Factor VII deficiency is a rare bleeding disorder characterized by a deficiency or dysfunction of coagulation Factor VII (FVII), which is an essential protein involved in the blood clotting process. This condition is also known as stable Factor VII deficiency or Alexander’s disease.
Factor VII deficiency can be inherited in an autosomal recessive manner, meaning that both parents must carry and pass on the defective gene for a child to have the disorder.
Factor VII is one of the clotting factors in the coagulation cascade, a series of complex reactions that help stop bleeding when a blood vessel is injured. When an injury occurs, Factor VII is activated, leading to the formation of a clot at the site of injury to prevent excessive bleeding.
Epidemiology
Factor VII deficiency is considered one of the rarest bleeding disorders among the inherited coagulation factor deficiencies. Its prevalence is estimated to be around 1 in 500,000 to 1 in 2 million individuals in the general population.
Factor VII deficiency has been reported worldwide, and there are no significant differences in prevalence among different geographical regions.
The severity of Factor VII deficiency can vary widely. Some individuals may have mild deficiencies with minimal bleeding tendencies, while others may have severe deficiencies that result in significant bleeding episodes.
Factor VII deficiency is typically inherited in an autosomal recessive pattern. This means that an individual needs to inherit a defective gene from both parents to develop the disorder.
Anatomy
Pathophysiology
Coagulation cascade is a complex series of reactions that occur in response to injury to a blood vessel. It involves multiple coagulation factors, each activating the next in a tightly regulated sequence.
Factor VII is one of the vitamin K-dependent coagulation factors (Factors II, VII, IX, and X) that are essential for the initiation of the coagulation cascade. It circulates in the blood as an inactive precursor and requires activation to become Factor VIIa, the active form.
Factor VII is activated by tissue factor (TF), also known as tissue factor III or thromboplastin, which is exposed at the site of vascular injury. The binding of Factor VII to TF triggers its conversion to Factor VIIa.
Etiology
The most common cause of Factor VII deficiency is an inherited autosomal recessive genetic mutation. Both parents must carry and pass on a defective gene for a child to be affected. Individuals who inherit two copies of the defective gene have a complete deficiency, while those who inherit one defective gene have a partial deficiency.
Liver is the primary site of synthesis of coagulation factors, including Factor VII. Liver diseases such as cirrhosis or liver failure can reduce the production of Factor VII and lead to acquired Factor VII deficiency.
Vitamin K is essential to produce functional coagulation factors, including Factor VII. Deficiency in vitamin K, which can occur due to inadequate intake, malabsorption, or medication interactions, can result in acquired Factor VII deficiency.
Genetics
Prognostic Factors
The severity of Factor VII deficiency is a crucial prognostic factor. Individuals with mild deficiencies may have minimal bleeding tendencies and can often lead relatively normal lives without significant complications.
Bleeding into the joints and muscles can cause significant pain, joint damage, and mobility issues. The presence and frequency of joint and muscle bleeding episodes are considered as important prognostic factors.
The frequency and severity of bleeding episodes are essential prognostic factors. Individuals with severe Factor VII deficiency may experience more frequent and severe bleeding episodes, which could potentially lead to more significant health concerns.
Clinical History
Age Group:
Factor VII deficiency may be detected during the neonatal period or early infancy, especially in individuals with complete deficiency. Bleeding symptoms in neonates and infants can include prolonged bleeding from the umbilical cord stump after birth or excessive bleeding from minor injuries.
Children with Factor VII deficiency may experience bleeding episodes after minor trauma, such as cuts, bruises, or dental procedures. The severity of bleeding symptoms can vary, and some children may have mild forms of the condition, which might go undiagnosed until later in life.
Factor VII deficiency can continue to affect individuals into adolescence and young adulthood. During this period, bleeding symptoms may become more noticeable, especially after injuries or surgeries.
Physical Examination
Joints Examination: Joint examination is essential, particularly in individuals with a history of joint bleeding or suspected hemarthrosis. The provider will assess for signs of joint swelling, tenderness, warmth, or limited range of motion.
Vital Signs: Blood pressure, heart rate, and other vital signs will be measured to assess the individual’s overall health status.
Bleeding Examination: The provider will inquire about the frequency, duration, and severity of any bleeding episodes, including nosebleeds, gum bleeding, gastrointestinal bleeding, or any other unusual bleeding.
Muscles Examination: Muscle examination may be necessary, especially in individuals with a history of muscle bleeds or suspected hematomas. The provider will look for signs of localized swelling, tenderness, or hardness in the muscles.
Age group
Associated comorbidity
Repeated joint bleeding can lead to chronic joint damage, especially if left untreated or inadequately managed. This can result in limited joint mobility, pain, and joint deformities.
