Medication
- The name Bethesda Units (BUs) was adopted at a conference that occurred in Bethesda, MD.
- Alternative Names: factor VIII deficiency; classic hemophilia; bleeding disorder – hemophilia A
- Famous people with hemophilia A:
Therapy
What kinds of hemophilia are there?
- Hemophilia A In the specific case of hemophilia A, also called classic hemophilia, the alterations will be those of hemophilia already mentioned, that is, it will present problems to ...
- Hemophilia B Hemophilia B or also known as Christmas disease, is caused by an involvement in the gene that gives rise to type IX clotting factor. ...
- Hemophilia C
Self-care
Table 2. Acquired hemophilia A Treatment Market Drivers in China Market Table 3. Acquired hemophilia A Treatment Market Restraints in China Market Table 4. Key Players of Acquired hemophilia A Treatment in China Market Table 5. Top Acquired hemophilia A ...
Nutrition
There is currently no cure for hemophilia. Effective treatments do exist, but they are expensive and involve lifelong injections several times per week to prevent bleeding.
What is the life expectancy for people with hemophilia?
What are the different types of treatment for hemophilia?
What is hemophilia and how is it treated?
Could a cure be coming for hemophilia?
What is the common treatment for hemophilia A?
Hemlibra® (also known as ACE 910 or emicizumab) It can be used to either prevent or reduce the frequency of bleeding episodes in people with hemophilia A. This treatment product can be given by injection under the skin.
What is the most common treatment option for hemophilia?
Treatment With Replacement Therapy. The main treatment for hemophilia is called replacement therapy. Concentrates of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) are slowly dripped or injected into a vein. These infusions help replace the clotting factor that's missing or low.
What is the mainstay of treatment for hemophilia?
Replacement of the congenitally deficient factor VIII or IX through plasma-derived or recombinant concentrates is the mainstay of treatment for hemophilia.
What is on-demand treatment for hemophilia?
On-demand therapy. On-demand therapy involves the use of clotting factor to treat bleeds after bleeding has started. In general, people with mild or moderate hemophilia, who tend to bleed less often, use this type of treatment.
Which treatments are currently available for individuals with hemophilia B?
Current Treatment Options Recombinant factor IX therapy is the recommended treatment for individuals with hemophilia B. In the U.S., the currently available recombinant factor IX products are BeneFIX, Rixubis, Ixinity, Alprolix Idelvion, and Rebinyn.
What does treatment of hemophilia often involve quizlet?
Treatment of hemophilia often involves: Transfusion of plasma or injections of missing clotting factor.
Is FFP used to treat hemophilia?
FFP is the first product used to treat patients with hemophilia C.
Why is FFP given in hemophilia?
In the late 1950s and much of the 1960s, fresh frozen plasma (FFP) was the mainstay of treatment for hemophilia A and hemophilia B. Each bag of FFP contained only miniscule amounts of factor VIII and factor IX, thus large volumes of intravenously administered FFP were needed to stop bleeding episodes.
How do you treat hemophilia with inhibitors?
About Inhibitors People with hemophilia, and many with VWD type 3, use treatment products called clotting factor concentrates (“factor”). These treatment products improve blood clotting, and they are used to stop or prevent a bleeding episode.
What is prophylaxis hemophilia A?
In haemophilia, prophylaxis can be defined as the administration of clotting factor concentrate in anticipation of or to prevent bleeding.
How is hemophilia diagnosed and treated?
Diagnosis includes screening tests and clotting factor tests. Screening tests are blood tests that show if the blood is clotting properly. Clotting factor tests, also called factor assays, are required to diagnose a bleeding disorder. This blood test shows the type of hemophilia and the severity.
How is hemophilia treated with gene therapy?
Gene therapy offers the potential for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX (FIX) following transfer of a functional gene to replace the hemophilic patient's own defective gene.
How to treat hemophilia A?
