What are the other Names for this Condition? (Also Known as/Synonyms)

• Alexander’s Disease
• Proconvertin Deficiency
• Serum Prothrombin Conversion Accelerator Deficiency

What is Factor VII Deficiency? (Definition/Background Information)

• Factor VII Deficiency is a bleeding disorder, caused by the deficiency of coagulation factor VII. It is considered the most common type of “rare bleeding disorders”
• Factor VII (F VII or factor 7) is one of the 12 clotting factors that are labeled factors I to XIII (factors V and VI actually denote the same clotting factor)
• Clotting factors are proteins that help form blood clots at the site of a blood vessel injury. A blood clot stops further blood loss and allows the blood vessel to continue functioning
• The deficiency of factor VII leads to delayed clotting in affected individuals. There are two subtypes of this disorder, namely:
  • Inherited Factor VII Deficiency, caused by mutation(s) in the F7 gene
  • Acquired Factor VII Deficiency caused by liver disease, vitamin K deficiency, or from anticoagulant drugs
• The severity of the condition varies from individual to individual, and can range from an absence of symptoms to even life-threatening complications
• Factor VII Deficiency can be treated with intravenous concentrates of factor VII, which result in good outcomes. However, the prognosis may be guarded, if complications, such as severe internal bleeding, develop

Who gets Factor VII Deficiency? (Age and Sex Distribution)

• Factor VII Deficiency is very rare, occurring at frequencies between 1:300,000 to 1:500,000 births. However, it is believed that many cases of Factor VII Deficiency remain undiagnosed or misdiagnosed
• Factor VII Deficiency affects all ages; the age of onset of symptoms vary and can range from childhood to adulthood
• Both males and females are affected by the disorder
• The disorder is reported to occur without any racial or ethnic bias

What are the Risk Factors for Factor VII Deficiency? (Predisposing Factors)

The risk factors associated with Factor VII Deficiency may include:

• A family history of the condition
• Children of parents who are close blood relatives (such as first cousins or uncle and niece) may have an increased risk
• Liver disease
• Vitamin K deficiency
• Excess intake of antibiotics
• Administration of blood thinners (anticoagulants) such as coumadin

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Factor VII Deficiency? (Etiology)

Inherited Factor VII Deficiency is caused by mutations in the F7 gene.

• The F7 gene codes for coagulation factor V, a protein that plays a crucial role in the extrinsic clotting pathway
• The protein, also known as proconvertin, binds to factor 3 protein (tissue factor) to initiate the clotting mechanism
• When the F7 gene is mutated, the F7 protein levels are depleted, leading to a manifestation of symptoms
• Factor VII Deficiency is inherited in an autosomal recessive manner. In this type of inheritance, an individual must possess both copies of the causative F7 gene in the defective form in each of his/her body’s cells for the disorder to occur. An affected individual inherits a single defective copy of the gene from each parent. Typically, parents are unaffected by the disorder and are known as “carriers”

Acquired Factor VII Deficiency may be caused by the following conditions/factors:

• Liver disease, since liver is the site of factor VII production
• Vitamin K deficiency: Vitamin K helps in keeping clotting factors at optimum levels in the body
• Use of blood thinners, which can interfere with blood clotting

The following is the sequence of events that lead to blood clotting:

• The clotting process starts with injury to a blood vessel, which causes it to constrict. Called the vascular phase, this is the first reaction of a blood vessel to damage. Constriction of a blood vessel reduces the flow of blood to the site of injury, which minimizes blood loss
• Next, the circulating platelets clump along the site of blood vessel injury. The platelets form a foundation for a blood clot and release chemicals that stimulate clotting
• The coagulation phase then causes a blood clot to form. Clotting occurs when an enzyme, called thrombin, converts a soluble protein fibrinogen, into its insoluble form, fibrin. Fibrin proteins make up the bulk of a blood clot
• Thrombin is activated by the merging of two pathways, called the intrinsic and extrinsic pathways, into the common pathway. These are initiated by different parts of the body after blood vessel damage:
  • The intrinsic pathway begins in blood with the activation of circulating proteins
  • The extrinsic pathway begins in the blood vessel with the release of protein factors by damaged cells lining the vessel
• The extrinsic pathway is the first to activate. The intrinsic pathway then reinforces the extrinsic pathway and provides longer-lasting clotting effects
• Coagulation factors such as factor VII, which are part of crucial reactions that begin the clotting process, are central to the action of these pathways. Each factor activates the next in a stepwise manner

What are the Signs and Symptoms of Factor VII Deficiency?

The signs and symptoms of Factor VII Deficiency may vary from mild to severe. Typically, the lesser the amount of F7 protein present in blood, the more severe is the symptoms.