Bleeding into muscles can lead to localized swelling, pain, and inflammation. Recurrent muscle bleeding can cause muscle weakness and affect mobility.Delayed Wound Healing: Prolonged bleeding after injuries or surgeries can lead to delayed wound healing and increase the risk of infection.
Severe Factor VII deficiency, especially in cases of complete deficiency, can carry a risk of intracranial hemorrhage (bleeding within the skull), particularly after head trauma. Intracranial bleeding can be life-threatening and may lead to neurological complications.
Associated activity
Acuity of presentation
Individuals with mild Factor VII deficiency may have a slightly reduced level of Factor VII, leading to mild bleeding tendencies. The bleeding episodes in these cases are often mild and may include easy bruising, nosebleeds, or prolonged bleeding after minor injuries or surgeries.
Individuals with moderate Factor VII deficiency may experience more frequent or more prolonged bleeding episodes. They may present with bleeding from the gums, excessive bleeding after dental procedures, and joint or muscle bleeds.
Differential Diagnoses
Von Willebrand Disease (VWD): VWD is the most common inherited bleeding disorder, characterized by deficiencies or abnormalities in von Willebrand factor (VWF), a protein involved in platelet function and stabilization of clotting factors. VWD can cause symptoms such as nosebleeds, mucosal bleeding, and heavy menstrual bleeding.
Hemophilia A and B: Hemophilia A and B are two other common inherited bleeding disorders caused by deficiencies of coagulation Factor VIII and Factor IX, respectively. These disorders can present with similar symptoms, including prolonged bleeding after injuries, joint bleeding, and easy bruising.
Vitamin K Deficiency: Vitamin K is essential for the synthesis of several coagulation factors, including Factor VII. A deficiency of vitamin K can lead to acquired Factor VII deficiency and result in bleeding manifestations.
Disseminated Intravascular Coagulation (DIC): DIC is a condition characterized by widespread activation of the coagulation system and the consumption of clotting factors, leading to both clotting and bleeding.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Prophylactic Treatment: Prophylactic treatment involves regular infusions of clotting factor concentrates to prevent bleeding episodes. This approach is commonly used in individuals with severe Factor VII deficiency who have a history of frequent or severe bleeding episodes.
Surgical Prophylaxis: Prior to surgery or invasive procedures, individuals with Factor VII deficiency may receive prophylactic Factor VIIa infusions to minimize the risk of bleeding during and after the procedure.
Desmopressin (DDAVP) Therapy: In some cases of mild Factor VII deficiency, the synthetic hormone desmopressin (DDAVP) may be used to stimulate the release of stored Factor VII in the body, temporarily raising Factor VII levels.
Management of Bleeding Episodes: In the event of a bleeding episode, the prompt administration of clotting factor concentrates is essential to control bleeding and prevent complications. Healthcare providers may instruct affected individuals or their caregivers on how to administer treatment at home or when to seek medical attention.
Injury Protection: Since individuals with Factor VII deficiency are prone to bleeding episodes, it is crucial to take measures to prevent injuries. This may include using safety equipment, avoiding contact with sports or high-risk activities, and being cautious during everyday activities to minimize the risk of falls or accidents.
Dental Care: Dental procedures can lead to bleeding episodes in individuals with Factor VII deficiency. It is essential to inform the dentist about the condition before any dental work and discuss appropriate management, such as preoperative factor infusions.
Surgery management: Prior to any surgical procedures or invasive interventions, it is essential to coordinate with the healthcare team to develop a comprehensive plan for managing bleeding risks.
Joint Care: Individuals with a history of joint bleeding should take measures to protect their joints and avoid activities that may exacerbate joint damage.
Lifestyle modification: Adopting a healthy lifestyle can improve overall health and well-being. This includes maintaining a balanced diet rich in iron and other nutrients, getting regular exercise, and avoiding smoking or excessive alcohol consumption.
Use of Plasma-Derived Factor VII Concentrate
Plasma-Derived Factor VII Concentrate: Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII.
Plasma-derived Factor VII concentrate is also administered intravenously. It is typically reconstituted with a suitable diluent before the infusion.
Plasma-derived Factor VII concentrate is one of the main pharmaceutical agents used for treating Factor VII deficiency. It is an effective treatment option for controlling bleeding episodes in individuals with this bleeding disorder.
Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII. It is prepared from pooled plasma obtained from healthy blood donors who have been screened for infectious diseases.
