Asymptomatic Factor VII Padua in African Americans.

Abstract

Background: Symptomatology in congenital human FVII deficiency with FVII:C (Factor VII Coagulant Activity) levels < 1% ranges from asymptomatic to severe hemorrhagic problems. Additionally, FVII:C differs markedly depending upon the source of tissue factor (TF) in the thromboplastin utilized for measuring FVII:C. FVII deficiency reported in 1978 in patients from Padua, Italy was later shown to be associated with an arginine (R) to glutamine (Q) mutation at FVII amino acid 304. A study by Triplett et al. from 1985 reported FVII deficiency in 26 patients including 16 Caucasians, 1 Hispanic and 9 blacks. Of these patients, all 9 black patients were asymptomatic whereas the other 17 patients had a clinically relevant bleeding disorder. Since that time there have been no reports describing the genetic cause of FVII deficiency in asymptomatic African American individuals. Methods: Plasma was obtained from patient blood samples obtained in 3.2% sodium citrate. FVII:C levels were performed using one-stage clotting assays with either rabbit brain thromboplastin (Simplastin Excel, Biomerieux, Durham, NC) or lyophilized recombinant human TF (Innovin, Dade Behring, Inc., Newark, DE). Factor VII antigen levels (VII:Ag) were measured using an enzyme-linked immunoabsorbent assay (American Bioproducts Co, Parsippany, NJ). A normal pool was constructed by mixing equal volumes of plasma from greater than 20 healthy control subjects. Results Patient # Prothrombin Time in seconds FVII:C Simplastin Excel FVII:C Innovin FVII:Ag Genotype Phenotype 1-African American 15.6 16% 33% 61% Heterozygote R304Q Minor Nose Bleeds 2- African American Prolonged 26% 54% 67% Heterozygote R304Q Asymptomatic for bleeding 3- African American 14.5 21% 64% NA Heterozygote R304Q Asymptomatic for bleeding Conclusions: We show that FVII deficiency in three asymptomatic African American patients at our specialty laboratory was due to FVII-Padua (R304Q). An additional ten African American patients showed prolonged prothrombin times and FVII:C values consistent with the laboratory phenotype of FVII-Padua. This diagnosis prevented inappropriate blood transfusions prior to surgery in several of these patients.

Factor VII Padua in Iran: clinical and laboratory findings of three unrelated patients

“…In accordance with previously reported data, our cases with Padua variant could be classified into two groups: asymptomatic patients (pedigree A), if do not consider easy bruising because of the unreliability of this symptom as reported by the patients; and paucisymptomatic patients with a history of mild-to-moderate bleeding, who presented easy bruising, epistaxis, gingivorrhagia, bleeding after surgical challenges (including dental extraction and tonsillectomy) (pedigrees B and C). Moreover, a number of studies have shown that heterozygous and homozygous Padua mutation could be associated with clinical symptoms like easy bruising, epistaxis, oral cavity bleeding, and abundant menstruations [24][25][26], but the majority of subjects with Padua variant in heterozygous and homozygous state are asymptomatic [4,27]. Like platelet function disorders and the majority of patients with FVII deficiency, our patients also had the minor bleeding manifestations [28].…”