A Spectrum of Clinical and Laboratory Findings and Treatment Modalities in Patients with Factor VII Deficiency- A Single Medical Center Experience,

Factor VII, a vitamin K dependent glycoprotein serine protease secreted by the liver, has a fundamental role in the activation of the extrinsic coagulation pathway. It is found in the plasma as a zymogen, and is activated by tissue factor and calcium. Hereditary factor VII deficiency is a rare coagulation disorder with autosomal recessive inheritance found approximately at a prevalence of 1:500,000. In Israel, factor VII deficiency is found mostly in Sephardic Jews of Iranian, Moroccan and Tunisian origin as well as in the Druze population. Bleeding symptoms usually occur in homozygotes or compound heterozygotes. In symptomatic patients, the clinical severity of bleeding ranges from mild to severe (such as intracranial bleeding) and does not always correlate with plasma levels of factor VII activity. However, patients with factor VII activity of less than 1% may present with symptoms similar to severe hemophilia. Patients with factor VII activity of 5% or more usually present with milder bleeding such as epistaxis, gingival bleeding, menorrhagia or bruising. Therapy for factor VII deficiency depends on severity and type of the bleeding. Treatment includes fresh frozen plasma (FFP), tranexamic acid and recombinant factor VIIa (Novoseven).

The study goal was to find correlation between level of factor VII activity, bleeding complications and treatment modalities that were used in symptomatic patients or in those undergoing surgical procedures.

We performed a retrospective study of 125 patients with decreased levels of factor VII, referred to our department between 1990–2010. 56 patients with isolated deficiency of factor VII were included in the study. Patients with combined deficiencies or liver disease were excluded. Demographics, clinical symptoms and their correlation to levels of factor VII, as well as treatment modalities were investigated. A factor VII activity level below 50 % was considered as decreased. The data collection was performed after approval of hospital Helsinki committee.

Of 56 patients with isolated factor VII deficiency there were 29 males and 27 females. 31/56 (55.4%) of the patients were Jews of Sephardic origin. 18/56 (32%) of the patients had relatives with known factor VII deficiency. The activity of factor VII ranged from <1%-49%. There was no significant difference in factor VII activity levels between the symptomatic (mean = 20.87, SD = 17.9) and the asymptomatic patients (mean = 23.13, SD = 17.4). 11/56 (19.6%) of the patients had clinical symptoms of bleeding, 6 of them had factor VII level<10 %. No life threatening bleeding was reported. Most episodes of bleeding related to factor VII deficiency were epistaxis and menorrhagia. Less common bleeding included hematoma and gingival bleeding. Only 9% of the symptomatic patients required treatment with FFP or tranexamic acid. Recommendation for prophylactic treatment such as FFP and/or tranexamic acid prior to surgical procedure was given in 19 patients. The post operative period was uneventful in all the patients. 5 patients did not receive any prophylactic treatment for different surgical procedures and no significant post operative bleeding was observed.

Though factor VII deficiency had been described in the literature as a rare disease, we collected and analyzed a large cohort of 56 patients with this disorder in a single medical center. Most of our patients were Sephardic Jews. There had been several reports of excessive bleeding which complicated surgery, especially of the oropharynx and urogenital tract in patients with factor VII deficiency. Levels of 15–25% are recommended for surgery, but the plasma factor VII level required for surgery has been not formally established. We did not find statistically significant differences in factor VII activity levels between the symptomatic patients and the asymptomatic ones (P value<0.36). No life threatening bleeding occurred; only one patient required acute treatment to stop the bleeding. There was no uniform protocol used for prophylactic treatment, which was usually based on “old” drugs such as FFP and tranexamic acid. There was no need for Novoseven. We conclude that treatment guidelines based on the family, personal, surgical history and laboratory results are required for optimal treatment of patients with inherited factor VII deficiency.

No relevant conflicts of interest to declare.