Use of <a class="wpil_keyword_link" href="https://medtigo.com/drug/factor-xiii-a-subunit-recombinant" title="Recombinant" data-wpil-keyword-link="linked">Recombinant</a> Activated Factor VII
Recombinant Activated Factor VII (rFVIIa): It is a synthetic form of Factor VIIa, the active form of Factor VII, and is produced through genetic engineering. rFVIIa is an effective treatment option for controlling bleeding episodes in individuals with Factor VII deficiency.
rFVIIa is typically administered intravenously (IV) into a vein. It can also be given through continuous infusion using an infusion pump, depending on the specific situation and the healthcare provider’s recommendation.
rFVIIa is indicated for the treatment of bleeding episodes in individuals with Factor VII deficiency. It is effective in managing various bleeding manifestations, including spontaneous bleeding, joint bleeds, muscle bleeds, and bleeding after surgeries or injuries.
Use of blood products
These agents are indicated for the correction of abnormal hemostatic parameters.
Fresh Frozen Plasma (FFP): FFP is a blood product that contains a mixture of various coagulation factors, including Factor VII. While FFP may be used in certain situations to manage bleeding in individuals with other clotting factor deficiencies, it is not considered the treatment of choice for Factor VII deficiency.
Factor IX Complex: Factor IX complex products are clotting factor concentrates that contain a combination of coagulation factors, including Factor IX, Factor II (prothrombin), Factor X, and low levels of Factor VII.
Role of Antifibrinolytic agents
Antifibrinolytic agents, such as tranexamic acid and aminocaproic acid, can play a supportive role in the treatment of Factor VII deficiency, especially in managing bleeding episodes. These agents work by preventing the breakdown of blood clots, which can help stabilize clots and reduce bleeding.
Aminocaproic acid: It is an antifibrinolytic agent commonly used to manage bleeding episodes in various bleeding disorders, including Factor VII deficiency. It works by inhibiting the breakdown of blood clots, thereby promoting clot stability and reducing bleeding.
Preparation of Clotting Factor Concentrate: Clotting factor concentrates, such as recombinant activated Factor VII (rFVIIa) or plasma-derived Factor VII concentrate, are prepared as a freeze-dried powder or a liquid formulation.
Reconstitution: If the clotting factor concentrate is in freeze-dried form, it needs to be reconstituted with sterile water or another specified diluent according to the manufacturer’s instructions. This creates a solution ready for intravenous infusion.
Intravenous Infusion: The clotting factor concentrate is administered directly into a vein (intravenously) using a sterile needle and syringe or an infusion pump. The infusion is typically given over a specific period, depending on the dose and the individual’s condition.
use-of-phases-in-managing-factor-vii-deficiency
Diagnosis Phase: The first phase is accurate diagnosis. This involves a thorough evaluation of bleeding symptoms, medical history, family history, and laboratory tests to measure Factor VII activity and antigen levels.
Comprehensive Care Phase: A comprehensive care plan is developed based on the individual’s specific needs, severity of Factor VII deficiency, and bleeding history. The plan may include on-demand or prophylactic clotting factor infusions, DDAVP therapy and guidelines for managing bleeding episodes.
Prophylactic Treatment Phase: Prophylactic treatment with clotting factor concentrates may be recommended for individuals with severe Factor VII deficiency and a history of frequent or severe bleeding episodes. Regular infusions help maintain stable Factor VII levels and reduce the risk of spontaneous bleeding.
Surgical Intervention: Prior to surgical procedures or invasive interventions, a comprehensive plan is developed to manage bleeding risks. Prophylactic infusions of clotting factor concentrates may be given before and after the procedure to prevent bleeding complications.
Regular Follow-ups: Regular follow-ups with healthcare providers, including hematologists or specialized hemophilia treatment centers, are essential for monitoring Factor VII levels, assessing bleeding symptoms, adjusting treatment as needed, and addressing any concerns or complications.
Factor VII deficiency is a rare bleeding disorder characterized by a deficiency or dysfunction of coagulation Factor VII (FVII), which is an essential protein involved in the blood clotting process. This condition is also known as stable Factor VII deficiency or Alexander’s disease.
Factor VII deficiency can be inherited in an autosomal recessive manner, meaning that both parents must carry and pass on the defective gene for a child to have the disorder.
Factor VII is one of the clotting factors in the coagulation cascade, a series of complex reactions that help stop bleeding when a blood vessel is injured. When an injury occurs, Factor VII is activated, leading to the formation of a clot at the site of injury to prevent excessive bleeding.
Factor VII deficiency is considered one of the rarest bleeding disorders among the inherited coagulation factor deficiencies. Its prevalence is estimated to be around 1 in 500,000 to 1 in 2 million individuals in the general population.
Factor VII deficiency has been reported worldwide, and there are no significant differences in prevalence among different geographical regions.
The severity of Factor VII deficiency can vary widely. Some individuals may have mild deficiencies with minimal bleeding tendencies, while others may have severe deficiencies that result in significant bleeding episodes.
Factor VII deficiency is typically inherited in an autosomal recessive pattern. This means that an individual needs to inherit a defective gene from both parents to develop the disorder.
