health canada-approved treatments: hemophilia
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factor replacement therapy (frt) is a preventive infusion medication injected directly into the bloodstream by a healthcare provider.
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this article is for informational purposes only and is not intended to provide medical advice, diagnosis or treatment. always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.
hemophilia is a rare, often inherited disorder that affects blood clotting. typically, if a person experiences bleeding within or outside the body, blood clots at the site to prevent too much blood loss.
in people with hemophilia, the blood cannot clot as it should, leading to more prolonged bleeding. those with hemophilia don’t usually have to worry about minor cuts but rather internal bleeding, which is more of a concern in people with severe forms of the condition.
internal bleeding in hemophilia can occur in the joints or brain and can damage tissues or, in the worst case, cause death.
there are four types of hemophilia:
- hemophilia a: caused by a deficiency of clotting factor 8.
- hemophilia b: caused by a deficiency of clotting factor 9.
- hemophilia c: caused by a deficiency of clotting factor 11.
- acquired hemophilia: immune system attacks healthy clotting factors.
hemophilia a, b, and c are caused by genetic mutations that hinder the body’s ability to create clotting factors, proteins that help blood clot. these proteins work with blood cells known as platelets to keep blood from flowing too freely during a bleed. people with hemophilia lack an adequate amount of clotting factors.
acquired hemophilia occurs when the immune system mistakes healthy clotting factors for pathogens and attacks them, damaging them to the point where they can no longer perform the actions needed to clot the blood.
symptoms of hemophilia include:
- spontaneous bleeding
- large or deep bruises
- joint pain and tightness
- blood in urine or stool
- unexplained nosebleeds
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because of these spontaneous bleeds, people living with hemophilia are at risk of adverse complications, such as internal bleeding that damages tissues, bleeding in the brain, throat, or neck, joint damage, and infection.
in many cases, people will be diagnosed with hemophilia during infancy or childhood, but mild cases can take until adulthood to be diagnosed. since the complications of hemophilia can be life-threatening, it is vital to get a proper diagnosis and treatment for the disorder as soon as possible.
this article explores all the treatment options available for canadians living with hemophilia.
prescription medications
prescription medications can be effective therapies for people with hemophilia, and there are many options to choose from. each type is geared toward an individual’s needs, specific type and severity, and what works best for them.
factor replacement therapy
factor replacement therapy (frt) is a standard treatment for people with mild forms of hemophilia a or b. it is considered the “gold-standard” therapy for those with hemophilia a, specifically.
frt is a preventive infusion medication injected directly into the bloodstream by a healthcare provider. the infusion typically takes five to ten minutes, and people can request to get it at home or in the clinic.
frt works by introducing more clotting factors into the body so that a person has enough to clot properly. there are two sources of clotting factors for people with hemophilia. they include:
- plasma extracted from human blood
- cloned clotting factors that are created using dna technology
following the procedure, the clotting factor numbers return to that of a person without hemophilia. however, if a person gets a standard half-life infusion, this treatment does not last longer than three days, and people will have to continually get the infusions to ensure that their blood clotting factors remain high enough to avoid bleeding.
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a new set of clotting factor concentrates were introduced in canada in 2016. they have an extended half-life, so people who use these concentrates will have protection against bleeds for up to 100 hours, depending on the type of clotting factor being replaced.
this type of therapy comes with potential complications, such as the immune system’s development of antibodies or inhibitors. these antibodies bind to the newly introduced clotting factors, rendering them less potent and, in turn, reducing treatment efficacy.
roughly 20 to 30 per cent of people with hemophilia a who get frt will develop inhibitors. those numbers are significantly lower in those with hemophilia b at approximately 3 to 5 per cent. once patients develop inhibitors, they can no longer receive in frt for hemophilia management.
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non-factor replacement therapy
non-factor replacement therapy is another preventive therapy that uses molecules specifically engineered to perform the task of clotting factors without introducing new clotting factors into the blood. there are several currently available in canada, including:
- emicizumab
- concizumab
- kovaltry
- yntha
- zonovate
- adynovate
- eloctate
- esperoct
- jivi
- benefix (quebec only)
- rixubis (quebec only)
- alprolix
- idelvion
- rebinyn
emicizumab is used to treat hemophilia a. the medication contains a bispecific monoclonal antibody, a protein that can bind to clotting factors in the blood to mimic their function and improve blood clotting. this leads to lower instances of spontaneous bleeding.
it is a subcutaneously medicine which is injected underneath all the layers of the skin at various dosing intervals. some people may need once-weekly injections, while others may have to inject themselves with the medication once every two or four weeks.