This is done by infusing (giving medication into a vein) a FVIII product into the affected person. When you infuse, FVIII concentrate, the FVIII is immediately available in the bloodstream, and your body can use it to stop or prevent the bleeding.
When did cloning of FVIII and FIX occur?
In the early 1980s, the cloning of FVIII and FIX and subsequent expression of functional proteins occurred. This was during the “bad blood” era (when many individuals with hemophilia being treated with plasma-derived clotting factor were infected with HIV and/or HCV). This led to the development and commercialization of recombinant clotting factors. These initial products were manufactured using Chinese hamster ovary cells or baby mouse kidney cells. Manufacturers injected these cells with the factor gene so that large amounts of the factor protein could be produced. Since the proteins are extracted from animal cells, they are not at risk for containing human viruses. Some factor concentrate products are stabilized using human albumin, while others are stabilized using sucrose. This was life-changing for many with hemophilia, allowing for prophylactic (or preventive) treatment. Some companies are now using human embryonic kidney (HEK) cells to grow the factor.
What is a broviac catheter?
BROVIAC® catheters and HICKMAN® catheters (often referred to as “broviacs”) are similar to a PICC line. However, A BROVIAC® catheter is placed directly into a central vein and threaded to a position just above the heart. It is tunneled under the skin and brought out away from the site where it enters the vein to theoretically prevent bacteria from gaining access to the central portion of the catheter. BROVIAC® catheters contain a “cuff” that is under the skin. As the skin grows into this “cuff,” the catheter becomes more stable, reducing the chance of it becoming pulled out. Like the PICC line, his device is easy to use and does not require sticks into the person’s skin. The difference is that these catheters can last for a prolonged period of time. The most common long-term complications of this type of central line are infection, movement that takes the catheter out of the proper position, and damage to the catheter.
What is a butterfly needle used for?
Peripheral venous access, where a butterfly needle is inserted directly into a vein and is used to infuse FVIII into the bloodstream, is commonly used by those who infuse at home but do not have a venous access device , such as a port, PICC line, or BROVIAC®. Below are some considerations regarding this type of access:
What does it mean to be on FVIII?
Being on prophylaxis means infusing FVIII on a regular schedule to prevent bleeds from occurring. Prophylaxis is recommended for children with severe hemophilia, but it can also be recommended for those who have frequent bleeds. Prophylaxis may also be used in advance of activities that are likely to cause a bleed. There are two types of prophylaxis:
Can you infuse FVIII into bloodstream?
All FVIII products need to be infused directly into the bloodstream. There are several ways to infuse FVIII, and each has its advantages and disadvantages. These include peripheral infusion (accessing a vein with a butterfly needle), port-a-catheter (also called a port), a peripherally inserted central catheter (PICC) line, or a BROVIAC® or HICKMAN® catheter.
Does hemophilia have an inhibitor?
While anyone with a bleeding disorder can develop an inhibitor to clotting factor, those with hemophilia A develop inhibitors more often than the other bleeding disorders. Inhibitors are antibodies that the immune system develops because it perceives the infused FVIII as a foreign substance that needs to be destroyed. Antibodies are proteins that eat up the FVIII before it has time to stop the bleeding.
How is hemophilia managed?
In most cases a child with severe hemophilia is managed at home by his parents, with the administration of factor on a prophylactic schedule. As the child gets older, he is taught how to self-administer his factor on schedule or when an acute bleed occurs.
How to treat hemophilia in children?
If your child has hemophilia, make sure school and babysitters understand special needs. Keep a first aid kit with you at all times. Minor cuts can usually be treated with gauze, pressure, and bandages. Raise the affected part of the body.
What is hemophilia bleeding disorder?
Hemophilia, an inherited bleeding disorder, occurs when blood clotting factors are faulty or missing. It almost always affects males. Bleeding can happen both internally and externally.
Why does hemophilia occur?
