Hemophilia is a bleeding disorder in which the blood doesn’t clot properly. In this article, there will be a description of the differences between Hemophilia B and Hemophilia A.
Hemophilia is a lack or decrease of a clotting factor in the blood. There are several types of hemophilia because of distinct deficiencies in different clotting factors. The two most common types are hemophilia A and hemophilia B. The former is because of a lack or decrease in clotting factor VIII. In contrast, the latter is by a deficiency or reduction in clotting factor IX.
It is a rare disorder. The estimation in a 2019 study is that around 1,225,000 persons around the world have hemophilia. For every 100.000 births worldwide, there are approximately 30 new cases of hemophilia each year. Keep reading to learn more about hemophilia directly from the hand of an M.D.
What is Hemophilia?
Hemophilia is a bleeding disorder in which the blood lacks sufficient amounts of a clotting factor. Clotting factors are blood proteins involved in a chain reaction that leads to the production of a blood clot that stops the bleeding. Without clotting factors, the blood is unable to clot properly after an injury. Hemophilia A, also known as classic hemophilia, is because of a deficiency in clotting factor VIII. Hemophilia B or Christmas disease is a deficiency in clotting factor IX.
Furthermore, hemophilia is a genetic disease. Its existence grounds on a mutation in a gene that participates in the production of a particular clotting factor. These genes are in the X chromosome, and males have only one X chromosome and females have two. If a female has a defective gene in one of her X chromosomes, the genes in the other one serve as a backup. Therefore, females that have a hemophilia gene in just one of their X chromosomes will not undergo through the disease. However, they will act as carriers and pass on the disease to their children. The only way for a female to suffer from hemophilia is to inherit a hemophilia gene from both parents, which is extremely rare.
In most cases, hemophilia is an inherited disease, but some patients have no family history of hemophilia because all the previous carriers were asymptomatic females. Besides, in a third of all the hemophilia diagnoses, the disease does not come from the parents. It exists due to a spontaneous mutation.
Which is worse hemophilia A or B?
Both types of hemophilia classify into mild, moderate, and severe upon the plasma levels of clotting factors VIII and XI. Patients with plasma factor levels below 1% have severe hemophilia, those with levels between 1% and 5% have moderate hemophilia, and those with plasma factor levels over 5% have mild hemophilia.
In general, mild hemophilia patients only bleed after major trauma (i.e., car crash) or surgery, moderate hemophilia patients bleed after a minor injury, and severe hemophilia patients bleed spontaneously or after trivial trauma. For decades, scientists thought that severe hemophilia A was indistinguishable from severe hemophilia B new research disputes that claim.
Several studies performed in different countries have shown that hemophilia B tends to have milder symptoms than hemophilia A. Hemarthrosis (bleeding into a joint space), is one of the most frequent complications of severe hemophilia. Recurrent haemarthrosis leads to joint damage and permanent disability. A recent Italian study suggests that a hemophilia A patient has a three-fold risk of requiring orthopedic surgery compared with a hemophilia B patient. Another study done in Canada found that hemophilia B patients bleed less frequently and had less haemarthrosis than their hemophilia A counterparts.
Treatment for both types of hemophilia consists of replacement therapy, either from blood factor concentrates made from human blood or recombinant factors made in a laboratory. Nowadays, recombinant factor use is way more frequent than blood factor concentrate infusion. Evidence from various sources suggests that hemophilia B patients require approximately 20% percent less recombinant factors than hemophilia A patients. Data from the World Federation of Hemophilia reports a mean factor IX use of 0.29 per hemophilia B patient and a mean factor VIII use of 1,66 per hemophilia A patient. The evidence suggests less factor consumption in hemophilia B.
Why is hemophilia A more severe than hemophilia B?
Evidence suggests that hemophilia B has less severe mutations than hemophilia A. There are two types of genetic mutations: null mutations and non-null mutations. In a null mutation, the gene is not capable of producing the protein; hence, null mutations cause complete loss of function. In a non-null mutation, the gene will provide the protein but losing some of its capacity.
