What is hemophilia and what are the most common symptoms of hemophilia?
Hemophilia (гемофилия) is an inherited blood clotting disorder in which the blood doesn’t clot normally (coagulopathy). In most cases, it is caused by congenital factor viii deficiency (missing clotting factor VIII) or congenital factor ix deficiency (missing clotting factor FIX). However, about 35% of cases are caused by a spontaneous gene mutation (defective factor VIII, or defective factor FIX). Patients with hemophilia may present with post-traumatic or spontaneous bleeding episodes, such as excessive or prolonged bleeding after minor cuts or injuries, prolonged bleeding after tooth brushing or flossing, bleeding gums, excessive bleeding after surgery or dental work, large unexplained bruises, deep bruises, nosebleeds without a known cause (epistaxis), excessive or prolonged menstrual blood flow (menorrhagia), blood in the urine (hematuria) or blood in the stool (hematochezia). Patients with hemophilia may also have episodes of internal bleeding that occur suddenly, and they may present with joint pain (arthralgia), or joint swelling, especially in the knees, ankles, and elbows.
How much of the population has hemophilia?
Hemophilia is a rare hematological disorder that affects 1 in 5,000 male births in the U.S. It affects about 29,000 individuals in the United States and about 400,000 worldwide.
In the United States, approximately 400 babies are born with hemophilia annually
Severity of Hemophilia A and B
How is hemophilia classified?
Hemophilia is classified into mild, moderate or severe depending on the levels of blood coagulation factors FVIII and FIX. In healthy people, the range of FVIII and FIX is between 50% and 150%. Hemophilia severity is classified as follows:
- Mild hemophilia, the levels of either FVIII or FIX range between 6% and 49%, it occurs in about 25 percent of people with hemophilia. Patients may have very few symptoms that occur only after injury, trauma, or surgery
- Moderate hemophilia, the levels of either FVIII or FIX range between 1% and 5%, it occurs in about 15 percent of people with hemophilia. In most cases, patients may have bleeding episodes that occur after minor injuries; however, rarely, spontaneous bleeding episodes may also occur.
- Severe hemophilia, the levels of either FVIII or FIX are less than 1%, it occurs in about 60 percent of people with hemophilia. In most cases, patients may have spontaneous bleeding episodes especially into joints and muscles. Recurrent hemarthrosis (bleeding into joints) can cause hemophilic arthropathy, a permanent joint disease that results in physical disability.
Hemarthrosis or joint bleeds are the main cause of hemophilic arthropathy that can occur in all severities of hemophilia. In individuals with mild or moderate hemophilia, trauma or injury usually initiates joint bleeding. However, spontaneous joint bleeds usually occur in individuals with severe hemophilia.
The first symptom of hemarthrosis is often painless tingling in the joint with no visible signs of bleeding. However, as bleeding continues, the joint swells and becomes painful to move and warm to touch. Joint swelling increases as bleeding continues into the joint and movement can be temporarily lost. At this point, pain can be severe. If left untreated, hemarthrosis can be exhausting, as chronic arthralgia, joint swelling, and permanent joint damage lead to limited mobility and decreased quality of life.
Severe hemophilia can cause severe anemia and unstable blood pressure due to soft tissue bleeding. Moreover, Bleeding into the muscles in the arms, legs, and thighs can cause compartment syndrome. Hemophiliacs with compartment syndrome often present with symptoms of pain, tingling or numbness due to nerve and tissue damage.
How many different types of hemophilia are there?
There are two main types of hemophilia:
- Hemophilia A (due to factor VIII deficiency)
- Hemophilia B (due to factor IX deficiency)
Both types of hemophilia are almost clinically identical and are associated with spontaneous bleeding episodes, such as internal bleeding into joints and muscles or external bleeding after minor cuts or injuries.
Both hemophilia A and B affect people of all backgrounds, regardless of gender, race or ethnicity.
How is hemophilia inherited?
Men who have hemophilia will pass their sex chromosomes to their sons and daughters. Daughters, therefore, will all be affected by the father’s altered X chromosome, and will all be carriers (obligate carriers) because males (XY) have one X-linked allele. Women have two two X-linked alleles (because females are XX), so female carriers of hemophilia (X+Xc) have one normal X chromosome and one X chromosome with the altered gene. If a male child inherits his mother’s altered X chromosome, he will have hemophilia. As such, Women who are carriers have a 50% chance to pass the hemophilia gene on to their children. So, their sons (XY) will have a 50% chance of having hemophilia and their daughters (XX) will have a 50% chance of being a carrier (X+Xc) and a 50% chance of being healthy!
What is Thrombosis?
Thrombosis is the process of forming a blood clot (a thrombus) within a blood vessel to prevent blood loss when a blood vessel is injured. A blood clot can cause a partial or total obstruction of the blood flow through an artery or a vein. Under pathological conditions, atherosclerotic emboli form due to atherosclerosis, which is a process in which fatty deposits (plaque) build up on the walls of the arteries and cause them to narrow and harden. Commonly, vascular occlusion or capillary bed occlusion (total obstruction of the blood flow through the vein, artery, or capillaries) occurs when a piece of clot or plaque (embolus) breaks off from an atherosclerotic plaque, which results in local ischemia. In most cases, local ischemia can result in an infarction.
Diagnosis of Hemophilia
How to diagnose hemophilia?