The disorder occurs because certain blood clotting factors are missing or do not work properly. Because a clot does not form, extensive bleeding can be caused from a cut or wound.
What is the cause of hemophilia type B?
Type B hemophilia is caused by a deficiency of factor IX. This type is also called Christmas disease.
What is the chance that any of her sons will inherit the gene and be born with hemophilia?
There is a 50% chance that any of her sons will inherit the gene and will be born with hemophilia. There is also a 50% chance that any of her daughters will be carriers of the gene without having hemophilia themselves.
How many types of hemophilia are there?
There are two main types of inherited hemophilia:
How to treat bleeding disorders?
Treatment Options for Bleeding Disorders 1 Standard half-life therapies: Standard half-life therapies are used to treat hemophilia A and B, some types of von Willebrand disease, and some rare factor disorders. Dosing can be anywhere from three times a week to every day, depending on the person. 2 Extended half-life (EHL) therapies: EHL contains a molecule that has been modified in some way to delay the breaking down of factor in the body. This results in higher levels of factor in the body lasting for longer, resulting in less frequent infusions. How long the factor is effective in the body depends on the person. Extended half-life therapies are mostly used to treat hemophilia A and B. 3 Bypassing agents are used to treat bleeds in people with hemophilia with inhibitors. These treatments contain other factors that can stimulate the formation of a clot and stop bleeding.
What is EHL therapy?
Extended half-life (EHL) therapies: EHL contains a molecule that has been modified in some way to delay the breaking down of factor in the body. This results in higher levels of factor in the body lasting for longer, resulting in less frequent infusions. How long the factor is effective in the body depends on the person.
What is extended half life therapy?
Extended half-life therapies are mostly used to treat hemophilia A and B. Bypassing agents are used to treat bleeds in people with hemophilia with inhibitors. These treatments contain other factors that can stimulate the formation of a clot and stop bleeding.
Is emicizumab a vasopressin?
Emicizumab was approved by the FDA to treat people with hemophilia A with inhibitors in 2017 and for people with hemophilia A without inhibitors in 2018. Read MASAC's recommendation on emicizumab. Desmopressin (DDAVP) is the synthetic version of vasopressin, a natural antidiuretic hormone that helps stop bleeding.
What is the main aim of hemophilia treatment?
The main aim of hemophilia treatment is to prevent life-threatening bleeding and/or treat muscle and joint bleeding. Early, treatment was limited to on-demand therapy, ie, the infusion of concentrate after the occurrence of the bleeding, also allowing the home therapy a prompt and successful treatment.43
When was hemophilia first treated?
After assessing that hemophilia was due to the lack of a plasma clotting factor,9the disease’s first treatment was introduced in 1948 by the infusion of plasma from healthy blood donors.10In 1958, Nilsson 1M and Blomback B in Sweden successfully treated HA patients with a globulin fraction of human plasma purified by the Cohn’s fractionation method and contained in the fraction 1-0.11At about the same time, in 1964, a new era of hemophilia therapy started after the discovery of cryoprecipitate from the plasma of a single blood donor.12,13Unfortunately, cryoprecipitate’s specific activity was relatively low (FVIII:C 0.2 IU/mg/mL).13,14The need for production and storage at −20°C in plastic bags made this approach to hemophilia therapy cumbersome and inconvenient. Furthermore, each cryoprecipitate bag contained only about 100 IU of FVIIl. A hypothetical dose of 20–30 IU/kg required the administration of about 14 or 21 bags to a PWH of 70 kg body weight. The pharmaceutical industry soon began producing lyophilized FVIII concentrates, starting from a large pool of plasma. Again, the first step was the cryo-precipitation of the plasma, but purification methods allowed the production process to achieve a remarkably high specific activity, mainly through immunoaffinity chromatography with monoclonal antibodies specific for FVIll. Unfortunately, the concentrates from large plasma pools and the single donor cryoprecipitates were contaminated by the hepatitis viruses15even though the infection risk was lower for cryoprecipitates.16Later, HIV transmission occurred in 75% of HA patients treated with commercial clotting factor concentrates17but only in 20% of those treated with single donor cryoprecipitates,18possibly since the donors were known to the patient, typically a parent. HIV transmission occurred in more than 50% of the PWH in the United States;19In Italy, probably due to the large availability of the first Prothrombin Complex Concentrates,20the prevalence of HIV infection was 47.1% in people with hemophilia B but 26.8% among those with hemophilia A.21Before the end of the last millennium, three significant advances in the manufacturing process of concentrates impacted the viral safety of products used for replacement therapy:
How much factor should I use for hemophilia?
