Factor X deficiency

• Factor X deficiency is a coagulation (clotting) disorder that occurs when an individual has too little factor X, a clotting protein that plays a key role in the coagulation cascade, which is triggered when a blood vessel is damaged. Factor X is also sometimes referred to as the Stuart-Prower factor after the first patients diagnosed with the disorder, or thrombokinase. Factor X is synthesized in the liver in a process that requires vitamin K.
• Factor X deficiency is the rarest of all coagulation disorders. These disorders occur when the blood does not form clots properly. Blood clots are clumps of different types of blood cells and clotting factors that stop bleeding after an injury. The process of blood clotting is called coagulation or hemostasis. Factor X plays a crucial role in the coagulation cascade because it is the first enzyme in the pathway of clot or thrombus formation.
• When a blood vessel (vein or artery) becomes injured, it narrows to slow blood flow so that clotting can begin. At the same time, the blood that has leaked outside of the injured blood vessel presses against the vessel to help prevent further blood loss. Blood cells called platelets are activated to move toward the site of injury. Once platelets reach the site of injury, a series of reactions by enzymes called coagulation factors lead to the activation of a protein called thrombin. This protein converts a blood clotting factor, fibrinogen, into long strands that form a net around the platelets and blood cells. This net helps trap more platelets to form a blood clot.
• The blood clot, also called a thrombus, is a temporary plug to control bleeding. Once the platelets are clumped together, they become activated and stick together. Sometimes blood clots are visible and appear as bruises under the skin or scabs on the skin. Once the blood vessel is healed, other blood factors are released to destroy the clot, which is then dissolved into the blood.
• Factor X deficiency can occur at any age, although the most severe forms are evident in infancy. Because of an inability to properly form clots, patients experience prolonged bleeding in response to injuries such as scrapes and cuts or nosebleeds. Patients may experience excessive bleeding after undergoing surgical or dental procedures and may also be more susceptible to bruising. People with factor X deficiency who sustain an injury may be at risk of bleeding to death.
• Treatment of factor X deficiency involves replacement of factor X using either fresh frozen plasma or prothrombin complex concentrate. Both of these treatments contain factor X and other clotting factors.
• Factor X deficiency is caused by a mutation in the F10 gene, which provides instructions for making the factor X protein. The gene for factor X is found on chromosome 13. More than 13 different mutations have been found in the factor X gene that cause factor X deficiency, and the disease is caused by different mutations in different people. Factor X deficiency is usually inherited as an autosomal recessive trait, meaning an individual must inherit two defective copies of the causative gene, one copy from each parent, for the disease to appear.
• Some people with factor X deficiency do not have a family history of the disorder. In these cases, the disease is acquired, or caused by environmental factors. Acquired factor X deficiency can be caused by having low levels of vitamin K or by using some blood thinning medications, such as warfarin, that cause the body to produce an inactive form of factor X. Diseases associated with factor X deficiency include severe liver disease, amyloidosis (a disease in which proteins are deposited in organs or tissues), and certain cancers, such as leukemia and melanoma.
• Factor X deficiency does not occur with greater frequency in any one part of the world. Men and women are affected in equal numbers. This disorder affects approximately one out of 1,000,000 people. There is a greater risk of the disease occurring if close relatives intermarry.

• General: Factor X deficiency is an extremely rare bleeding disorder that is usually inherited or passed down in families. In some cases, however, there is no family history of the disorder and the condition is the result of a spontaneous or random gene mutation.
• Factor X deficiency does not occur with greater frequency in any one part of the world. Men and women are affected in equal numbers. Factor X deficiency can occur at any age, although the most severe forms are evident in infancy. This disorder affects approximately one out of 1,000,000 people. There is a greater risk of the disease occurring if close relatives intermarry.
• Inheritance: Factor X deficiency is caused by a mutation in the F10 gene, which provides instructions for making the factor X protein. The gene for factor X is found on chromosome 13. The disease is caused by different mutations in different people. More than 13 different mutations have been found in the factor X gene that cause factor X deficiency.
• Genes are inherited on alleles, or genetic variants of a specific gene. Individuals receive two copies of most genes, one from the mother and one from the father. Because factor X deficiency is an autosomal recessive disorder, an individual must inherit two mutated alleles for the disease to appear. People who have only one mutated allele do not experience symptoms but are called carriers because they can pass the mutated gene to their children. If one parent is a carrier, there is a 50% chance with each birth that the child will also be a carrier, and a 0% chance that the child will inherit the disease. If both parents are carriers, there is a 25% chance with each birth that the child will inherit the disease, a 50% chance that each child will be a carrier, and a 25% chance that each child will not inherit either mutated allele.
• Medical conditions: Factor X deficiency has been linked to a number of other medical conditions. Factor X deficiency occurs in approximately 8% of patients with amyloidosis, a disease in which proteins build up in tissues and organs. Other diseases associated with factor X deficiency include severe liver disease, myeloma, leukemia, pneumonia, upper respiratory tract infection, and leprosy. The relationship between these diseases and factor X deficiency is under investigation.

