Factor V deficiency: a very rare inherited bleeding disorder

Normal clotting relies on a series of proteins called coagulation factors, each numbered with Roman numerals from I to XIII, being activated in order. GOSH explains that if any one factor is missing the chain of reactions does not happen as it should, and blood loss can be severe and life-threatening. In factor V deficiency the missing or reduced protein is factor V.

The name is easily confused with factor V Leiden, which is a common inherited tendency to form clots. GOSH is explicit that factor V deficiency is a completely different condition, and that the combination of factor V and factor VIII deficiency is also a separate condition. Guy's and St Thomas' NHS Foundation Trust lists both single factor V deficiency and combined factor V and VIII deficiency under rare bleeding disorders.

The Haemophilia Society says around one in 2,000 people in the UK have a diagnosed bleeding disorder, almost always inherited, and that the most common are von Willebrand disorder and haemophilia A. Factor V deficiency sits among the rare disorders that make up the remainder.

GOSH says factor V deficiency is caused by a variant, or change, on the F5 gene, inherited in an autosomal recessive manner. A person has to inherit the faulty gene from both parents to develop the severe form. For two carrier parents each pregnancy carries a 75 per cent chance of an unaffected child and a 25 per cent chance of an affected child. GOSH adds that recessive disorders are more common in parts of the world where marriage between close relatives is common.

People who carry one copy are carriers. The majority are healthy, but GOSH says occasionally affected carriers may show mild symptoms that may or may not need treatment. The Haemophilia Society notes that as many as a third of bleeding disorder diagnoses have no known family history and can result from a random gene mutation.

GOSH says that if the level of factor V is low or absent, or it does not work properly, symptoms may be present, often early in life. These can include bleeding in the brain, bleeding from the umbilical cord around birth, nosebleeds and bruising. Mouth bleeds after dental work can occur, as can blood loss during childbirth and heavy menstrual periods. Occasionally bleeding can occur inside the body.

Guy's and St Thomas' adds that mild forms usually do not cause everyday bleeding problems, that people are often diagnosed later in life, for example after unexpected heavy bleeding during surgery or dental extractions, and that affected women can suffer heavy periods or excessive bleeding with childbirth.

GOSH says suspicion may arise because of bruising or bleeding, or during routine checks before an operation or after an injury. A blood sample is tested in a laboratory. A test measuring how long a sample takes to clot may suggest a clotting disorder, which is then investigated further. The level of factor V is checked along with factor VIII, because the two sometimes occur together and give a different pattern of bleeding. Doctors try to identify the gene variant, which helps with planning for future siblings and testing other family members, and scans such as MRI, CT or ultrasound may be used to find internal bleeds such as inside a joint.

With a family history, GOSH says factor V deficiency can be diagnosed before birth using chorionic villus sampling early in pregnancy or amniocentesis around 15 to 20 weeks.

GOSH says that for mildly affected children whose symptoms are not problematic, regular treatment may not be needed and treatment is given on demand as symptoms occur. Children with severe deficiency need regular preventative (prophylaxis) treatment to prevent severe bleeding, and treatment may be required for planned operations or injuries.

Because factor V is not available as a separate replacement, an infusion of fresh frozen plasma is usually given. For minor symptoms the medicine tranexamic acid can be given by mouth, into a vein or applied to the skin, to help stabilise blood clots. GOSH says females may need additional measures to make periods manageable, such as tranexamic acid before and during periods or hormonal methods such as the contraceptive pill.

Guy's and St Thomas' notes that in all rare bleeding disorders tranexamic acid can help minimise bleeding and that treatment is usually only needed occasionally, for troublesome bleeding or to prevent excessive bleeding with surgery, invasive procedures, dental work or childbirth.

GOSH says children and young people with mild factor V deficiency have a normal life span. Contact sports with a high risk of head injury may need to be avoided, but most day-to-day activities cause few problems. It advises wearing a medical alert necklace or bracelet and planning any surgery or pregnancy carefully, with all healthcare professionals aware.

Care includes regular review at a specialist centre, with injections given with some care: immunisations should be given under the skin rather than into a muscle to reduce the risk of a painful bruised swelling. GOSH says that lifelong monitoring and treatment are needed, that there is a planned transition to adult services as children grow, and that genetic counselling is available to affected people and unaffected carriers before planning a family.

Rare bleeding disorders are looked after in NHS haemophilia centres. If you have unexplained heavy bleeding, a GP can arrange initial blood tests and refer you to haematology. Private haematology can provide assessment, but products such as plasma and ongoing monitoring depend on a specialist centre, so most people are followed by an NHS haemophilia team. The Haemophilia Society is a source of information and peer support.