The observation that in hemophilia patients moderate (FVIII/IX: 1–5 IU/dL) or mild disease (FVIII/IX: 5–40 IU/dL), bleeding was uncommon or absent suggested that increasing the factor level with an adequate amount of FVIII/IX concentrate every two or three other days to maintain the FVIII/FIX plasma concentration above 1IU/dL might prevent bleeding. According to a study conducted in the Netherlands, only a baseline FVIII of at least 12 IU/dL was able to entirely abolish the risk of joint bleeding. Another study from the US examined data collected over an 11-year period from males with non-severe hemophilia A or B without inhibitors who were treated on-demand with factor therapy. These authors showed that levels of 20% may be required to prevent all joint bleeding.47Another study from the Netherlands showed that PWH who have a baseline factor activity of at least 5 IU/dL experience one episode of joint bleeding each year while those with a baseline level of 3 IU/dL experience two episodes yearly.48Unfortunately, even a single episode of joint bleeding may trigger hemophilia arthropathy.49
Where are recombinant FVIII concentrates produced?
The first-generation recombinant FVIII concentrates were produced in Chinese Hamster Ovary (CHO) cells, transfected with human cDNA encoding for FVIII in a culture medium containing human albumin.27,28To improve the purity of recombinant FVIll concentrates, albumin was removed from the culture media (second-generation rFVIII concentrates), and finally, albumin was eliminated from the final formulation and a non-protein stabilizer added prior to lyophilization (third-generation rFVIII).29Soon afterward the introduction of the first rFVIII concentrates, rFIX concentrate was also introduced for HB treatment.30At about the same time, a modified rFVIII molecule, in which the B domain had been deleted31or truncated was marketed and showed improved production yield from the cell line and, in the following years, became the standard procedure to produce rFVIII concentrates.32Unfortunately, after the widespread conversion from plasma-derived FVIII (pdFVIII) to rFVIII concentrates for the therapy of HA, the incidence of neutralizing antibodies directed to the clotting activity of FVIII, so-called “inhibitors” became more evident. This adverse event is very severe because the effect of the infused products can be entirely or partially reduced, according to the titer of inhibitor. The incidence of inhibitors is 24% in HA patients treated with pdFVIII concentrates but 33% and up to 52%33–35of those treated with rFVIII concentrates, depending on the study. The high incidence of inhibitors against rFVIII in previously untreated patients (PUPs) was also observed in the regulatory clinical trials for approval of all rFVIII concentrates: the incidence was 29.7% for Kogenate®(Bayer), 31.0% for Recombinate®(Baxter), 33.0% for ReFacto®(Pfizer), and 38.0% after the first 18 exposure days to Kogenate®.36,37The claimed lower immunogenicity of pdFVIII versus rFVIII concentrates was contradicted by a prospective study of PUPs conducted in Germany in which no difference between pdFVIll (36%) and rFVIll (36%) concentrates was observed.38Other retrospective or observational studies showed discordant results between pdFVIII and rFVIII. A randomized, controlled, open-labeled trial in PUPs with severe hemophilia A (Survey of Inhibitors in Plasma-Product Exposed Toddlers [SIPPET]) was conducted in Europe, Asia and the US in which the incidence of inhibitors after the first exposures to pdFVIII or rFVIII concentrates was compared.39The cumulative incidence of FVIII inhibitors observed in 29 HA patients treated with pdFVIII was 26.8% vs 44.5% in 47 HA treated with rFVIII concentrates, respectively. The hazard ratio of developing inhibitors was 1.87 (95% Cl: 1.17–2.96) for rFVIII vs pdFVIII concentrates. Similar outcomes were observed from a study conducted in France.40In conclusion, the immunogenicity of both pdFVIII and rFVIII remains a significant, unsolved adverse event of replacement therapy of HA. After treating HB with pdFIX or rFIX concentrates, FIX inhibitors’ incidence is exceptionally low, about 3%.41These antibodies can fix the complement, and, in some patients, severe anaphylactic reactions occurred just after the intravenous (iv) infusion of the concentrate.42
How often should I give a FVIII?