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emicizumab can also be used during active bleeding episodes, but it is intravenously infused when used in this way. this drug can be used by people with hemophilia a, with or without inhibitors.
people taking this medication may be at risk of complications if they also receive another type of medication known as activated prothrombin complex concentrate (feiba). simulatenous use of these two medications can cause the formation of blood clots in the veins, capillaries, and small arteries that can travel throughout the body causing life-threatening adverse events.
feibas are bypassing agents used when a person develops inhibitors against factor medication. because of this, feibas should be avoided in people who have developed inhibitors while on emicizumab.
while emicizumab is considered safe, people may experience side effects, such as a reaction at the injection site, joint pain, headaches, fever, or diarrhea. these are generally mild, but other serious side effects can occur, including:
- pain in the stomach, chest, eyes, and back
- swelling in the arms, legs, or eyes
- feeling sick, faint, numbness in the face, weakness, or confusion
- experiencing shortness of breath, coughing up blood, a fast heart rate, or nausea and vomiting
- yellowing of the skin and eyes
- difficulty seeing
- a reduction in urine output
these symptoms require medical care and, if experienced, should prompt you to call your doctor. people who are pregnant, breastfeeding, or planning to become pregnant should let their doctors know prior to starting emicizumab.
concizumab is another non-factor replacement therapy option. it is a monoclonal antibody that works by targeting tissue factor pathway inhibitors (tfpis), which are proteins that lower the rate of clotting. when this is introduced into the body, it restores balance in clotting proteins to improve how the blood clots during bleeding in people with hemophilia.
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it is also administered subcutaneously, once daily, and can be used as a treatment for people with hemophilia a and b with inhibitors. feibas should be avoided during therapy with concizumab unless otherwise directed by your doctor because the way they are taken changes after starting this medication.
there are several potential side effects associated with this drug. they include:
- an increased risk for blood clot formation (which can be life-threatening)
- allergic reaction
- injection site reactions
- infections
- headaches
- joint stiffness
- fever
- immunogenicity (the body creating anti-drug antibodies that hinder the drug’s ability to perform its task)
those who are allergic to the active substance or ingredients of concizumab should avoid the medication. it should also be avoided in people who are younger than 12 and those who are pregnant, breastfeeding, or planning to become pregnant.
since blood clots can be severe and life-threatening and can occur while taking both emicizumab and concizumab, it’s essential to understand the signs. potential signs of a blood clot include:
- swelling, pain, or tenderness in one or both legs or arms
- sudden and unexplained pain in the chest, stomach, and upper or lower back
- shortness of breath or difficulty breathing
these symptoms require immediate medical care.
as mentioned above, the other brand names work similarly to emicizumab and eoncizumab and pose the same risks and complications. some are approved for use in hemophilia a, whereas others are approved for hemophilia b.
those approved for hemophilia a include:
- kovaltry
- xyntha
- zonovate
- adynovate
- eloctate
- esperoct
- jivi
those approved for use in hemophilia b include:
- benefix (quebec only)
- rixubis (quebec only)
- alprolix
- idelvion
- rebinyn
each of these drugs will provide protection against bleeds or help to stop bleeding in people living with hemophilia a or b.
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the difference between some of these medications is their half-life or the time it takes for the body to reduce the amount of drug in the system by half. for hemophilia a, kovaltry, xyntha, and zenovate all have the same standard half-life of roughly 14.2 hours. adynovate, eloctate, esperoct, and jivi all have an extended half-life of roughly 18 to 19 hours.
in the drugs used for hemophilia b, benefix and rixubis have a standard half-life, and aprolix, idelvion, and rebinyn have an extended half-life.
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desmopressin
desmopressin is a clotting medication used by people with mild hemophilia a. it works by encouraging the release of clotting factors in the body to help restore levels and reduce the risk of spontaneous bleeds.
the use of desmopressin is localized to instances where a person with hemophilia is expecting to bleed, so it can be used to control or prevent bleeding. for example, people visiting the dentist may expect to bleed, and taking desmopressin 30 to 60 minutes before the appointment time can help prevent that.
in other instances where bleeding may need to be controlled, desmopressin can be taken in the 24 to 48 hours prior so that the body has time to restore levels of clotting factors in a way that controls bleeding adequately.
there are three administration methods for desmopressin: intravenously into a vein, subcutaneously, and sprayed into the nose. within an hour, the medication takes effect and continues to work for up to 12 hours.
several side effects are associated with desmopressin, the most common being temporary flushing in the face. others can include:
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- headaches, dizziness, and stomach pain
- changes in blood pressure or pulse
- a reduction in urine output
- diarrhea, nausea, vomiting, weight gain, or loss of appetite
- cognitive changes, such as abnormal thinking, irritability, confusion, slowed reflexes, extreme tiredness, or hallucinations
- loss of consciousness or seizures
- headaches
- restlessness
- muscle weakness, spasms, or cramps
if someone taking desmopressin has a very severe headache or has not been able to urinate for over 24 hours, they will need emergency medical attention.
older adults over the age of 65 should avoid taking desmopressin, and people should speak to their doctor prior to starting the medication if:
- they are pregnant, breastfeeding, or plan to become pregnant
- have high blood pressure, conditions that cause extreme thirst, cystic fibrosis, or heart disease
- have kidney disease or low sodium levels
desmopressin may interact with some medications or alcohol, so it’s best to speak to your doctor about any other drugs or supplements you are on, as well as your alcohol intake before you start taking it.