Coagulation cascade is a complex series of reactions that occur in response to injury to a blood vessel. It involves multiple coagulation factors, each activating the next in a tightly regulated sequence.
Factor VII is one of the vitamin K-dependent coagulation factors (Factors II, VII, IX, and X) that are essential for the initiation of the coagulation cascade. It circulates in the blood as an inactive precursor and requires activation to become Factor VIIa, the active form.
Factor VII is activated by tissue factor (TF), also known as tissue factor III or thromboplastin, which is exposed at the site of vascular injury. The binding of Factor VII to TF triggers its conversion to Factor VIIa.
The most common cause of Factor VII deficiency is an inherited autosomal recessive genetic mutation. Both parents must carry and pass on a defective gene for a child to be affected. Individuals who inherit two copies of the defective gene have a complete deficiency, while those who inherit one defective gene have a partial deficiency.
Liver is the primary site of synthesis of coagulation factors, including Factor VII. Liver diseases such as cirrhosis or liver failure can reduce the production of Factor VII and lead to acquired Factor VII deficiency.
Vitamin K is essential to produce functional coagulation factors, including Factor VII. Deficiency in vitamin K, which can occur due to inadequate intake, malabsorption, or medication interactions, can result in acquired Factor VII deficiency.
The severity of Factor VII deficiency is a crucial prognostic factor. Individuals with mild deficiencies may have minimal bleeding tendencies and can often lead relatively normal lives without significant complications.
Bleeding into the joints and muscles can cause significant pain, joint damage, and mobility issues. The presence and frequency of joint and muscle bleeding episodes are considered as important prognostic factors.
The frequency and severity of bleeding episodes are essential prognostic factors. Individuals with severe Factor VII deficiency may experience more frequent and severe bleeding episodes, which could potentially lead to more significant health concerns.
Age Group:
Factor VII deficiency may be detected during the neonatal period or early infancy, especially in individuals with complete deficiency. Bleeding symptoms in neonates and infants can include prolonged bleeding from the umbilical cord stump after birth or excessive bleeding from minor injuries.
Children with Factor VII deficiency may experience bleeding episodes after minor trauma, such as cuts, bruises, or dental procedures. The severity of bleeding symptoms can vary, and some children may have mild forms of the condition, which might go undiagnosed until later in life.
Factor VII deficiency can continue to affect individuals into adolescence and young adulthood. During this period, bleeding symptoms may become more noticeable, especially after injuries or surgeries.
Joints Examination: Joint examination is essential, particularly in individuals with a history of joint bleeding or suspected hemarthrosis. The provider will assess for signs of joint swelling, tenderness, warmth, or limited range of motion.
Vital Signs: Blood pressure, heart rate, and other vital signs will be measured to assess the individual’s overall health status.
Bleeding Examination: The provider will inquire about the frequency, duration, and severity of any bleeding episodes, including nosebleeds, gum bleeding, gastrointestinal bleeding, or any other unusual bleeding.
Muscles Examination: Muscle examination may be necessary, especially in individuals with a history of muscle bleeds or suspected hematomas. The provider will look for signs of localized swelling, tenderness, or hardness in the muscles.
Repeated joint bleeding can lead to chronic joint damage, especially if left untreated or inadequately managed. This can result in limited joint mobility, pain, and joint deformities.
Bleeding into muscles can lead to localized swelling, pain, and inflammation. Recurrent muscle bleeding can cause muscle weakness and affect mobility.Delayed Wound Healing: Prolonged bleeding after injuries or surgeries can lead to delayed wound healing and increase the risk of infection.
Severe Factor VII deficiency, especially in cases of complete deficiency, can carry a risk of intracranial hemorrhage (bleeding within the skull), particularly after head trauma. Intracranial bleeding can be life-threatening and may lead to neurological complications.
Individuals with mild Factor VII deficiency may have a slightly reduced level of Factor VII, leading to mild bleeding tendencies. The bleeding episodes in these cases are often mild and may include easy bruising, nosebleeds, or prolonged bleeding after minor injuries or surgeries.
Individuals with moderate Factor VII deficiency may experience more frequent or more prolonged bleeding episodes. They may present with bleeding from the gums, excessive bleeding after dental procedures, and joint or muscle bleeds.
Von Willebrand Disease (VWD): VWD is the most common inherited bleeding disorder, characterized by deficiencies or abnormalities in von Willebrand factor (VWF), a protein involved in platelet function and stabilization of clotting factors. VWD can cause symptoms such as nosebleeds, mucosal bleeding, and heavy menstrual bleeding.