• Genetic mutations: Patients with factor X deficiency have mutations in the gene that provides instructions for making the clotting factor X. Factor X deficiency is caused by a mutation in the F10 gene, which provides instructions for making the factor X protein. The gene for factor X is found on chromosome 13. The disease is caused by different mutations in different people. More than 13 different mutations that cause factor X deficiency have been found in the factor X gene. Factor X deficiency makes affected individuals unable to properly form blood clots. Blood clots are clumps of different types of blood cells and clotting factors that stop bleeding after an injury. The process of blood clotting is called coagulation or hemostasis. Factor X is synthesized in the liver in a process that requires vitamin K. Factor X plays a crucial role in the coagulation cascade because it is the first enzyme in the pathway of thrombus or clot formation.
• Although factor X deficiency is usually inherited, it can occur in individuals who have no family history of the disorder. In these cases, the disease is acquired or caused by a spontaneous genetic mutation. Acquired factor X deficiency may be caused by low levels of vitamin K or use of some blood thinning medications, such as warfarin, that cause the body to produce an inactive form of factor X.
• Inheritance: Factor X deficiency is usually inherited or passed down in families as an autosomal recessive trait. Different mutations that cause the production of abnormal levels of factor X protein are being studied. Depending on the type of mutation, the disease can range from mild to severe.
• Genes are inherited on alleles, which are genetic variants of a specific gene. Each person gets one allele from their mother and one from their father. To inherit factor X deficiency, an individual must inherit two mutated alleles of a single gene. People who have only one mutated allele do not experience symptoms but are called carriers because they can pass the mutated gene to their children. If one parent is a carrier, there is a 50% chance with each birth that the child will also be a carrier, and a 0% chance that the child will inherit the disease. If both parents are carriers, there is a 25% chance with each birth that the child will inherit the disease, a 50% chance that each child will be a carrier, and a 25% chance that each child will not inherit either mutated allele.
• Medical conditions: Factor X deficiency has been associated with a number of other medical conditions. Factor X deficiency occurs in approximately 8% of patients with amyloidosis, a disease caused by an abnormal buildup of proteins in tissues and organs. Other diseases associated with factor X deficiency include severe liver disease, myeloma, leukemia, neoplasm (tumor), pneumonia infection, upper respiratory tract infection, and leprosy. The relationship between these diseases and factor X deficiency is under investigation.
• Other: Acquired factor X deficiency may be linked to using lupus anticoagulant (antibodies that prevent clotting), sodium valproate (an anticonvulsant used to treat seizures), or thrombin inhibitor. It has also been suggested that acquired factor X deficiency may be caused by severe burns.

• General: Because of an inability to properly form clots, patients with factor X deficiency experience prolonged bleeding in response to injuries such as scrapes and cuts or nosebleeds. Patients may also experience excessive bleeding after undergoing surgical or dental procedures and may be more susceptible to bruising. Factor X deficiency can occur at any age, although the most severe forms are evident in infancy. Injuries that result in any type of bleeding may become life-threatening.
• Generally, the lower the factor X level, the more serious the symptoms. The severity of symptoms may vary, with some patients experiencing more difficulty in forming clots than others. In patients who have mild factor X deficiency (10% or more of normal factor X activity), prolonged bleeding may result only after very severe injuries or surgery, and which may not occur until adulthood. Patients with severe factor X deficiency have less than 1% of normal levels of factor X. These individuals may take days or weeks to heal from even a minor injury.
• Hemorrhage: Hemorrhaging or uncontrolled bleeding is the hallmark of factor X deficiency. Hemorrhaging may occur in infants when the umbilical cord is cut or when undergoing circumcision. Additional bleeding episodes occur when the infant becomes mobile. Internal bleeding, which may or may not cause any specific symptoms, may occur anywhere in the body and may lead to organ damage or even death. Bleeding into joints, muscles, and mucus membranes is common and may cause the joints to swell and become painful. Spontaneous bleeding and gastrointestinal tract and urinary tract hemorrhaging may occur. Some patients have blood in their urine (hematuria) or stool (hematochezia), which is often the result of internal bleeding from an organ, such as the kidney, bladder, intestines, or stomach. Females may experience longer and heavier bleeding during the menstrual period and are susceptible to first trimester miscarriage. A mother with factor X deficiency may hemorrhage after giving birth.
• Other: Tiny red dots, called petechiae, may occur if there is bleeding under the skin. This condition is called purpura.

