Factor VII Deficiency Clinical Presentation

Updated: Sep 12, 2020
  • Author: Lucas Barreira Angelim, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Presentation

History

Bleeding history is a crucial element in the evaluation of any patient with a hemorrhagic disorder. Of all factors evaluated, clinical history appears to be the best predictor of bleeding risk after hemostatic challenges in inherited factor VII (FVII) deficiencies. [15] This is illustrated by a study  that compared the bleeding score (BS), an assessment tool from the International Society on Thrombosis and Haemostasis (ISTH) based on clinical questions, with Thromboelastography (TEG) and thrombin generation assays (TGAs), which are 2 methods that evaluate global hemostasis. The study showed that BS was compatible with disease severity according to the factor VII activity level (P< 0.05). [16]

In patients with susceptibility to severe bleeds, the first severe bleeds usually occur soon after birth or in infancy; in particular, umbilical cord stump bleeds and muscle or subcutaneous hematomas are associated with a high risk of developing further severe bleeds at a very young age. Life-threatening bleeds, such as intracranial hemorrhage and gastrointestinal bleeds, usually occur before 6 months of age and hemarthrosis usually happens before 5 years of age. [2, 17]

A bleeding disorder is considered likely when a bleeding tendency is discovered in one or more family members or when an abnormal coagulation assay result is obtained as a part of a routine examination or before surgery. [18] Knowing the mode of inheritance of hereditary disorders is important when eliciting the family history. Factor VII deficiency is an autosomal recessive disease, unlike hemophilia, which is an X-linked recessive disease.

Only homozygote or compound heterozygote patients with factor VII deficiency are symptomatic. Heterozygotes who have partial factor VII deficiency may not exhibit hemorrhagic manifestations, even following trauma. In symptomatic patients, clinical phenotypes do not necessarily correlate with factor VII levels. A multicenter European study of patients who are congenitally factor VII deficient showed that clinical symptoms did not vary with the frequency of functional polymorphisms and that homozygotes with the same mutation presented with striking differences in severity of bleeding. [19]

A study done using the European Network of rare bleeding disorders showed that congenital factor VII deficiency was one of the mildest rare factor deficiencies: 54.7% of affected persons were asymptomatic; 16.7% had provoked bleeding with trauma (grade I); 21.7% had spontaneous mild bleeding (grade II); and only 6.9% had spontaneous major bleeding (grade III). In contrast, 48.5% of those with factor XIII deficiency and 42.3% of those with fibrinogen deficiency had spontaneous major bleeding (grade III). The linear regression approach established that the minimum factor VII activity for remaining asymptomatic was 25% and the factor activity associated with spontaneous major bleeding was < 8% [17]

Previously, the severity of the rare bleeding disorders was classified using the same system that is used for hemophilia A and B. However, this classification did not correlate well with clinical phenotypes, so the Rare Blood Disorders (RBD) Working Group conducted a broader review of RBD registries in the UK, the US, and India, as well as of literature, exploring the laboratory–clinical association of RBDs. For factor VII deficiency, the severity, clinical phenotype, and factor VII activity level was as follows [17] :

  • Severe (spontaneous major bleeding likely): < 10%
  • Moderate (mild spontaneous or triggered bleeding): 10%–20%
  • Mild (mostly asymptomatic). > 20%.

Failure to appreciate this classification may put patients at risk.

Patients with factor VII levels of less than 1% frequently present with bleeding symptoms indistinguishable from those of persons with severe hemophilia A or hemophilia B. They may have life-threatening intracerebral hemorrhage manifesting as headaches, seizures, or focal deficits; in particular, Intracranial hemorrhage has been reported in neonates after vaginal delivery. These patients may also experience recurrent hemarthrosis leading to severe arthropathy. 

Patients should be asked about recurrent joint pain, swelling, and motion limitation. Hemarthrosis is sometimes heralded by an aura of mild discomfort that becomes progressively painful over a period of minutes to hours. In children, hemarthrosis usually occurs when the affected child begins to walk.

In patients with mild disease, dental extractions, tonsillectomy, and procedures involving the urogenital tract are frequently associated with bleeding (due to local fibrinolysis), while surgical procedures such as laparotomy, herniorrhaphy, appendectomy, and hysterectomy are not. Postpartum hemorrhage is noted in patients with levels less than 10-20% of the reference range.

In one study, menorrhagia was the most prevalent type of bleeding (46.4% of women), and was the presenting sign in 12% of cases. [20]

Bleeding isolated to a single organ or system (eg, hematuria, hematemesis, hemoptysis) is less likely to be due to a hemostatic abnormality than to a local cause such as neoplasm or ulcer.

A family history is particularly important when a hereditary factor deficiency is considered likely. A specific inquiry should be made about consanguinity. Population genetics information may be helpful; for example, a higher frequency of factor VII deficiency is observed in Iranian and Moroccan Jews.

Drug history is important; drugs of concern may include hepatotoxic drugs, oral anticoagulants (eg, warfarin), and agents such as aspirin. Nutritional history is important to assess the likelihood of vitamin K deficiency. Rarely, drugs such as penicillins and cephalosporins have been associated with acquired isolated factor VII deficiency, but other antibiotics can cause vitamin K deficiency and consequently inhibit the synthesis of functional vitamin K–dependent factors, including factor VII.

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Physical Examination

Physical findings depend on the site and severity of bleeding.

Hemarthrosis may lead to findings of joint swelling, motion limitation, and mild fever. If significant fever develops, infection should be considered. Repeated hemarthrosis leads to joint deformity complicated by muscle atrophy and contractures.

Focal neurological deficits depend on the location of bleeding into the nervous system. Symptoms and signs of subdural hematoma may be delayed for weeks.

Bruising and soft tissue bleeding may be observed with or without trauma. Large hematomas may expand locally and cause compression of adjacent organs, blood vessels, and nerves. Pharyngeal and retropharyngeal hematomas may enlarge and obstruct the airway.

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