Factor VII Deficiency In African American Individuals. Presentation, Diagnosis and Management.A Single Medical Center Experience

Abstract

Background Factor VII (FVII), a vitamin K-dependent glycoprotein serine protease, is produced by the liver and plays a fundamental role in the activation of the extrinsic coagulation pathway. Hereditary factor VII deficiency is a rare coagulation disorder with autosomal recessive inheritance and an approximate prevalence of 1:500,000. Clinical manifestations vary from no symptoms to severe bleeding events and often correlate poorly with plasma levels of factor VII. Therapy for factor VII deficiency depends on the severity and the type of bleeding and includes fresh frozen plasma (FFP), antifibrinolytics and recombinant factor VIIa (rFVIIa). Recent data from the STER registry suggests that bleeding symptoms on presentation and factor VII activity level can be used to identify clinical variants and guide replacement therapy. The majority of patients enrolled in this registry were from European countries. Patients of African American origin remain poorly characterized. Aims We present our experience with diagnosis and management of patients, predominantly African American, in a large academic institution. We retrospectively reviewed the data on seven patients diagnosed with isolated factor VII deficiency and their management. Results Six of the seven patients followed in our institution were African American. Of them, three were female and three were male. A six month old girl was diagnosed during treatment for sepsis. She had no bleeding symptoms (FVII activity 27% on presentation, 32% one month later). The other two female patients presented with obstetrical bleeding (FVII <3% and 11% respectively). Of the male patients, two six year old twins had epistaxis (FVII activity 12%). Another six year old boy presented with trauma-associated hemorrhage, but had no prior history of bleeding (FVII 4%). Follow up data were available on five of the patients. Duration of follow up ranged from 6 months to more than 10 years. None of the patients had spontaneous bleeding, regardless of their presentation or level of FVII activity. The patients with bleeding and those who needed surgery received FFP (two patients prior to making the diagnosis) and rFVIIa (four patients). The doses used were 10-25mcg/kg in one or two applications. No bleeding and no thrombotic complications were observed with this therapy. None of the patients received antifibrinolytics. The one White Caucasian patient was a 25 year old male who presented with bleeding after trauma (FVII activity was 10%) and was managed with rFVIIa (25mcg/kg). Conclusion Our data demonstrates that, in African American patients, factor VII deficiency presents with variable clinical findings. There was poor correlation between the FVII levels and the clinical phenotype. Management with rFVIIa, used at the time of surgery or trauma at low to intermediate doses, was sufficient to prevent bleeding and was not associated with any significant complications. Disclosures: No relevant conflicts of interest to declare.