The signs and symptoms may include:

• Bleeding from the umbilical stump in newborns (soon after birth)
• Frequent and easy bruising
• Subcutaneous bleeding (bleeding under the skin)
• Bleeding for a long time after a cut, such as after a circumcision 
• Nosebleeds
• Bleeding from the gums
• Bleeding in the mouth, particularly following dental procedures
• Heavy bleeding after an injury
• Abnormal bleeding during or after (minor) surgery
• Heavy and prolonged menstrual bleeding in women
• Heavy bleeding during childbirth in women
• Blood in urine (in rare cases)

In addition to the above, in severe cases, the following signs and symptoms may occur:

• Bleeding in the gastrointestinal tract, causing:
  • Abdominal pain
  • Black, tarry stools
  • Weakness
  • Lightheadedness
• Bleeding in the muscles, causing:
  • Severe pain
  • Difficulty in moving the affected muscle tissue
  • Loss of sensation in the affected area
• Bleeding in the joints (hemarthrosis), which may cause the following:
  • Swelling
  • Stiffness and pain
  • Tingling sensation
  • The joint may feel warm to touch
• Bleeding in the central nervous system, including the spinal cord and brain, which may cause:
  • Headaches
  • Seizures
  • Numbness 
  • Nausea and vomiting
  • Vision changes
  • Confusion

In cases with Acquired Factor VII Deficiency, the signs and symptoms may include those of the pre-existing condition that caused Factor VII Deficiency.

How is Factor VII Deficiency Diagnosed?

The diagnosis of Factor VII Deficiency is made on the basis of the following tools:

• A complete physical examination
• Assessment of signs and symptoms
• Evaluation of one’s personal and family medical history
• Blood tests to measure time taken for clot formation, which include:
  • Serum prothrombin or PT time test
  • Partial thromboplastin time (PTT) test
  • Factor VII levels
  • Assay factor VII activity
• Liver function test
• Imaging tests to check for internal bleeding of the gastrointestinal tract, lungs, or brain:
  • Ultrasound imaging of the affected region
  • Computed tomography and/or magnetic resonance imaging (MRI) of the affected region
  • In addition, if Factor VII Deficiency is acquired, relevant tests pertaining to pre-existing conditions may be necessary

Note:

Certain medications that one is currently taking may influence the outcome of the lab tests. Hence, it is important to inform the healthcare provider of the complete list of medications (including any herbal supplements) one is taking. This will help the healthcare provider interpret the test results more accurately and avoid unnecessary chances of a misdiagnosis.

The laboratory test results are NOT to be interpreted as results of a “stand-alone” test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. The healthcare providers will explain the meaning of the test results, based on the overall clinical scenario.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Factor VII Deficiency?

Factor VII Deficiency complications may include:

• Anemia from excessive bleeding
• Problems with movement owing to pain in the muscles and joints
• Increased incidence of brain stroke 
• Deep vein thrombosis

How is Factor VII Deficiency Treated?

The treatment methods for Factor VII Deficiency are specific to an individual. It is also based on the cause and severity of the presenting symptoms. In some cases, prophylactic treatment may be necessary, in order to prevent bleeding in the brain.

The treatment options may include:

• Frozen plasma
• Factor VII concentrate
• Prothrombin complex concentrate rich in factor VII
• Recombinant factor VII concentrate
• In women, the following methods may be adopted to avoid excessive bleeding during menstruation:
  • Use of intra-uterine contraceptive devices 
  • Contraceptive pills for controlling bleeding
  • Antifibrinolytic drugs, such as aminocaproic acid
• Vitamin K supplements, for vitamin K deficiency causing acquired Factor VII Deficiency
• Medications and/or surgery for liver dysfunction and consequent acquired Factor VII Deficiency, based upon the individual’s specific health condition
• Discontinuing blood-thinning medications

How is Factor VII Deficiency Prevented?

Inherited Factor VII Deficiency is the most common type of Factor VII Deficiency, and presently, there are no methods or guidelines available for the prevention of this condition.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited genetic disorders such as Factor VII Deficiency
• The acquired form of Factor VII Deficiency can be addressed through proper treatment of the causative (pre-existing) condition 
• Avoiding blood thinners known to cause this bleeding disorder may help prevent severe bleeding symptoms

Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended in individuals who have been diagnosed with Factor VII Deficiency.

What is the Prognosis of Factor VII Deficiency? (Outcomes/Resolutions)

The prognosis of Factor VII Deficiency is determined by whether the condition is genetic or acquired, the severity of the symptoms, age of manifestation of the disorder, the overall health of an affected individual, and his/her response to treatment.

• With an early diagnosis and prompt treatment, individuals with inherited Factor VII Deficiency may have good outcomes
• However, complications, such as bleeding in the gastrointestinal tract and brain, may be life-threatening
• Additionally, if Factor VII Deficiency occurs secondary to a pre-existing condition (acquired), then the outcome may be determined by the severity of the underlying disorder

Additional and Relevant Useful Information for Factor VII Deficiency:

The following are some additional synonyms for Factor VII Deficiency:

• F VII Deficiency
• F7 Deficiency
• Factor 7 Deficiency
• Hemophilia due to Factor VII Deficiency
• Hypoproconvertinemia
• Prothrombin Conversion Accelerator Deficiency

Dr. Alexander and fellow-scientists described Factor VII Deficiency in the medical literature for the first time in 1951. At the time, it was termed “Prothrombin Conversion Accelerator Deficiency”. The term Factor VII Deficiency is synonymously termed Alexander’s Disease after Dr. Alexander.