The diagnosis of hemophilia is made according to the following:
- Personal and family history of bleeding
- Laboratory testing
Two kinds of tests can be performed for female carriers:
Factor assays, A 1-stage APTT-based factor assay measures the amount of clotting factors VIII, IX, XI and XI in a person’s blood. However, some female carriers of hemophilia will have normal clotting factor levels. Therefore, this test has low specificity and can provide incorrect information to women who may indeed be carriers.
What is the cost of genetic testing?
Mutation analysis is a genetic test that offers high sensitivity and specificity, it is considered the most accurate method of genetic testing, as it looks directly for the altered gene that’s responsible for hemophilia. Genetic testing offer high sensitivity and specificity compared to Factor assays. Genetic testing can determine whether a woman is definitely a carrier of hemophilia or whether she is very unlikely to be a carrier. However, genetic testing is considered an expensive procedure that can cost from under $100 to more than $5,000. Moreover, these tests may not be available in all centers.
Treatment of Hemophilia
How to treat hemophilia?
Clotting factor replacement therapy using clotting Factor Concentrates that can be taken to increase the level of factor VIII or IX in the blood. Clotting factor concentrates can be made using human plasma or through rDNA technology.
- Plasma-derived products: plasma-derived products are made from donated plasma.
- Recombinant products: recombinant factor products are made in a laboratory using the rDNA technology, thus they offer a safer option than plasma-derived products because they avoid potential bloodborne transmission of pathogens, such as HBV and HIV. In the USA, treatment with recombinant products, is the standard of care.
Clotting agents may also be used in combination with replacement therapy for the prevention of bleeding, as they can stabilize the blood clots in place to stop bleeding.
What is hemophilia a caused by?
Hemophilia A (FVIII deficiency or classic hemophilia) is a common form of hemophilia caused by factor VIII deficiency.
What are the symptoms of hemophilia a?
Common symptoms of hemophilia a include:
- Prolonged bleeding in the mouth after tooth brushing or flossing, or after minor trauma
- Nosebleeds without a known cause (spontaneous epistaxis)
- Joint bleeding (spontaneous hemarthrosis)
- Subcutaneous ecchymosis (a subcutaneous spot of bleeding), especially in children
- Easy bruising
- Hematochezia (blood in the stool)
- Hematuria (blood in the urine)
- Haemorrhagic diathesis
In most cases, the diagnosis of severe hemophilia A is made due to excessive or prolonged bleeding after circumcision. Rarely, mild hemophilia is not diagnosed until adolescence or adulthood, as it causes so few symptoms.
Persons with mild or moderate hemophilia A do not typically have spontaneous bleeds; However, they tend to have bleeding episodes after injuries, dental procedures, or surgery.
How many people in the united states have hemophilia a?
Hemophilia A is a disease of males, as it occurs in approximately 1 in 5,000 male births and affects about 25,000 individuals in the United State; however, it may also occur in women. In approximately 65% of hemophilia A cases, the disease is inherited from a parent.
In approximately 35% of hemophilia A cases, the family history may be absent and the condition is often caused by a spontaneous gene mutation at the time of fertilization. This gene is carried on the X chromosome.
Hemophilia A affects people of all backgrounds, regardless of gender, race or ethnicity.
Individuals with Hemophilia A can face unique lifelong challenges that are often prevalent throughout the lifespan. However, children recently diagnosed with hemophilia who receive comprehensive treatment can now look forward to a near normal life expectancy because treatment has advanced remarkably in the past three decades.
Clotting Factor Concentrates are globally available; However, medicaments are released based on the severity of symptoms.
Hemophilia A requires enormous self adjustments, self-care and individualized ongoing support (ongoing professional support).
What is hemophilia b caused by?
Hemophilia B (Christmas disease) is a rare form of hemophilia caused factor IX deficiency due to a mutation in the corresponding gene.
What are the symptoms of hemophilia b?
Common symptoms of hemophilia b include:
- Prolonged bleeding in the mouth from a cut or bite, or after minor trauma
- Spontaneous epistaxis or nosebleeds without a known cause
- Joint bleeding (spontaneous hemarthrosis)
- Easy bruising
- Gastrointestinal tract
- Blood in the stool (hematochezia)
- Urinary tract hemorrhage
- Blood in the urine (hematuria)
Persons with mild hemophilia B do not typically have spontaneous bleeds; However, they may have prolonged or excessive bleeding after dental procedures, accidents, or surgery
How many people in the united states have hemophilia b?
This disease is the second most common form of hemophilia, it occurs in approximately 1 in 25,000 male births and affects about 4000 people in the United States.
Hemophilia B affects about 20 percent of people with hemophilia worldwide.
Christmas disease is an inherited-congenital blood disorder caused by factor IX deficiency, a protein necessary for blood to clot. In approximately 65% of hemophilia B cases, the disease is inherited from a parent. About 35 per cent of hemophilia B cases arise through spontaneous gene mutation.
In approximately 35% of cases, christmas disease may appear in families with no history due to a spontaneous genetic mutation.
Christmas disease is an X-linked condition that occurs in older adults, among persons ages 25 and older, as a result of a spontaneous gene mutation.
Treatments for hemophilia B mainly depend on the severity of symptoms. However, Christmas disease remains a real challenge for patients suffering from it, as it requires self-care and an ongoing professional support.