• General: If factor X deficiency is suspected because of uncontrolled bleeding or a family history, a doctor will take a detailed medical history and perform a thorough physical examination. It is important for patients to tell their doctor if they are trying a new diet or taking any new prescription or over-the-counter drugs, herbs, or supplements (e.g., aspirin or related medicines, nonsteroidal anti-inflammatory drugs, or vitamin K) because they may cause the disorder or worsen its symptoms.
• In cases of acquired factor X deficiency, the physical examination may reveal signs of underlying disease, including liver disease, intestinal malabsorption, upper respiratory tract infection, amyloidosis (a disease caused by abnormal protein deposits in organs and tissues), or leprosy.
• Blood tests: If patients experience symptoms of factor X deficiency such as prolonged bleeding, doctors may diagnose the condition by performing blood tests. In a blood test, a doctor will draw a small amount of blood and check for the level and activity of clotting factor X. If it is missing or found at very low levels, a diagnosis can be made. Additionally, bleeding tests can be performed on blood to measure whether clotting is abnormally slow. At this time, genetic testing is not used to diagnose factor X deficiency because different mutations within the factor X gene cause this disease in different people.
• Blood tests may be performed on a developing fetus and after birth. However, there are serious risks associated with prenatal tests. Patients should discuss the potential health benefits and risks associated with these procedures with a healthcare professional before making any medical decisions. Blood samples taken in prenatal tests are subjected to the same tests as those taken from adults.
• Partial thromboplastin time (PTT) is a blood test that looks at how long it takes for blood to clot. It is prolonged in patients with factor X deficiency. In similar tests, prothrombin time will be prolonged, thrombin time will be normal, and viper venom (which contains a coagulant that interacts with factor X in the blood) time will be prolonged.

• Brain bleeding: If a patient experiences a head injury, even just a simple bump, internal bleeding in the brain may occur. In some cases, bleeding into the brain may occur spontaneously in people with factor X deficiency. Brain bleeding may result in headaches, fatigue, weakness, vomiting, or seizures, and may be life-threatening.
• Excessive bleeding: If external bleeding is not stopped in severe cases, excessive blood loss may lead to death. Bleeding into the stomach or intestines may occur spontaneously. This is most likely to occur in situations in which emergency treatment is not available.
• Hepatitis C virus (HCV) or HIV: In the past, donated blood used to obtain replacement clotting factor was not commonly screened, and the blood was frequently contaminated with the hepatitis C virus (HCV) or HIV. Therefore, many patients with hemophilia who received replacement clotting factor treatment were at risk for HCV or HIV infection. Care should always be taken to ensure that blood is screened for HCV, HIV, and other blood-borne infections before a blood transfusion begins.
• Joint pain: Some patients with factor X deficiency may experience pain and swelling in their joints, including in the knees, elbows, ankles, shoulders, and hips caused by internal bleeding in a joint. Joint bleeding may occur without any obvious injury, and in severe cases, joint bleeding may be long term and lead to permanent joint damage. Some patients may have difficulty walking or moving because of the pain and swelling. Chronic (long-term) joint deformities may be managed by an orthopedic specialist.
• Thrombosis: Thrombosis is the formation of a clot or thrombus inside a blood vessel, which obstructs the flow of blood through the circulatory system. Thrombosis may occur following prolonged treatment with clotting factors, especially in patients with liver disease. If prolonged fresh frozen plasma or prothrombin complex infusion is necessary, often a small amount of heparin (a blood thinner) may be added to decrease the risk of abnormal clot formation.

