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

Abstract

Due to its low prevalence, epidemiologic data on afibrinogenemia are limited and none 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 more than one 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 conclusion, 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.

Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

“…The prevalence was similar in women (54%) and men (46%) below the age of 60 years, and the prevalence was similar amongst all age groups [34]. According to the latest published cross-sectional international study, quality of life was recorded overall 204 patients with afibrinogenemia from 25 countries, of which more than 50% of patients came from Asia [35]. In populations with frequent consanguineous marriages, the prevalence of afibrinogenemia, like the occurrence of other disorders of hemostasis with autosomal recessive inheritance, is increased [2].…”

“…It was documented that patients with low fibrinogen activity have higher occurrence of unprovoked major bleeding events, while patients with sufficient fibrinogen activity were asymptomatic [37]. Except these potentially life-threatening complications, the most frequent manifestations of afibrinogenemia are mucosal bleeding, especially menorrhagia, epistaxis, and bleeding in the oral cavity [35,39]. Musculoskeletal bleeding (and also bleeding into the joints) is reported in approximately half of the individuals with afibrinogenemia [1,39,40], and in some studies, it was more prevalent than bleeding from mucosal surfaces.…”

Afibrinogenemia with two compound heterozygous mutations in FGA gene

“…1 is, epistaxis, gingivorrhagia and menorrhagia. 3 Besides, about half of patients could suffer from muscular bleeding or hemarthrosis like in severe haemophilia. 3 More rarely, gastrointestinal, urinary tract and intracranial bleedings have been described.…”

“…3 Besides, about half of patients could suffer from muscular bleeding or hemarthrosis like in severe haemophilia. 3 More rarely, gastrointestinal, urinary tract and intracranial bleedings have been described. 1 Spontaneous abortions are reported in women with afibrinogenemia without fibrinogen supplementation and the risk of antepartum/postpartum bleeding is high.…”

“…Paul Billoir 1 Alessandro Casini 2 M. Neerman-Arbez 3 Virginie Barbay 1,4 Pierre Chamouni 4 Pascale Schneider 5 Véronique Le Cam Duchez 1,4…”