Hemophilia A and B: Hemophilia A and B are two other common inherited bleeding disorders caused by deficiencies of coagulation Factor VIII and Factor IX, respectively. These disorders can present with similar symptoms, including prolonged bleeding after injuries, joint bleeding, and easy bruising.
Vitamin K Deficiency: Vitamin K is essential for the synthesis of several coagulation factors, including Factor VII. A deficiency of vitamin K can lead to acquired Factor VII deficiency and result in bleeding manifestations.
Disseminated Intravascular Coagulation (DIC): DIC is a condition characterized by widespread activation of the coagulation system and the consumption of clotting factors, leading to both clotting and bleeding.
Prophylactic Treatment: Prophylactic treatment involves regular infusions of clotting factor concentrates to prevent bleeding episodes. This approach is commonly used in individuals with severe Factor VII deficiency who have a history of frequent or severe bleeding episodes.
Surgical Prophylaxis: Prior to surgery or invasive procedures, individuals with Factor VII deficiency may receive prophylactic Factor VIIa infusions to minimize the risk of bleeding during and after the procedure.
Desmopressin (DDAVP) Therapy: In some cases of mild Factor VII deficiency, the synthetic hormone desmopressin (DDAVP) may be used to stimulate the release of stored Factor VII in the body, temporarily raising Factor VII levels.
Management of Bleeding Episodes: In the event of a bleeding episode, the prompt administration of clotting factor concentrates is essential to control bleeding and prevent complications. Healthcare providers may instruct affected individuals or their caregivers on how to administer treatment at home or when to seek medical attention.
Injury Protection: Since individuals with Factor VII deficiency are prone to bleeding episodes, it is crucial to take measures to prevent injuries. This may include using safety equipment, avoiding contact with sports or high-risk activities, and being cautious during everyday activities to minimize the risk of falls or accidents.
Dental Care: Dental procedures can lead to bleeding episodes in individuals with Factor VII deficiency. It is essential to inform the dentist about the condition before any dental work and discuss appropriate management, such as preoperative factor infusions.
Surgery management: Prior to any surgical procedures or invasive interventions, it is essential to coordinate with the healthcare team to develop a comprehensive plan for managing bleeding risks.
Joint Care: Individuals with a history of joint bleeding should take measures to protect their joints and avoid activities that may exacerbate joint damage.
Lifestyle modification: Adopting a healthy lifestyle can improve overall health and well-being. This includes maintaining a balanced diet rich in iron and other nutrients, getting regular exercise, and avoiding smoking or excessive alcohol consumption.
Plasma-Derived Factor VII Concentrate: Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII.
Plasma-derived Factor VII concentrate is also administered intravenously. It is typically reconstituted with a suitable diluent before the infusion.
Plasma-derived Factor VII concentrate is one of the main pharmaceutical agents used for treating Factor VII deficiency. It is an effective treatment option for controlling bleeding episodes in individuals with this bleeding disorder.
Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII. It is prepared from pooled plasma obtained from healthy blood donors who have been screened for infectious diseases.
Recombinant Activated Factor VII (rFVIIa): It is a synthetic form of Factor VIIa, the active form of Factor VII, and is produced through genetic engineering. rFVIIa is an effective treatment option for controlling bleeding episodes in individuals with Factor VII deficiency.
rFVIIa is typically administered intravenously (IV) into a vein. It can also be given through continuous infusion using an infusion pump, depending on the specific situation and the healthcare provider’s recommendation.
rFVIIa is indicated for the treatment of bleeding episodes in individuals with Factor VII deficiency. It is effective in managing various bleeding manifestations, including spontaneous bleeding, joint bleeds, muscle bleeds, and bleeding after surgeries or injuries.
These agents are indicated for the correction of abnormal hemostatic parameters.
Fresh Frozen Plasma (FFP): FFP is a blood product that contains a mixture of various coagulation factors, including Factor VII. While FFP may be used in certain situations to manage bleeding in individuals with other clotting factor deficiencies, it is not considered the treatment of choice for Factor VII deficiency.
Factor IX Complex: Factor IX complex products are clotting factor concentrates that contain a combination of coagulation factors, including Factor IX, Factor II (prothrombin), Factor X, and low levels of Factor VII.
Antifibrinolytic agents, such as tranexamic acid and aminocaproic acid, can play a supportive role in the treatment of Factor VII deficiency, especially in managing bleeding episodes. These agents work by preventing the breakdown of blood clots, which can help stabilize clots and reduce bleeding.
Aminocaproic acid: It is an antifibrinolytic agent commonly used to manage bleeding episodes in various bleeding disorders, including Factor VII deficiency. It works by inhibiting the breakdown of blood clots, thereby promoting clot stability and reducing bleeding.
Preparation of Clotting Factor Concentrate: Clotting factor concentrates, such as recombinant activated Factor VII (rFVIIa) or plasma-derived Factor VII concentrate, are prepared as a freeze-dried powder or a liquid formulation.