The prominent feature limiting the benefit of prophylaxis has been the need for frequent, repeated iv infusions every 2–3 days for FVIII and every 5–7 days for FIX concentrates, respectively. The pharmaceutical industry has developed some biochemical methods to increase the HL of concentrates in an effort to reduce the burden of the treatment on patients, especially for young patients. The ability to prolong the plasma half-life and extend the interval between injections followed the application of methods to conjugate the factor molecule with the fragment crystallizable (Fc) of IgG1 or albumin or by adding polyethylene glycol (PEG), which has led to a significant extension of the half-life of concentrates, especially for rFIX. Modifications were first applied to rFIX:
Why is it important to prevent bleeding with replacement therapy?
The aim of replacement therapy is to prevent fatal bleeding and the effects of bleeding on the joints and muscles . Some patients can recognize the symptoms forecasting the bleeding, the so-called “aura.” However, prevention of bleeding is better than treating bleeding with on-demand replacement therapy because, in the short-run, joint inflammation leads to new bleeding and starts a vicious circle that ends in severe arthropathy . Therefore, prevention of bleeding, so-called prophylaxis, was hypothesized to result in better outcomes than on-demand therapy, especially if a minimum trough level was maintained in the plasma. Maintaining the trough level of FVIII or FIX above 3–5 IU/dL is sufficient to reduce the number of bleeding events to one or two episodes every year.48
What is the name of the procedure that extends the HL?
pegylation, the linkage of the molecule with PEG (Rebinyn/Refixia®, Novo Nordisk), which had been a successful procedure for many other drugs to extend their HL;
What is the purpose of a lab test for hemophilia?
These tests help doctors diagnose the type of hemophilia and its severity.
What are the complications of hemophilia?
Complications from treatment for hemophilia include: 1 Acquiring a blood-borne disease 2 Changes to the immune system that make the treatment less effective
What is emicizumab KXWH?
Emicizumab -kxwh (HEMLIBRA) is a medicine that can help prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A. It works by bridging the gap in the clotting factors left by the missing factor VIII. This medication is given as a weekly, under-the-skin (subcutaneous) injection.
What is the plug in the blood called?
Normally, when bleeding begins, a complex series of chemical events produces a "plug" to stop the bleeding; this plug is called a fibrin clot. The fibrin clot is the end-product of many different "clotting factors" reacting in the blood. Hemophilia is an inherited condition in which one of these clotting factors (mainly factor VIII or IX) ...
How to treat a bleed in a joint?
For bleeding joints, you must get treatment with clotting factor to avoid joint damage. Your doctor may also recommend resting and icing the affected joint to decrease pain and swelling. As pain and swelling subsides, physical therapy may help you recover joint mobility and strength.
Why is it important to donate blood?
Still, if you have hemophilia it is important for you to receive immunizations for hepatitis A and B to help prevent becoming infected with these viruses.
Do clotting factors have to be used as often?
