Phenotypical variability in congenital FVII deficiency follows the ISTH-SSC severity classification guidelines: a review with illustrative examples from the clinic

Abstract

BackgroundOne of the most common rare inherited bleeding disorders, congenital factor VII (FVII) deficiency typically has a milder bleeding phenotype than other rare bleeding disorders. Categorizing severity in terms of factor activity associated with hemophilia (severe <1%, moderate 1%–5%, mild 6%–40%) has led to the observation that bleeding phenotype does not follow closely with FVII activity. Over the past decade, large-scale global registries have investigated bleeding phenotype more thoroughly. The International Society on Thrombosis and Haemostasis has reclassified FVII deficiency as follows: severe, FVII <10%, risk of spontaneous major bleeding; moderate, FVII 10%–20%, risk of mild spontaneous or triggered bleeding; mild, FVII 20%–50%, mostly asymptomatic disease.Case reportsEleven illustrative cases of congenital FVII deficiency adapted from clinical practice are described to demonstrate the variability in presentation and in relation to FVII activity levels. Severe FVII deficiency usually presents at a young age and carries the risk of intracranial hemorrhage, hemarthrosis, and other major bleeds. Moderate FVII deficiency tends to present later, often in adolescence and particularly in girls as they reach menarche. Milder disease may not be apparent until found incidentally on preoperative testing, during pregnancy/childbirth, or following unexplained bleeding when faced with hemostatic challenges.ConclusionIt is important for health care professionals to be aware of the new definitions of severity and typical presentations of congenital FVII deficiency. Failure to appreciate the risks of major bleeding, including intracerebral hemorrhage in those with FVII activity <10%, may put particularly young children at risk.

A Retrospective Analysis of Clinical and Laboratory Data of Patients with Factor VII Deficiency: A Single Centre Experience

“…1 We decided to adhere to the classification proposed by Jain et al with FVII:C below 1% corresponding to severe and 1 to 5% to moderate deficiency. 12 The additional cut-off set at 15% reflects, as clarified before, the suggested minimal level protecting from spontaneous bleeds. 3,5,10 The true haemostatic threshold of FVII activity is not known.…”

Diagnosis and treatment discussion of congenital factor VII deficiency in pregnancy: A case report

“…After further analysis of the reported cases, the most common conclusion is that the FVII activity level, FVII genotype, coagulation test, and bleeding history could not predict the bleeding risk of patients with FVIID[ 14 ]. In preliminary studies, some patients with FVII activity lower than 8% showed mild symptoms or no symptoms; 12 patients with no previous bleeding history and 44% FVII activity had delayed intracranial hemorrhage[ 5 ]. In this case, the activity of FVII fluctuated between 2.00%-6.30% and PT fluctuated between 38.2-62.10 s when the drug was not used.…”

“…The International Society of Thrombosis and Hemostasis classifies FVIID as follows: severe: FVII < 10%, with the risk of spontaneous bleeding; moderate: FVII 10%-20%, with the risk of mild spontaneous or trigger bleeding; mild: FVII 20%-50%, most of them are asymptomatic[ 5 ]. The Seven Treatment Evaluation Registry defined FVII activity among severe patients as ≤ 5%[ 6 ].…”

“…Patients with FVIID are usually asymptomatic but have the possibility of bleeding during invasive surgery. Severe bleeding often occurs in individuals with FVII activity less than 2% or below the normal standard[ 5 ].…”

The features of the mode of delivery in patients with congenital deficiency of coagulation factor VII: case reports

“…Эти факты дают основание усомниться в клинической значимости существующих классификаций гипопроконвертинемии в зависимости от плазменной активности FVII. Наиболее распространена классификация, предложенная Международной ассоциацией по тромбозу и гемостазу (The International Society on Thrombosis and Haemostasis, ISTH), согласно которой тяжелая форма характеризуется снижением активности FVII менее 10% и высоким риском больших спонтанных кровотечений и кровоизлияний; средней тяжестиактивностью фактора 10-20% с риском небольших спонтанных или спровоцированных кровотечений, легкая форма -активностью фактора 20-50% с отсутствием клинических проявлений [8].…”