Reconstitution: If the clotting factor concentrate is in freeze-dried form, it needs to be reconstituted with sterile water or another specified diluent according to the manufacturer’s instructions. This creates a solution ready for intravenous infusion.
Intravenous Infusion: The clotting factor concentrate is administered directly into a vein (intravenously) using a sterile needle and syringe or an infusion pump. The infusion is typically given over a specific period, depending on the dose and the individual’s condition.
Diagnosis Phase: The first phase is accurate diagnosis. This involves a thorough evaluation of bleeding symptoms, medical history, family history, and laboratory tests to measure Factor VII activity and antigen levels.
Comprehensive Care Phase: A comprehensive care plan is developed based on the individual’s specific needs, severity of Factor VII deficiency, and bleeding history. The plan may include on-demand or prophylactic clotting factor infusions, DDAVP therapy and guidelines for managing bleeding episodes.
Prophylactic Treatment Phase: Prophylactic treatment with clotting factor concentrates may be recommended for individuals with severe Factor VII deficiency and a history of frequent or severe bleeding episodes. Regular infusions help maintain stable Factor VII levels and reduce the risk of spontaneous bleeding.
Surgical Intervention: Prior to surgical procedures or invasive interventions, a comprehensive plan is developed to manage bleeding risks. Prophylactic infusions of clotting factor concentrates may be given before and after the procedure to prevent bleeding complications.
Regular Follow-ups: Regular follow-ups with healthcare providers, including hematologists or specialized hemophilia treatment centers, are essential for monitoring Factor VII levels, assessing bleeding symptoms, adjusting treatment as needed, and addressing any concerns or complications.
Factor VII deficiency is a rare bleeding disorder characterized by a deficiency or dysfunction of coagulation Factor VII (FVII), which is an essential protein involved in the blood clotting process. This condition is also known as stable Factor VII deficiency or Alexander’s disease.
Factor VII deficiency can be inherited in an autosomal recessive manner, meaning that both parents must carry and pass on the defective gene for a child to have the disorder.
Factor VII is one of the clotting factors in the coagulation cascade, a series of complex reactions that help stop bleeding when a blood vessel is injured. When an injury occurs, Factor VII is activated, leading to the formation of a clot at the site of injury to prevent excessive bleeding.
Factor VII deficiency is considered one of the rarest bleeding disorders among the inherited coagulation factor deficiencies. Its prevalence is estimated to be around 1 in 500,000 to 1 in 2 million individuals in the general population.
Factor VII deficiency has been reported worldwide, and there are no significant differences in prevalence among different geographical regions.
The severity of Factor VII deficiency can vary widely. Some individuals may have mild deficiencies with minimal bleeding tendencies, while others may have severe deficiencies that result in significant bleeding episodes.
Factor VII deficiency is typically inherited in an autosomal recessive pattern. This means that an individual needs to inherit a defective gene from both parents to develop the disorder.
Coagulation cascade is a complex series of reactions that occur in response to injury to a blood vessel. It involves multiple coagulation factors, each activating the next in a tightly regulated sequence.
Factor VII is one of the vitamin K-dependent coagulation factors (Factors II, VII, IX, and X) that are essential for the initiation of the coagulation cascade. It circulates in the blood as an inactive precursor and requires activation to become Factor VIIa, the active form.
Factor VII is activated by tissue factor (TF), also known as tissue factor III or thromboplastin, which is exposed at the site of vascular injury. The binding of Factor VII to TF triggers its conversion to Factor VIIa.
The most common cause of Factor VII deficiency is an inherited autosomal recessive genetic mutation. Both parents must carry and pass on a defective gene for a child to be affected. Individuals who inherit two copies of the defective gene have a complete deficiency, while those who inherit one defective gene have a partial deficiency.
Liver is the primary site of synthesis of coagulation factors, including Factor VII. Liver diseases such as cirrhosis or liver failure can reduce the production of Factor VII and lead to acquired Factor VII deficiency.
Vitamin K is essential to produce functional coagulation factors, including Factor VII. Deficiency in vitamin K, which can occur due to inadequate intake, malabsorption, or medication interactions, can result in acquired Factor VII deficiency.
The severity of Factor VII deficiency is a crucial prognostic factor. Individuals with mild deficiencies may have minimal bleeding tendencies and can often lead relatively normal lives without significant complications.
Bleeding into the joints and muscles can cause significant pain, joint damage, and mobility issues. The presence and frequency of joint and muscle bleeding episodes are considered as important prognostic factors.
The frequency and severity of bleeding episodes are essential prognostic factors. Individuals with severe Factor VII deficiency may experience more frequent and severe bleeding episodes, which could potentially lead to more significant health concerns.