Newer types of these clotting factor products have been developed so they can last longer in the body. This means that they do not have to be used as often. Other medicines have also been developed to work with the clotting factors to stop bleeding.
What is hemophilia clotting?
Table of Contents. Hemophilia is usually an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery. Blood contains many proteins called clotting factors that can help to stop bleeding. People with hemophilia have low levels ...
How is hemophilia determined?
The severity of hemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems. In rare cases, a person can develop hemophilia later in life. The majority of cases involve middle-aged or elderly people, ...
What is the effect of hemophilia on blood clotting?
About 15-20 percent of people with hemophilia develop an antibody (called an inhibitor) that stops the clotting factors from being able to clot the blood and stop bleeding. Treatment of bleeding episodes becomes extremely difficult, and the cost of care for a person with an inhibitor can skyrocket because more clotting factor or a different type of clotting factor is needed. People with inhibitors often experience more joint disease and other problems from bleeding that result in a reduced quality of life.
What tests are done to determine if a newborn has hemophilia?
To make a diagnosis, doctors would perform certain blood tests to show if the blood is clotting properly. If it does not, then they would do clotting factor tests, also called factor assays, to diagnose the cause of the bleeding disorder.
How do you know if you have hemophilia?
Signs and Symptoms. Common signs of hemophilia include: Bleeding into the joints. This can cause swelling and pain or tightness in the joints; it often affects the knees, elbows, and ankles. Bleeding into the skin (which is bruising) or muscle and soft tissue causing a build-up of blood in the area (called a hematoma).
Does hemophilia run in families?
Even though hemophilia runs in families, some families have no prior history of family members with hemophilia. Sometimes, there are carrier females in the family, but no affected boys, just by chance.
Can you get hemophilia later in life?
In rare cases, a person can develop hemophilia later in life. The majority of cases involve middle-aged or elderly people, or young women who have recently given birth or are in the later stages of pregnancy. This condition often resolves with appropriate treatment.
What are vectors used for hemophilia?
The most commonly used vectors in hemophilia are called adeno-associated viruses, or AAV. These vectors do not carry any infectious material, meaning they do not cause viral infections. They are used to deliver working genes into liver cells in the body so that they can start producing clotting factor.
Where does a working gene go in hemophilia?
In gene therapy, a working gene is carried into the liver cells of a person with hemophilia. Once the working gene reaches the cells, they should begin producing factor.
Why are vectors used in gene therapy?
It is used as a carrier to bring the new, working genes into a person’s cells. Viral vectors are used in gene therapy because they are very effective at getting into cells.
Why do we do clinical trials?
Clinical trials are done to ensure that gene therapy, or any other treatment is safe and effective, and durable. Clinical trials for hemophilia A gene therapy are underway and could be submitted to the Food and Drug Administration (FDA) for approval in the next few years.
Does gene therapy help hemophilia?
Gene therapy for hemophilia targets the liver cells. Children’s livers continue to grow until, at least, age 12. As the liver grows, the effects of gene therapy reduces. As we learn more about gene therapy safety, there may be opportunities for enrollment of children.
Can hemophilia cause higher factor levels?
Current studies have shown that patients with hemophilia who undergo gene therapy may see their factor levels increase – sometimes to normal levels. They may also be able to avoid some factor infusions for a long period of time. However, studies are still ongoing to determine how long these benefits will last. As with many other treatments and medications, each patient that receives gene therapy may have different results, meaning some patients may reach higher factor levels than others.
Is hemophilia male or female?
Often, we think of hemophilia [as] associated with males. In other words, there are many more males that have hemophilia than females. And the genetic basis of this... In order to understand that genetic basis is to understand the basis of gender as it's coded in our genome.
Is hemophilia an inherited disease?
Narration. Hemophilia is an inherited disease that's characterized by bleeding beyond what would be expected in a normal individual. In other words, they have a deficiency in the ability to clot their blood. Often, we think of hemophilia [as] associated with males.