The clinical presentation of the disease is variable [3] [11]. Patients with a mild-to-moderate disease may exhibit chronic epistaxis, gingival bleeding. Women are likely to experience menorrhagia and consequently develop iron deficiency anemia. The featured mucosal bleeding is reminiscent of platelet function disorders. Severe forms of FVII deficiency are characterized by life-threatening manifestations such as intracranial hemorrhage. Moreover, CNS hemorrhage can occur in up to 60% of cases [3] [11], especially in newborns after birth.

Hemarthrosis can also develop in patients with FVII deficiency [3] [11] although it is uncommon. This is a consistent finding in hemophilia and can lead to destruction and degeneration of joints in both diseases [12]. Other signs of bleeding include hematuria, melena, or hematochezia.

Physical exam

Bruising may be apparent on examination. Also, a limited range of joint motion is notable in patients with joint bleeding.

Very importantly, the clinician should be vigilant about signs of deep vein thrombosis (DVT) and neural deficits.

Patients with abnormal bleeding should be evaluated with a thorough personal and family history as well as a review of any medication intake. The assessment also includes a complete physical exam and the appropriate studies.

Laboratory tests

The diagnostic tools include a complete blood count (CBC) and a coagulation panel. The typical findings include a prolonged PT with a normal aPTT. A further study is conducted using a mixture of normal plasma and the patient's plasma to repeat testing for PT. This is to rule out the presence of an FVII inhibitor.

An assay for FVII determines the activity of this clotting factor and confirms the disease. Additionally, a radioimmunoassay test may be used to measure FVII antigen. Finally, affected families can undergo genetic testing for identification of the specific mutant genes.

The treatment of patients with FVII deficiency depends on factors such as the clinical phenotype, age, comorbidities (if present), and patient's preference. The care is best delivered by a team of a pediatrician or general physician, hematologist, genetic counselor, and other specialists as needed.

Blood replacement should be considered based on the severity of the patient's disease. FFP is utilized in developing areas but has the disadvantage since it increases blood volume and carries a rare risk of transmission of infection. FFP may be beneficial in the context of secondary prophylaxis.

Various preparations can be used in patients with FVII deficiency. Recombinant FVIIa is the optimal choice as a synthetic supply of the deficient clotting factor [13]. Another option is the pdFVII concentrate, which is accompanied by prothrombin complex concentrates. Both recombinant FVIIa and pdFVII concentrates are effective for treatment of active bleeding and prophylaxis. Since these products exhibit a short half-life, they are prescribed for multiple times daily (if possible) and may be administered at home.

Prevention of bleeding episodes is paramount, especially in children. Additionally, prophylaxis should be highly considered for patients with severe FVII deficiency undergoing surgery. One main drawback of replacement therapy is its risk for complications such as thrombosis [14].

Special considerations

Since menorrhagia is prevalent in women with FVII deficiency, they may require treatment and replacement therapy during a partial duration of the menstrual cycle. Furthermore, women undergoing childbirth may need replacement management [15]. Finally, iron deficiency anemia in women should be treated accordingly.

The majority of patients with the severe forms of FVII deficiency are diagnosed early in life, especially in infancy. Approximately 60% to 70% of hemorrhagic cases emerge from bleeding in the CNS or gastrointestinal (GI) tract [8] [9].

Patients with serious bleeding are at risk for mortality. One of the leading causes of death is an intracerebral hemorrhage. Additionally, thrombosis is a complication of FVII deficiency [10]

This coagulation disorder is the result of mutations in the F7 gene, which encodes FVII. More than 100 mutations, especially of the missense type, have been reported [2] [3]. Genetic defects influence the levels of this clotting factor. The deficiency can arise from reduced synthesis or dysfunction of FVII.

Acquired FVII deficiency, which is more common than the inherited form of the disease, is attributed to factors that cause vitamin K [4]. Examples include vitamin K deficiency, liver disease, or drugs that affect this vitamin such as oral anticoagulants, penicillin, and cephalosporins.

The prevalence of FVII deficiency is 1 per population of 500,000. The patient demographics reveals no gender or age preference. While this disease does not have a predilection for racial or ethnic background, certain populations such as Moroccan and Iranian Jews possess mutations that predispose them to this disease. Specifically, the missense Ala244Val mutation is responsible for the deficiency. Additionally, there are polymorphisms that have been observed in specific groups. For example, the sequence involving the Arg353Gln substitution is more frequently present in Gujaratis and Dravidian Indians [5]. Additionally, geographical regions with higher prevalence of consanguinity have a greater occurrence of this disease.

The pathogenesis of FVII deficiency arises from genetic mutations in the F7 gene located on chromosome 13. This bleeding disorder may also be acquired.

Inherited

Studies have investigated the underlying mechanisms responsible for specific phenotypes. It remains a challenge to establish a relationship between certain mutations and the effects [6]. One study identified 19 distinct mutations, of which 12 were previously undiscovered. The majority were missense defects of the serine protease domain and almost half were homozygous. Molecular analysis of FVIIa and the FVIIa–tissue factor complex suggested that the genetic mutations resulted in the dysfunction of the catalytic portion [6].