Null mutations are present in 80% percent of severe hemophilia A cases and 60% of severe hemophilia B cases. Non-null mutations have a milder clinical course because there is some degree of clotting factor function. Therefore, the severity of hemophilia A probably sources on a higher prevalence of null mutations.
Is hemophilia A or B more common?
Hemophilia A tends to be more severe than hemophilia. Unfortunately, it is also way more frequent. Hemophilia A affects one in every 5000 people and hemophilia B, one in every 25000 people, this makes hemophilia A around five times more prevalent than hemophilia B.
Neither hemophilia A nor hemophilia B distinguishes between race and ethnic groups. The rates of hemophilia among whites, African Americans, and Hispanics in the United States are practically the same.
Approximately 50-60% of all hemophilia A patients have a severe form of the disease, 25-30% have a moderate form, and the rest has the mild form of the disease.
Acquired hemophilia A is a rare form of the disease that affects 1 of every million people. Acquired hemophilia A occurs due to the development of autoantibodies against factor VIII. This unique form of the disease mostly affects older patients, usually over 60 years old.
Why is hemophilia A more common that B?
For an unknown reason, spontaneous mutations are more frequent in the genes that code factor VIII than in the ones that code factor IX. One-third of hemophilia A cases exist due to spontaneous mutations, while only one-fifth of hemophilia B cases happen because of spontaneous mutations. The difference in the rate of spontaneous mutations probably is the reason why hemophilia A is more frequent than B.
How is hemophilia A differentiated from hemophilia b?
As we saw, the primary difference between both types of hemophilia is that in hemophilia A there is a deficit in blood clotting factor VIII. In hemophilia B, there is a deficit in blood factor IX. Making the distinction between the two of them is vital because they need different recombinant factor injections. Factor VIII and factor IX last for distinct lengths of time in the blood, so patients with hemophilia A will require more frequent doses.
The studies that claim that hemophilia A is more severe than hemophilia b are based on large populations studied over several years. When it comes to individual patients, differentiating hemophilia A from hemophilia b without laboratory studies is impossible. In fact, without laboratory studies, it is also impossible to differentiate hemophilia from other bleeding disorders. At first glance, hemophilia might be mistaken for von Willebrand disease, because both are hereditary bleeding disorders with very similar symptoms and different treatments.
Thankfully, nowadays, the key diagnostic tests help physicians to navigate the tricky world of bleeding disorders.
How is hemophilia A and B diagnosed?
In a bleeding disorder, initial testing includes a complete blood cell count and coagulation studies. In hemophilia, platelet levels should be normal. A normal platelet level helps the attending physician discard platelet disorders such as idiopathic thrombocytopenic purpura and look for a problem in the blood clotting cascade.
Coagulation studies include thrombin time, prothrombin time (PT), and activated partial thromboplastin time (aPPT). In hemophilia, thrombin time and PT are usually normal, and the aPTT is prolonged. However, a normal aPTT does not exclude hemophilia because some cases of mild and moderate hemophilia have a normal aPTT.
The definitive diagnosis of hemophilia, as well as the differentiation between hemophilia A and hemophilia B, is through blood clotting factor assays. In these assays, the lab compares the clotting factor levels of the patient with a normal plasma standard designated to have 100% activity of factors VIII and IX, respectively. Factor VIII and factor IX values below 50% of the normal plasma standard are diagnostic of hemophilia.
In some cases, the diagnosis of hemophilia A can be tricky. Some conditions can artificially elevate factor VIII levels, masking the diagnosis. Some of these conditions include:
- Advanced age.
- High estrogen levels.
- Oral contraceptive use.
Can hemophilia a and b be prevented?
