scholarly journals Inhibitor in Congenital Factor VII Deficiency; a Rare but Serious Therapeutic Challenge—A Systematic Literature Review

2021 ◽  
Vol 10 (2) ◽  
pp. 211
Author(s):  
Nahid Ramezanpour ◽  
Farhad Zaker ◽  
Arijit Biswas ◽  
Akbar Dorgalaleh
Keyword(s):  
Literature Review ◽  
Replacement Therapy ◽  
Systematic Literature Review ◽  
Factor Vii ◽  
Inhibitor Development ◽  
Therapeutic Challenge ◽  
Clinical Presentations ◽  
Life Threatening ◽  
Fvii Deficiency ◽  
Congenital Factor

Background: Congenital factor (F) VII deficiency is a rare coagulation factor deficiency with an estimated incidence of 1 per 500,000 individuals. Patients with severe FVII deficiency present a broad range of clinical presentations. Alloimmunization against exogenous FVII, as the main challenge of replacement therapy, is an extremely rare phenomenon that is accompanied by a high rate of life-threatening bleeding, that renders replacement therapy less effective. Due to the importance of the issue, we performed a systematic literature review in order to assess incidence, molecular basis, clinical presentations, and therapeutic challenge and management of inhibitor in congenital FVII deficiency. Strategy of search: This systematic review was performed in accordance with PRISMA guidelines. We performed an English-language literature review in the PubMed, EMBASE, Scopus, and Google Scholar databases, using the following keywords: “factor VII inhibitor”, “factor VII inhibitors”, “FVII inhibitors”, “congenital FVII deficiency”, “recombinant factor VII”, “anti rFVIIa”, “replacement therapy”, and “alloantibody”. Results: Out of 380 patients in the 13 studies, 27 had inhibitor against FVII; 18 were male, 7 were female, while the sex of 2 was not stated. The majority (92%) developed a high-titer inhibitor (Bethesda Unit > 5). All patients had severe FVII deficiency (FVII:C < 10%), and the majority received recombinant FVII prior to inhibitor development (N: 24, 89%). Among ten patients with a detected mutation, three subjects had a common non-sense (30%), and two had a deletion (20%). Conclusions: Inhibitor development is a relatively rare phenomenon seen only in severe FVII deficiency, where it is associated with severe and life-threatening presentations, treatment challenge, and economic burden on the patients and their families.

scholarly journals Novel IVS7+1G>T mutation of life-threatening congenital factor VII deficiency in neonates

Medicine ◽  
2019 ◽  
Vol 98 (40) ◽  
pp. e17360
Author(s):  
Juan He ◽  
Wei Zhou ◽  
Hui Lv ◽  
Li Tao ◽  
XiaoWen Chen ◽  
...  
Keyword(s):  
Factor Vii ◽  
Factor Vii Deficiency ◽  
Life Threatening ◽  
Congenital Factor

Factor VII Deficiency in the Negev - a 10 Years' Experience of One Tertiary Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4695-4695
Author(s):  
Yariv Fruchtman ◽  
Miri Ben harosh ◽  
Joseph Kapelushnik ◽  
Julia Mazar ◽  
Gili Kenet ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Residual Activity ◽  
Factor Vii ◽  
Bleeding Disorders ◽  
Factor Vii Deficiency ◽  
Advisory Boards ◽  
Wide Range ◽  
Tertiary Center ◽  
Life Threatening ◽  
Fvii Deficiency