Acquired

This type of deficiency most frequently results from the effects of vitamin K antagonists and liver disease. Warfarin is an example of the former, as it is an inhibitor of vitamin K-dependent enzymes. Furthermore, liver pathologies such as Dubin-Johnson syndrome and Gilbert's syndrome exhibit reduced FVII concentration [7]. Additionally, acquired FVII can emerge from disorders such as myeloma, aplastic anemia and conditions such as sepsis.

Patients are advised to exercise caution with physical activities by avoiding contact sports, selecting safer sports, and engaging in regimens that strengthen the muscles and joints.

Additionally, parents and children should learn about the disease, how to treat it, and when to seek emergency care. Affected individuals should wear a medical alert bracelet or carry documents in case of emergency or trauma.

Genetic counseling is offered to patients and family members in order to provide them with information about the disease, its mode of inheritance, expectations, and other important details.

Factor VII (FVII) deficiency is an autosomal recessive hemorrhagic disorder arising from a mutation in the F7 gene, which codes for clotting factor VII (FVII). This rare condition is the most prevalent coagulation disorder. FVII plays a key role in hemostasis and clot formation. Hence, an insufficiency or impairment of this clotting factor leads to abnormal bleeding in homozygotes and compound heterozygotes while heterozygotes are asymptomatic. This disease can also be acquired from the effects of medications or liver disease on vitamin K, which is essential for the production of FVII.

The clinical presentation of FVII deficiency is variable. Furthermore, the severity of this disease does not correlate with the levels of FVII [1]. Mild disease is characterized by mucosal hemorrhages such as epistaxis and menorrhagia or bleeding in response to surgical procedures. Severe disease is associated with mortality since it typically manifests in early infancy and causes intracerebral bleeding.

Patients with abnormal bleeding patterns should be assessed with a detailed account of the personal and family history, a physical exam, and laboratory tests. The latter includes coagulation studies and specific assays for confirmation of the diagnosis. The results that are consistent with this disease include a normal activated partial thromboplastin time (aPTT) and a prolonged prothrombin time (PT).

The management of these patients consists of treatment and prophylaxis. The medical team will take into account the patient's symptomology, age, coexisting diseases and other factors while carefully weighing the benefits and the drawbacks of each blood preparation. Blood replacement products such as fresh frozen plasma (FFP), recombinant FVIIa and plasma-derived FVII (pdFVII) can be used for patients with active bleeding and may be administered in the perioperative setting as well.

Since this disease has a high risk of mortality in a subset of patients, early diagnosis and treatment are essential. Parents and affected children should receive education about the disease, how to treat it, and understand the precautions.

What is Factor VII deficiency?

This is an inherited bleeding disease that results from decreased or impaired activity of clotting factor VII. The body makes numerous clotting factors which are very important for proper clot formation. Therefore, if clotting factor VII is not normal, then patients will have prolonged and abnormal bleeding.

What are the causes?

Factor VII deficiency is caused by mutations in the F7 gene, which produces clotting factor VII. This disease may also be acquired from certain medications such as warfarin or even certain liver diseases.

This disease is inherited in an autosomal recessive pattern. To be affected with this disease, the patient will inherit a bad copy from each parent. This means that each parent is a carrier of the disease.

What are the signs and symptoms?

The symptoms vary as some patients experience no symptoms, some may have mild symptoms, and others may have serious complications. The features may include:

• Nosebleeds
• Bleeding from the gums
• Bruising easily
• Long and heavy menstrual period in women
• Bleeding in the brain
• Bleeding into the joints, which causes damage to the joints and limited range of movement
• Blood in urine
• Bloody stools

How is it diagnosed?

When an individual presents with abnormal bleeding patterns, the clinician will obtain the patient and family history, perform a physical exam, and order the following tests:

• Complete blood count (CBC)
• Clotting tests such as activated partial thromboplastin time (aPTT) and prothrombin time (PT): these patients will a normal aPTT and a prolonged PT
• Specialized tests known as assays are also performed to confirm the diagnosis

How is it treated?

Treatment and preventative therapy depend on the severity of the disease, the symptoms, the age of the patient, other health problems in the patient, and the patient's wishes. Treatment options include blood products such as:

• Recombinant factor VIIa (rFVIIa): this a synthetic form of factor VII
• Prothrombin complex concentrates (PCCs)
• Fresh frozen plasma (FFP)

Generally, these medications can increase the risk of developing blood clots. Therefore, doctors and patients should discuss the pros and cons of these medications.

Patients undergoing surgery may need prophylactic (preventative) medicine. Women with heavy periods due to this disease may also require special treatment.

Can it be prevented?

The disease is inherited and cannot be prevented. However, genetic counseling is offered to affected individuals and their family members to provide them with education about the disease, how it is inherited, how it is treated, and other specific details.

Patients are advised to:

• Avoid contact sports
• Choose safer sports
• Participate in activities that strengthen muscles and joints

Also, parents and children should learn about the disease, how to treat it, and know when to seek emergency care. Patients should wear a medical alert bracelet or carry medical documents in case of emergency or trauma.

What is the prognosis?

Severe bleeding is associated with a high risk for death. Therefore, early diagnosis and treatment are important, especially in affected infants.

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