The prevention of genetic diseases like hemophilia A and B is not possible because, so far, doctors haven’t figured out a way to alter the DNA. However, couples that want to have a family can go through genetic screening to determine the risk of conceiving a child with a genetic disease such as hemophilia. Although some decades ago, hemophilia used to be a death sentence, now it’s a manageable disease, and many hemophilia patients go on to live long and happy lives.
Which individuals are most at risk for developing hemophilia A or B?
The male descendants of hemophilia carriers or suffers are the persons with the highest risk of developing the disease. In many cases, there is no family history of hemophilia because all the previous carriers were females without symptoms. However, one-third of patients will have a new, spontaneous mutation and be the first members of their family with hemophilia.
Why is hemophilia much more frequent in males?
Hemophilia is an X linked recessive disorder. Humans have two types of chromosomes: autosomal and sex chromosomes. Autosomal chromosomes come in pairs with identical morphology, in each pair, there will be one chromosome from each parent. Sex chromosomes don’t necessarily come in pairs, women have two X chromosomes while men have an X chromosome and a Y chromosome.
A recessive gene is one whose effects are masked by the presence of a dominant gene. For an autosomal recessive gene to be expressed, both chromosomes in the same pair need to have the recessive form of the gene.
When it comes to sex chromosomes gene expression varies with sex.
If a male has a hemophilia gene in his X chromosome, he will invariably express that gene because he doesn’t have another X chromosome with the dominant form of the gene. If a female has the hemophilia form of the gene in one of her X chromosomes and the normal form on the gene in other chromosomes, she will not express the hemophilia gene. She will, however, pass on the hemophilia gene to her children.
A woman can have hemophilia when both her parents are carriers of the hemophilia gene, and both X chromosomes have the hemophilia gene. However, this is extremely rare. Of the estimated 1.2 million people with hemophilia, 2,700 are women.
Why hemophilia is called the royal disease?
Before World War II, doctors knew very little about bleeding disorders. Before the 1940s, nobody even knew that blood factors existed. Hemophilia was common in European royal families during the 19th and 20th centuries and was baptized as the royal disease because of that.
Queen Victoria, who ruled England during the 19th century, passed it on to her offspring. One of her sons died of unexplained bleeding at a young age, and her two remaining daughters were carriers of the disease. The two princesses married into other European royal families and had children that carried or suffered from the disease. The case of Prince Alexei Romanov, the son of the last Russian Tsar, is the most famous case of hemophilia in a royal family.
Genetic testing of the remains of the last members of the Romanov family showed that they had the rare hemophilia B gene.
Is it a lifelong disease?
Right now, hemophilia is a lifelong illness. Currently, there is no cure for hemophilia, and patients require intravenous, blood clotting replacement therapy for life. In most patients, regular replacement therapy prevents most of the bleeding and offers the possibility of living a normal life. However, treatment is expensive and is not sufficiently effective for all patients.
If you diagnose hemophilia A or B, what therapies should you start immediately?
Nowadays, preventive or prophylactic treatment is the standard of care. The main objective of prophylactic treatment is to prevent bleeding and organ damage, particularly joint damage due to haemarthrosis. Modern care for hemophilia happens at home. Hospitalization is only for cases of severe bleeding. The idea is to allow patients to participate in normal activities that 70 years ago would have been impossible for a typical hemophilia patient.
The prophylactic approach consists of home administered regimens of factor concentrate infusions. Primary prophylaxis can begin before the age of three, before or after the first joint bleed. Studies suggest that prevention should start as early as possible; children that start prophylactic treatment before the age of three develop significantly less joint damage than those that begin prophylaxis after the age of 6.
The dose and interval of a hemophilia prophylactic regime should be tailored for each patient by a hemophilia specialist. The prophylactic regimen depends on the objectives of treatment, the economic resource available, and the venous access.
There are some drawbacks to prophylactic treatment. One of the main obstacles is the need for semi-permanent venous access and repeated venipunctures that can be unconformable and painful for patients. The elevated cost of prophylactic treatment is an important barrier that prevents universal access to prophylactic treatment.