Age Group:
Factor VII deficiency may be detected during the neonatal period or early infancy, especially in individuals with complete deficiency. Bleeding symptoms in neonates and infants can include prolonged bleeding from the umbilical cord stump after birth or excessive bleeding from minor injuries.
Children with Factor VII deficiency may experience bleeding episodes after minor trauma, such as cuts, bruises, or dental procedures. The severity of bleeding symptoms can vary, and some children may have mild forms of the condition, which might go undiagnosed until later in life.
Factor VII deficiency can continue to affect individuals into adolescence and young adulthood. During this period, bleeding symptoms may become more noticeable, especially after injuries or surgeries.
Joints Examination: Joint examination is essential, particularly in individuals with a history of joint bleeding or suspected hemarthrosis. The provider will assess for signs of joint swelling, tenderness, warmth, or limited range of motion.
Vital Signs: Blood pressure, heart rate, and other vital signs will be measured to assess the individual’s overall health status.
Bleeding Examination: The provider will inquire about the frequency, duration, and severity of any bleeding episodes, including nosebleeds, gum bleeding, gastrointestinal bleeding, or any other unusual bleeding.
Muscles Examination: Muscle examination may be necessary, especially in individuals with a history of muscle bleeds or suspected hematomas. The provider will look for signs of localized swelling, tenderness, or hardness in the muscles.
Repeated joint bleeding can lead to chronic joint damage, especially if left untreated or inadequately managed. This can result in limited joint mobility, pain, and joint deformities.
Bleeding into muscles can lead to localized swelling, pain, and inflammation. Recurrent muscle bleeding can cause muscle weakness and affect mobility.Delayed Wound Healing: Prolonged bleeding after injuries or surgeries can lead to delayed wound healing and increase the risk of infection.
Severe Factor VII deficiency, especially in cases of complete deficiency, can carry a risk of intracranial hemorrhage (bleeding within the skull), particularly after head trauma. Intracranial bleeding can be life-threatening and may lead to neurological complications.
Individuals with mild Factor VII deficiency may have a slightly reduced level of Factor VII, leading to mild bleeding tendencies. The bleeding episodes in these cases are often mild and may include easy bruising, nosebleeds, or prolonged bleeding after minor injuries or surgeries.
Individuals with moderate Factor VII deficiency may experience more frequent or more prolonged bleeding episodes. They may present with bleeding from the gums, excessive bleeding after dental procedures, and joint or muscle bleeds.
Von Willebrand Disease (VWD): VWD is the most common inherited bleeding disorder, characterized by deficiencies or abnormalities in von Willebrand factor (VWF), a protein involved in platelet function and stabilization of clotting factors. VWD can cause symptoms such as nosebleeds, mucosal bleeding, and heavy menstrual bleeding.
Hemophilia A and B: Hemophilia A and B are two other common inherited bleeding disorders caused by deficiencies of coagulation Factor VIII and Factor IX, respectively. These disorders can present with similar symptoms, including prolonged bleeding after injuries, joint bleeding, and easy bruising.
Vitamin K Deficiency: Vitamin K is essential for the synthesis of several coagulation factors, including Factor VII. A deficiency of vitamin K can lead to acquired Factor VII deficiency and result in bleeding manifestations.
Disseminated Intravascular Coagulation (DIC): DIC is a condition characterized by widespread activation of the coagulation system and the consumption of clotting factors, leading to both clotting and bleeding.
Prophylactic Treatment: Prophylactic treatment involves regular infusions of clotting factor concentrates to prevent bleeding episodes. This approach is commonly used in individuals with severe Factor VII deficiency who have a history of frequent or severe bleeding episodes.
Surgical Prophylaxis: Prior to surgery or invasive procedures, individuals with Factor VII deficiency may receive prophylactic Factor VIIa infusions to minimize the risk of bleeding during and after the procedure.
Desmopressin (DDAVP) Therapy: In some cases of mild Factor VII deficiency, the synthetic hormone desmopressin (DDAVP) may be used to stimulate the release of stored Factor VII in the body, temporarily raising Factor VII levels.
Management of Bleeding Episodes: In the event of a bleeding episode, the prompt administration of clotting factor concentrates is essential to control bleeding and prevent complications. Healthcare providers may instruct affected individuals or their caregivers on how to administer treatment at home or when to seek medical attention.
Injury Protection: Since individuals with Factor VII deficiency are prone to bleeding episodes, it is crucial to take measures to prevent injuries. This may include using safety equipment, avoiding contact with sports or high-risk activities, and being cautious during everyday activities to minimize the risk of falls or accidents.
Dental Care: Dental procedures can lead to bleeding episodes in individuals with Factor VII deficiency. It is essential to inform the dentist about the condition before any dental work and discuss appropriate management, such as preoperative factor infusions.