Abstract Inherited factor VII (FVII) deficiency is the most common among the autosomal recessive rare bleeding disorders, with an estimated prevalence of 1:300,000 in European countries. Affected individuals display a wide range of clinical phenotypes, ranging from mild non spontaneous bleeding to life threatening (i.e. central nervous system[CNS] bleeding, gastrointestinal [GI] bleeding or haemarthrosis), whereas up to one-third of individuals with a FVII deficiency are asymptomatic and are mainly diagnosed during family studies or after screening for surgery. Unfortunately, the residual activity of FVII does not predict the individual propensity to bleed, and even in individuals with the same mutation, differences in clotting phenotypes can be seen. As our tertiary center serves a unique population in the Negev, we aimed at studying the prevalence and phenotype of FVII deficiency within the last decade. Methods: We searched all electronic records for the last 10 years depicting rare bleeding disorders by ICD 9 code - 2863 and compared them to the hematologic record of factor VII deficiency depicted in our lab - 50% or less activity. Patients with any record of genetic diagnosis, were compared with clinical findings. Results: The population in the Negev is estimated as 700000 people Most of them are Jewish and 150000 of them are Arab-Bedouins. We found 800 records of rare bleeding disorders (ICD 9-2863), Including 200 with FVII deficiency - 100/200 had FVII levels below 50%. Most (90%) of cases were of Jewish origin (mostly oriental Jews) and only 10% were Arab- Bedouins. Forty patients were asymptomatic with 50-30% FVII activity and 20 patients with 30-10% FVII activity were either asymptomatic or presented with mild bleeding diathesis. Out of 23 cases with lower than 10% FVII activity, 7 were symptomatic and suffered severe life threatening bleedings (2 infant died of perinatal ICH. Five families (3 Bedouin and 2 oriental Jews) were identified with severe FVII deficiencies. The 4 Bedouin patients were identified to be homozygous to unique mutation. Interestingly, most medical records depicted FVII deficiency were of women studies due to fertility problems. Conclusions: The prevalence of FVII deficiency depicted in the Negev is much higher in comparison to literature reports (200/700000) Severe FVII deficiency was found in 23: 700000, consistent with 1: 30000 prevalence. As patients are highly variable, in order to "tailor" treatments according to disease severity, new directions should be pursued to identify those with the most severe phenotypes. Disclosures Kenet: Bayer, Novo Nordisk: Other: Advisory Boards, Speakers Bureau; Opko Biologics: Consultancy, Other: Advisory Boards; BPL; Baxelta: Research Funding; Pfizer: Honoraria.

scholarly journals Replacement therapy for bleeding episodes in factor VII deficiency

2013 ◽  
Vol 109 (02) ◽  
pp. 238-247 ◽  
Author(s):  
Mariasanta Napolitano ◽  
Alberto Dolce ◽  
Rosario Perez Garrido ◽  
Angelika Batorova ◽  
Mehran Karimi ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Ad Hoc ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Coagulant Activity ◽  
Fresh Frozen ◽  
Traumatic Bleeding ◽  
Bleeding Episodes ◽  
Fvii Deficiency ◽  
Using Data

SummaryPatients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1–20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one postrFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single ‘intermediate’ doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Clinical phenotypes and factor VII genotype in congenital factor VII deficiency

2005 ◽  
Vol 93 (03) ◽  
pp. 481-487 ◽  
Author(s):  
Guglielmo Mariani ◽  
Falko Herrmann ◽  
Alberto Dolce ◽  
Angelika Batorova ◽  
Daniela Etro ◽  
...  
Keyword(s):  
Severe Disease ◽  
Factor Vii ◽  
Early Management ◽  
Clinical Phenotypes ◽  
Functional Polymorphisms ◽  
Congenital Deficiency ◽  
Life Threatening ◽  
Multi Center Study ◽  
The Relationship ◽  
Congenital Factor

SummaryTo investigate the relationship between clinical phenotype, clotting activity (FVIIc) and FVII genotype, a multi-center study of factor VII (FVII) congenital deficiency with centralized genotyping and specific functional assays was carried out. FVII mutations characterized in patients (n=313) were extremely heterogeneous (103 different, 22 novel). Clinical phenotypes ranged from asymptomatic condition, including 15 homozygotes and 14 double heterozygotes, to patients with a severe disease char-acterized by life-threatening and disabling symptoms (CNS, GI bleeding and hemarthrosis) strongly associated with an early age of presentation. Based on type and number of symptoms we classified 90 'severe' (median FVIIc 1.4%, IQR [Interquartile Range] 0.9–3.8), 83 'moderate' (FVIIc 3%, IQR 1–21.7), and 140 'mild' bleeders (FVIIc 14%, IQR 3–31). The significantly different FVIIc levels, and the decreasing prevalence of homozygotes or double heterozygotes among severe (98%), moderate (84%) and mild (56%) bleeders, further support our classification. The excess of females among moderate bleeders (female/male ratio =2.6) is attributable to menorrhagia. There was no evidence for modulation of clinical features by frequent functional polymorphisms. Homozygotes for the same mutation (Ala294Val; 11125del C) with similar FVIIc and FXa generation levels, showed striking differences in clinical phenotypes. Our study depicts the ample clinical picture of this rare disorder, proposes a severity classification and provides arguments for the early management of the disease in the severe cases. Genotype-phenotype relationships indicate the presence of major environmental and/or extragenic components modulating expressivity of FVII deficiency.

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