: communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen

Congenital fibrinogen disorders (CFDs) are a heterogeneous group of rare congenital quantitative and/or qualitative fibrinogen deficiencies. The spectrum of molecular anomalies is broad, leading to several subtypes of fibrinogen disorders (ie, afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia). Pregnancy in women with CFDs is a high-risk clinical situation, with an increased tendency for miscarriages, bleeding, and thrombosis. Even though it is well established that management of such pregnancies requires a multidisciplinary approach involving specialists (hematologists and maternal/fetal medicine experts with expertise in the management of inherited bleeding disorders), specific guidelines are lacking. In this International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee communication, we aim to propose an expert consensus opinion with literature evidence where available on the strategy for management of pregnancy, delivery, and puerperium in CFDs

Lysosomal Storage Disorders in Egyptian Children

To describe the spectrum, relative prevalence and molecular background of lysosomal storage disorders in Egypt.status: publishe

Clinical phenotype, fibrinogen supplementation, and health-related quality of life in patients with afibrinogenemia

Due to the low prevalence of afibrinogenemia, epidemiologic data on afibrinogenemia are limited, and no data are available on health-related quality of life (HRQoL). We conducted a cross-sectional international study to characterize the clinical features, the fibrinogen supplementation modalities, and their impact on HRQoL in patients with afibrinogenemia. A total of 204 patients (119 adults and 85 children) from 25 countries were included. The bleeding phenotype was severe: 68 (33.3%) patients having at least one bleed per month and 48 (23%) a history of cerebral bleeding. About 35% (n = 72) of patients were treated with fibrinogen concentrates or cryoprecipitates as prophylaxis, 18.1% (n = 37) received ≥1 injection per week, and 16.6% (n = 34) were on home treatment. A thrombotic event was reported in venous and/or arterial territories by 37 (18.1%) patients. Thrombosis occurred even in young patients, and recurrence was frequent (7.4%). The total HRQoL was lower in children than in adults. Discomfort linked to treatment and limitations to sports and leisure were the main concerns. Women and children were particularly affected in family relationships. In multivariate analyses, younger age, residence in Asia or Africa, and a previous thrombotic event were statistically correlated with a worse HRQoL. In summary, our study underlines the severe bleeding and thrombotic phenotype and their impact on HRQoL in afibrinogenemia. The optimal strategy for fibrinogen supplementation needs to be determined. This trial was registered at www.clinicaltrials.gov as #NCT03484065