What is an inhibitor?
Inhibitors are the worst enemies of hemophilia patients.
The primary treatment for hemophilia consists of replacement therapy with infused clotting factors. Inhibitors are antibodies that target infused foreign factors and destroy them. This happens because the immune system recognizes those factors as foreign molecules that pose a threat to the body. In most cases, inhibitors develop at some point between the 5th and 50th infusion. Inhibitor patients are twice as likely to be hospitalized for severe bleeding and are at increased risk of death.
Inhibitors are more frequent in hemophilia A. Around 30% of hemophilia A patients will develop inhibitors at some point in their lives compared with 8% of hemophilia B patients. However, half of hemophilia B inhibitor patients develop a life-threatening anaphylactic reaction towards infused factor IV.
A hemophilia patient without inhibitors heals from injuries quickly after a factor infusion, and an inhibitor patient can get worse after an infusion because inhibitors destroy the infused factors and also the small percentage of clotting factor the body manages to produce.
Not all patients with inhibitors have the same level of severity. Inhibitor levels are measured in titers. Patients with a low inhibitor titer can still benefit from factor VIII or IX products. They just need larger doses. Low titer inhibitors sometimes resolve spontaneously. Patients with a high inhibitor titer are not benefited from factor infusion, whatever the dose.
Hemophilia patients should check up for inhibitors at least once a year. Testing consists of measuring the aPTT shortly after factor infusion, a prolonged aPTT right after infusion means the patient has developed inhibitors. A positive Bethesda test confirms the diagnosis.
There are some risk factors in association with inhibitor development:
- Hemophilia A.
- Severe hemophilia.
- African American and Hispanic descent.
- Intensive factor therapy related to surgery or trauma.
- Gene mutation.
Can inhibitors be treated?
Treating a hemophilia patient with inhibitors is one of the most challenging things in hematology. The presence of inhibitors significantly increase the costs of care and can be a significant source of stress for both the patient and the physician.
Some treatment for inhibitors include the following:
- Increasing the dose of factor concentrates: Unfortunately, this only works in patients with low titer inhibitors.
- Immune tolerance induction therapy: This one basically means teaching the body to accept the factor as a normal part of the blood. Immune tolerance induction requires frequent high dose exposure to clotting factor concentrates for inducing tolerance. This process can take months or years. Tolerance induction treatment has a success rate of 70% in hemophilia A patients and 31% un hemophilia B patients.
- Bypassing Agents: These are special blood products that do not replace the missing clotting factor but go around it to form a normal blood clot. Recombinant factor VII is the go-to bypassing agent, and the drug can safely serve in hemophilia A and B patients.
- Emicizumab: This one is a monoclonal antibody that replaces factor VIII in the coagulation cascade. Emicizimab can also serve as a prophylactic treatment of patients without inhibitors.
How to treat active bleeding?
Prophylaxis isn’t 100% effective, and bleeding may occur in some cases. Minor bleeding from small cuts and bruises may respond to measures such as pressure and applying ice to the wound.
Moderate and severe bleeding requires immediate blood clotting factor concentrate infusion. Nose bleeds and other moderate hemorrhages require increasing clotting factor levels to the range of 50% and 60%. Life-threatening bleeds may require increasing factor VIII levels to 100% to stop the bleed.
Big, expanding joint bleeds can be extremely painful and may require aggressive narcotic therapy.
What foods to avoid if you have this condition?
Hemophilia doesn’t require any specific diet, and there is no need to avoid any particular foods if you have the disease. However, maintaining a healthy weight is essential for hemophilia patients. Being overweight puts on stress over the joints, and, as we know, joints can suffer significantly in hemophilia due to haemarthrosis. Extra pounds also increase the amount of factor replacement therapy required to prevent or stop a bleed. A healthy diet is essential in strengthening bones and joints to avoid permanent disability.