• General: Currently there is no cure for factor X deficiency. Treatment generally focuses on managing the symptoms and preventing complications. For patients with mild forms of factor X deficiency, minor cuts and scrapes can usually be treated by cleaning the cut, applying pressure, and putting on an ordinary bandage. Patients should tell their doctors if they are taking any prescription or over-the-counter drugs, herbs, or supplements because they may interact with treatment and worsen disease symptoms.
• Blood transfusions: Patients who suffer from severe bleeding may receive blood transfusions with donated blood. Anyone likely to receive blood derivatives as part of a treatment should be vaccinated against hepatitis A and B.
• Clotting factors: Individuals with more severe forms of factor X deficiency may require replacement of factor X using either fresh frozen plasma or prothrombin complex concentrates. Factor X is not commercially available as a concentrate but is part of fresh frozen plasma and prothrombin complex concentrates. Prothrombin complex concentrates are concentrates made from human plasma. They contain clotting factors II, VII, IX, and X; C protein; a small amount of heparin to protect against thrombosis (clot formation); and vitamin K. This therapy works by supplying the necessary enzymes to activate the clotting cascade.
• It is important to get fresh frozen plasma or factor X concentrates into the blood during sudden (acute) bleeding episodes or before surgery. To prevent a bleeding crisis, people with factor X deficiency and their families can be taught to administer fresh frozen plasma or prothrombin complex concentrates at the first signs of bleeding. People with severe forms of the disease may need to receive clotting therapy on a regular basis (two to three times per week). Patients with less severe forms may need to receive therapy only before an activity that may cause bleeding, such as surgery. Because some patients may need to regularly receive new infusions of clotting factor over the course of their lives, clotting factor replacement therapy may be very expensive.
• Lifestyle: People who have factor X deficiency are at a greater risk of uncontrolled bleeding if they do not eat a well-balanced diet, maintain a normal weight, and get enough sleep. Habits such as smoking and drinking alcohol are additional risk factors.
• Medications to avoid: Aspirin increases the risk of bleeding by inhibiting platelet function. Patients with factor X deficiency should therefore not take aspirin or blood-thinning medications.
• Physical activity: People with factor X deficiency should avoid contact sports like boxing, football, and hockey due to the risk of serious bleeding. Protective gear is available for children with factor X deficiency to help reduce the risk of injury and damage to internal organs. These include knee and elbow pads, helmets, and padded shorts.
• Surgery: If the disorder is caused by amyloidosis, a disease caused by proteins building up in tissues and organs, surgery to remove the spleen may be necessary.
• Vitamin K: Low levels of vitamin K may lead to increased bleeding, especially in infants. This is why newborns typically receive injections of vitamin K shortly after birth. Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, and green peas, and in foods such as beans, olives, canola oil, soybeans, meat, cereals, and dairy products. Individuals with factor X deficiency or their caregivers should talk to a qualified healthcare provider or pharmacist before taking vitamin K supplements. Patients already receiving coagulation therapy should not drastically change their eating habits without first consulting a healthcare provider. Significant changes in vitamin K consumption may have an impact on the effectiveness of treatment.

Note
: Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of Factor X deficiency. The therapies listed below have been studied for the prevention or treatment of bleeding or hemorrhaging. They should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies or preventive measures.

B

Good scientific evidence

• Rhubarb
  : Rhubarb has been used in traditional Chinese medicine for many disorders associated with the stomach and intestine, including upper gastrointestinal bleeding. Early studies suggest that rhubarb may help reduce upper gastrointestinal bleeding. Higher quality studies are necessary before a firm recommendation can be made. Avoid in individuals who are allergic or sensitive to rhubarb. Avoid using rhubarb for more than two weeks because it may induce tolerance in the colon, melanosis coli (a colon disorder), laxative dependence, pathological alterations in the colonic smooth muscles, and substantial loss of electrolytes. Rhubarb should be avoided in individuals with atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, pre-eclampsia (high blood pressure during pregnancy), kidney disorders, ulcerative colitis (colon tumors), and urinary problems. Avoid handling rhubarb leaves, as they may cause allergic skin reactions. Avoid use of rhubarb in children under age 12 because of the potential for water depletion. Use cautiously with bleeding disorders, cardiac conditions, coagulation therapy, constipation, history of kidney stones, or thin or brittle bones. Use cautiously if taking antipsychotic drugs or oral drugs, herbs, or supplements, including calcium, iron, and zinc. Avoid if pregnant or breastfeeding.