Surgery management: Prior to any surgical procedures or invasive interventions, it is essential to coordinate with the healthcare team to develop a comprehensive plan for managing bleeding risks.
Joint Care: Individuals with a history of joint bleeding should take measures to protect their joints and avoid activities that may exacerbate joint damage.
Lifestyle modification: Adopting a healthy lifestyle can improve overall health and well-being. This includes maintaining a balanced diet rich in iron and other nutrients, getting regular exercise, and avoiding smoking or excessive alcohol consumption.
Plasma-Derived Factor VII Concentrate: Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII.
Plasma-derived Factor VII concentrate is also administered intravenously. It is typically reconstituted with a suitable diluent before the infusion.
Plasma-derived Factor VII concentrate is one of the main pharmaceutical agents used for treating Factor VII deficiency. It is an effective treatment option for controlling bleeding episodes in individuals with this bleeding disorder.
Plasma-derived Factor VII concentrate is derived from human plasma and contains various coagulation factors, including Factor VII. It is prepared from pooled plasma obtained from healthy blood donors who have been screened for infectious diseases.
Recombinant Activated Factor VII (rFVIIa): It is a synthetic form of Factor VIIa, the active form of Factor VII, and is produced through genetic engineering. rFVIIa is an effective treatment option for controlling bleeding episodes in individuals with Factor VII deficiency.
rFVIIa is typically administered intravenously (IV) into a vein. It can also be given through continuous infusion using an infusion pump, depending on the specific situation and the healthcare provider’s recommendation.
rFVIIa is indicated for the treatment of bleeding episodes in individuals with Factor VII deficiency. It is effective in managing various bleeding manifestations, including spontaneous bleeding, joint bleeds, muscle bleeds, and bleeding after surgeries or injuries.
These agents are indicated for the correction of abnormal hemostatic parameters.
Fresh Frozen Plasma (FFP): FFP is a blood product that contains a mixture of various coagulation factors, including Factor VII. While FFP may be used in certain situations to manage bleeding in individuals with other clotting factor deficiencies, it is not considered the treatment of choice for Factor VII deficiency.
Factor IX Complex: Factor IX complex products are clotting factor concentrates that contain a combination of coagulation factors, including Factor IX, Factor II (prothrombin), Factor X, and low levels of Factor VII.
Antifibrinolytic agents, such as tranexamic acid and aminocaproic acid, can play a supportive role in the treatment of Factor VII deficiency, especially in managing bleeding episodes. These agents work by preventing the breakdown of blood clots, which can help stabilize clots and reduce bleeding.
Aminocaproic acid: It is an antifibrinolytic agent commonly used to manage bleeding episodes in various bleeding disorders, including Factor VII deficiency. It works by inhibiting the breakdown of blood clots, thereby promoting clot stability and reducing bleeding.
Preparation of Clotting Factor Concentrate: Clotting factor concentrates, such as recombinant activated Factor VII (rFVIIa) or plasma-derived Factor VII concentrate, are prepared as a freeze-dried powder or a liquid formulation.
Reconstitution: If the clotting factor concentrate is in freeze-dried form, it needs to be reconstituted with sterile water or another specified diluent according to the manufacturer’s instructions. This creates a solution ready for intravenous infusion.
Intravenous Infusion: The clotting factor concentrate is administered directly into a vein (intravenously) using a sterile needle and syringe or an infusion pump. The infusion is typically given over a specific period, depending on the dose and the individual’s condition.
Diagnosis Phase: The first phase is accurate diagnosis. This involves a thorough evaluation of bleeding symptoms, medical history, family history, and laboratory tests to measure Factor VII activity and antigen levels.
Comprehensive Care Phase: A comprehensive care plan is developed based on the individual’s specific needs, severity of Factor VII deficiency, and bleeding history. The plan may include on-demand or prophylactic clotting factor infusions, DDAVP therapy and guidelines for managing bleeding episodes.
Prophylactic Treatment Phase: Prophylactic treatment with clotting factor concentrates may be recommended for individuals with severe Factor VII deficiency and a history of frequent or severe bleeding episodes. Regular infusions help maintain stable Factor VII levels and reduce the risk of spontaneous bleeding.
Surgical Intervention: Prior to surgical procedures or invasive interventions, a comprehensive plan is developed to manage bleeding risks. Prophylactic infusions of clotting factor concentrates may be given before and after the procedure to prevent bleeding complications.
Regular Follow-ups: Regular follow-ups with healthcare providers, including hematologists or specialized hemophilia treatment centers, are essential for monitoring Factor VII levels, assessing bleeding symptoms, adjusting treatment as needed, and addressing any concerns or complications.
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