You may want to see: Anemia
What are the signs and symptoms of hemophilia?
Most hemophilia patients make their debut at a young age. Early bleeding symptoms include spontaneous bleeding, prolonged bleeding after a minor injury, and disproportional bleeding to minor trauma. In babies, bleeding starts with bruising when they are starting to crawl or during dentition. In many cases, the diagnosis is made after prolonged bleeding during circumcision.
Moreover, in cases of moderate or mild hemophilia, the disease can be diagnosed during adolescence or even adulthood. In these cases, the diagnosis arises after a major trauma followed by excessive bleeding; some examples include car crashes, tooth extractions, surgery, gunshots, and stabbing.
Joints are common sites of bleeding in hemophilia. Bleeding in the joints manifests with pain, stiffness, warmth, tingling, and crackling. Repeated bleeding episodes in the same joints produce a disabling pathology called hemophilic arthropathy, which may require surgical replacement of the joint.
Hemophilia can cause bleeding in any organ, bleeding in different organs causes different symptoms:
- Central nervous system: Intracranial hemorrhage produces an intense headache, vomiting, decreased consciousness, irritability, and a stiff neck.
- Gastrointestinal system: Gastrointestinal hemorrhage causes bloody vomit, abdominal pain, and bloody feces.
- Genitourinary system: Bloody urine and post-circumcision bleeding.
Other common symptoms include nose bleeds, bloody cough, difficulty breathing, and excessive bleeding during dental procedures.
Acquired hemophilia begins later in life, usually after the age of 60 or post-partum. Post-partum acquired hemophilia usually occurs three or five months after birth. This is a difficult condition to diagnose. Acquired hemophilia patients often experience life-threatening bleeding before the condition is recognized. In acquired hemophilia, joints aren’t the primary targets; gastrointestinal, genitourinary bleeding and subcutaneous bleeding are the most common manifestations of this disease.
Can hemophilia be mistaken for another bleeding disorder?
There are many congenital and acquired bleeding disorders that have similar or identical symptoms and may be mistaken for hemophilia. Some of these bleeding disorders include:
- Vitamin K deficiency
- Von Willebrand disease
- Physical child abuse
- Platelet disorders
- Liver disease
- Warfarin excess
- Factor XI deficiency
What are the possible future treatments?
Gene therapy promises to be the future of hemophilia treatment. Probably in a few years, the incurable nature of hemophilia will be a thing of the past.
Gene therapy consists of providing hemophilia patients a working copy of the genes that produce factor VIII or IX. The idea is to put the genes in protein-producing cells, and the ideal cells are the liver cells. Possible approaches to gene therapy include the following:
- EX Vivo gene therapy: This approach consists of extracting cells from the patient, genetically modify those cells to produce factor VIII, and reimplanting the modified cells into the liver of the patient.
- In vivo gene therapy: In this approach, scientists take a virus and alter it to include blood clotting factor DNA and then inject it directly into the patient.
- Nonautologous gene therapy: This one is similar to the ex vivo approach; the only difference is that the genetically modified cells are packaged into an immunoprotected device, which is later implanted into the patients.
Studies in animals with hemophilia have resulted in a permanent cure for hemophilia in some cases. Preliminary results in human clinical trials have shown. A 2017 study showed substantial rises in factor VIII levels and decreased bleeding rates in patients with severe hemophilia who received in vivo gene therapy. All participants achieved factor VIII activity levels that remained normal for a year and a half. During that year and a half, patients were able to cease replacement therapy, and none of them developed inhibitors during that period.
The dream of achieving a durable, if not lifelong, a cure for hemophilia might not be a dream in a few years. If the objective is achieved it would relieve a terrible burden of the backs of millions of patients.
What can you if you are having any symptoms of it?
This tool is a hemophilia symptoms checker. It will help to determine how likely it is for someone to have this condition. It is free, and it would only take a few minutes.