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

• Coagulation Factor 5 Deficiency
• Owren’s Disease
• Parahemophilia

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

• Factor V Deficiency is an extremely rare disorder that is caused by the depletion of factor V in blood, which leads to delayed clotting in affected individuals
• Factor V (F V or factor 5) 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
• There are two subtypes of Factor V Deficiency disorder, namely:
  • Inherited Factor V Deficiency is the most common type of Factor V Deficiency, and is caused by mutation(s) in the F5 gene
  • Acquired Factor V Deficiency that arises as a consequence of surgery, a pre-existing condition, child birth or certain treatments; where, the presence of factor V antibody interferes with normal functioning of this coagulation factor
• Factor V Deficiency can either be quantitative (low levels of clotting factor in blood) or qualitative (dysfunctional protein present in normal levels) and may be classified:
  • Type 1, or quantitative Factor V Deficiency, where the levels of factor V are low
  • Type 2, or qualitative Factor V Deficiency, where the levels are normal or near-normal, but the activity of factor V is impaired
• The affected individuals may or may not exhibit symptoms. The levels of factor V in an individual may not correlate with the severity of symptoms, which may include easy bruising and nosebleeds; and in women, heavy bleeding during menstruation
• Administration of frozen plasma is the general treatment method of compensating for factor V shortage. The prognosis is good for most affected individuals. However, in some, bleeding within the brain, lungs, or gastrointestinal tract may be life-threatening

Note: Factor V Deficiency is a completely different disorder from factor V Leiden disorder. The latter is more common than Factor V Deficiency, is characterized by an altered form of factor V, and causes excessive blood clotting.

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

• Factor V Deficiency is an extremely rare disorder, estimated to occur at a frequency of less than 1:1,000,000
• Approximately, only about 200 cases have been reported in the scientific literature
• The condition may be prevalent amongst cultures where marriage is common between close relatives, such as first cousins
• Although the symptoms of Factor V Deficiency can manifest at any age, in those with severe deficiency of this coagulation factor, the symptoms become apparent soon after birth
• Both males and females may be affected by this disorder

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

The risk factors for Factor V Deficiency may include:

• A family history of the condition
• Children of parents who are close blood relatives (such as first cousins) may have an increased risk
• Autoimmune disorders 
• Certain types of cancer
• Childbirth
• Surgeries

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 V Deficiency? (Etiology)

Inherited Factor V Deficiency is caused by mutations in the F5 gene.

• The F5 gene codes for coagulation factor V, which is a large glycoprotein
• This protein acts as a catalyst for the initial step in clotting, which is the conversion of prothrombin to thrombin
• This crucial step in the clotting process also forms the convergence point between intrinsic and extrinsic clotting pathways
• When the F5 gene is mutated, F5 protein levels are depleted leading to the manifestation of symptoms
• Factor V Deficiency is inherited in an autosomal recessive manner. In this type of inheritance, an individual must possess both copies of the causative F5 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 of the disorder
  • In the case of Factor V Deficiency, even those with a single copy of the defective gene may exhibit minor or moderate symptoms
  • Those with two defective copies of the F5 gene may exhibit severe symptoms soon after birth

Acquired Factor V Deficiency may be caused by antibodies that bind to factor V. These anti-factor V antibodies may be generated by: 

• Certain autoimmune disorders, in which the antibodies attack an individual’s healthy cells
• Bovine thrombin used during surgeries
• Treatment with fibrin glue such as for fistulas
• Certain cancers and their treatments
• During or immediately after child delivery

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 V, which catalyze crucial reactions, are central to the action of these pathways. Each factor activates the next in a stepwise manner
• Factor V is active in the common clotting pathway. It assists in the conversion of prothrombin to thrombin

What are the Signs and Symptoms of Factor V Deficiency?

The signs and symptoms of Factor V Deficiency may vary in age at presentation, as well as in their type and severity. The following are some known signs and symptoms of Factor V Deficiency:

• Frequent and easy bruising
• Subcutaneous bleeding (bleeding under the skin)
• Nosebleeds
• Bleeding from the gum
• Bleeding in the mouth, particularly following dental procedures
• Heavy and prolonged menstrual bleeding in women

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 lungs, causing:
  • Difficulty breathing
  • Cough, which may contain blood
• Bleeding in the joints (hemarthrosis), which may cause the following:
  • Swelling
  • Stiffness and pain
  • Tingling sensation
  • The joint may feel warm to touch
• Bleeding into the brain, which may cause
  • Headaches
  • Seizures
  • Numbness 
  • Nausea and vomiting
  • Vision changes
  • Confusion

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

How is Factor V Deficiency Diagnosed?

The diagnosis of Factor V 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 
  • Thrombin clotting time (TCT) test
  • Factor V levels (deficiency of the combined factors V and VIII is a separate disorder)
  • Assay factor V activity
• Inhibitor tests to check for immune system suppression of blood clotting factors
• 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 V 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 V Deficiency?

The following are some potential complications of Factor V Deficiency:

• Increased incidence of brain stroke 
• Clot formation in the lung
• Deep vein thrombosis
• Treatment complication: Generation of anti-factor V alloantibodies as a consequence of Factor V Deficiency treatment

How is Factor V Deficiency Treated?

Treatment options for Factor V Deficiency are specific to the affected individual; it is determined on a case-by-case basis. The treatment methods may include the following:

• Fresh frozen plasma to replenish factor V, typically required in those with severe symptoms, or just before surgery 
• Platelets transfusions 
• 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

How can Factor V Deficiency be Prevented?

Inherited Factor V Deficiency is the most common type of Factor V Deficiency; presently, there are no methods or guidelines available for the prevention of this blood disorder.

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

The acquired form of Factor V Deficiency can be addressed through proper treatment of the causative (pre-existing) condition.

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

The prognosis of Factor V Deficiency depends on the severity of the signs and symptoms, the individual’s overall health, and his/her response to treatment.

• Generally, the affected individuals are able manage the condition and live normal lives
• However, if an individual presents with bleeding of the gastrointestinal tract, lungs, or the brain, the prognosis may be guarded
• Additionally, if Factor V Deficiency occurs secondary to a pre-existing condition (acquired), then the outcome may be determined by the severity of the underlying condition

Additional and Relevant Useful information for Factor V Deficiency:

The following are some additional synonyms for Factor V Deficiency:

• Autoprothrombin 1 Deficiency
• F V Deficiency
• F5 Deficiency
• Factor 5 Deficiency
• Labile Factor Deficiency
• Owren Disease
• Proaccelerin Deficiency

Factor V Deficiency was first reported from Norway by Dr. Paul Owren in the year 1947.