C

Unclear or conflicting scientific evidence

• Bellis perennis
  : Bellis perennis is a common European species of daisy. Bellis perennis has been used traditionally for treating wounds. In homeopathy, Bellis perennis is often used in combination with Arnica montana to treat bruising and trauma. Common daisy is widely used in homeopathy but is currently only rarely used in herbal medicine. Although homeopathic dosing is Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration (FDA), there is a lack of well-designed clinical trials to support claims for efficacy related to the use of Bellis perennis. More research is needed in this area. Avoid if allergic or hypersensitive to Bellis perennis, its constituents, or other plants of the Asteraceae/Compositae family, such as ragweed, chrysanthemums, marigolds, and dandelion. Use cautiously if taking anticoagulants or with bleeding disorders. Use cautiously if at risk for coagulation disorders such as strokes or blood clots. Use cautiously with anemia. Avoid use in children at traditional herbal doses because of the possibility of stunted growth. Avoid if pregnant or breastfeeding because of the possibility of growth retardation in the fetus and infant.
• Hypnosis
  : There is inconclusive evidence from early studies of hypnosis therapy for hemophilia, a bleeding disorder. Additional study is needed before a firm conclusion can be drawn. Use cautiously with mental illnesses such as psychosis or schizophrenia, bipolar disorder, multiple personality disorder, or dissociative disorders. Use cautiously with seizure disorders. Reported side effects include changes in skin temperature, heart rate, intestinal secretions and immune response, decreased blood pressure and brain wave patterns, disturbing memories, and false memories.
• Vitamin K
  : Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, and watercress, as well as in foods such as cabbage, cauliflower, green peas, beans, olives, canola oil, soybeans, meat, cereals, and dairy products. Vitamin K is essential for normal blood clotting. Because patients with Factor X deficiency cannot form blood clots normally, supplementation with vitamin K may be beneficial. Vitamin K deficiency in infants may lead to hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). Although almost half of newborns may have some degree of vitamin K deficiency, serious hemorrhagic disease is rare. Because vitamin K given by injection has been shown to prevent VKBD in newborns and young infants, the American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns. Oral dosing is not considered adequate as prevention, particularly in breastfeeding infants. Initial concerns of cancer risk were never proven and are generally not considered clinically relevant. In cases of true VKDB, bleeding may occur at injection sites, at the umbilicus, or in the gastrointestinal tract. Life-threatening bleeding into the head (intracranial) or in the area behind the lower abdomen (retroperitoneum) may also occur. Evaluation by a physician is imperative.

• General: There are currently no known means of preventing factor X deficiency. However, individuals can take steps to reduce the risk of excessive bleeding caused or made worse by certain lifestyle or nutritional habits. It is important for patients to tell their doctors if they are trying a new diet or taking any new prescription or over-the-counter drugs, herbs, or supplements (e.g., aspirin or related medicines, nonsteroidal anti-inflammatory drugs [NSAIDs], or vitamin K) because they may be causing the disorder or worsening symptoms. Regular dental care can help avoid dental surgeries, a risk factor for bleeding. Patients should wear a MedicAlert®
  bracelet or chain at all times inscribed with their type of coagulation problem.
• Lifestyle: People who have factor X deficiency are at a greater risk of uncontrolled bleeding if they do not eat a well-balanced diet, maintain a normal weight, and get enough sleep. Habits such as smoking and drinking alcohol are additional risk factors. Patients are advised to decrease alcohol consumption to reduce the risk of liver disease.
• Medications to avoid: Aspirin increases the risk of bleeding by inhibiting platelet function. Patients with factor X deficiency should therefore not take aspirin or blood-thinning medications.
• Physical activity: Maintaining adequate muscle mass by regular exercise can reduce the risk of bleeding. Patients should use high-quality sports equipment appropriate for any sport (helmet, elbow pads, kneepads, proper shoes, etc.). The most often recommended sports are swimming and cycling. Contact sports such as boxing, football, and hockey should be avoided because of the risk of serious injury resulting in severe bleeding.
• Vitamin K: Low levels of vitamin K in the blood may lead to an increased risk of bleeding because vitamin K is essential for proper clot formation. Therefore, patients should consume a healthy and balanced diet that is rich in vitamin K. Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, and green peas, and in foods such as beans, olives, canola oil, soybeans, meat, cereals, and dairy products. It is recommended that newborns receive an injection of vitamin K shortly after birth to avoid bleeding problems. Patients should consult their healthcare providers before taking vitamin K supplements. Patients who are already receiving coagulation therapy should not drastically change their eating habits unless they consult their healthcare providers first. Significant changes in vitamin K consumption may have an impact on the effectiveness of treatment.