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gene therapy
gene therapy is a relatively new approach to hemophilia treatment. it is a one-time therapy that drives the person’s body to create blood clotting factors to improve their symptoms. while promising, these types of drugs are not a cure for hemophilia and do not work for everyone. that said, gene therapy does have the potential to provide longer-lasting results when compared to other treatments.
gene therapy can be used for people living with hemophilia a or b, though only two have been approved in canada for hemohphilia b:
as of writing, two gene therapy drugs are approved in canada:
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- beqvez
- hemgenix
that said, these drugs have not yet been reimbursed or marketed in canada.
gene therapy works by modifying genes in people with hemophilia to correct the issue that causes clotting factors to be absent or not work as they should.
a process known as gene transfer is used, which introduces a modified version of an adeno-associated virus into the body alongside a working copy of the gene that drives the production of clotting factors. the virus delivers the gene to where it needs to be in the body, encouraging a correction and the normal production of clotting factors.
this therapy can only be done once, as the body’s immune system sees the virus as a threat and creates antibodies against it after it is encountered.
people who may be approved for gene therapy include:
- those living with severe hemophilia a who are over 18 and have no history of inhibitors developing or liver disease
- those living with moderate-to-severe hemophilia b who are over 18 and have no history of inhibitors
the most notable complication of gene therapy for hemophilia is liver inflammation. because of this, most people who go this route will have to use corticosteroids after getting gene therapy, which come with their own side effects, including:
- pain and muscle cramps
- changes in mood, such as depression, mood swings, and agitation
- vision issues
- unusual weight gain
- swelling in the hands, ankles, feet, and a puffy face
- signs of infection, such as a sort throat or fever
- stomach bleeding that can present as abdominal pain, vomit that looks like coffee grounds, and black or tarry stools
- weakness, slow wound healing, thinning skin, and easy bruising or bleeding
- changes to the menstrual period
- irregular heartbeat
- seizures
after undergoing gene therapy, a person’s cancer risk may also increase. since gene therapy is new, the data surrounding its long-term safety is unavailable. speaking to a healthcare provider about the benefits and risks associated with gene therapy is the best way to decide if it’s right for you.
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tranexamic acid and aminocaproic acid
tranexamic acid and aminocaproic acid are oral medications designed to stop a specific enzyme from dissolving blood clots. they work by encouraging blood clots to remain intact and in place to prevent bleeds. they are used alongside other medications that help the blood clot to form.
they are used to hold blood clots in place in various areas of the body, including:
- inside the mouth and nose
- within the intestines
- inside the uterus
they are typically used to manage bleeding related to dental procedures, intestinal bleeding, and heavy and prolonged menstrual bleeding.
while these drugs are generally safe, they do come with various mild side effects, including:
- headaches, fatigue, or dizziness
- upset stomach or nausea
- diarrhea or loose stools
- stomach pain
the use of alcohol or cannabis while on these drugs can make side effects worse, especially dizziness. once the drugs are stopped or the dosage reduced, the side effects dissipate.
these drugs may not be suitable for everyone and should be avoided in people with:
- allergies to the drug
- a history of blood clots deep in the veins or the lungs
- coagulopathy
- epilepsy
- kidney problems
- pregnant or trying to become pregnant
- irregular periods
your doctor will speak to you about other medications or supplements you are on before prescribing these medications to ensure that no reaction takes place.
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over-the-counter options
there are no over-the-counter options available to treat or prevent bleeds in people living with hemophilia. however, since the condition can cause chronic pain, using an over-the-counter pain reliever can help.
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acetaminophen
acetaminophen is the number one recommended pain reliever for people living with chronic pain caused by hemophilia because they cannot take nsaids, such as aspirin, aleve, advil, motrin, or other medicines that contain the ingredient salicylate. because of the risk these drugs pose for bleeding, they should be avoided in people living with hemophilia.
there are various name brands of acetaminophen, the most notable being tylenol, but excedrin is a popular choice as well. over 400 brands of acetaminophen are available in canada.
to use acetaminophen safely, it’s important to follow the dosing schedule exactly. adults and children over the age of 12 should not exceed 4,000 mg in a day, which equates to 8 extra-strength pills or 12 regular-strength pills over a 24-hour period.
children under the age of 12 are given acetaminophen doses based on their weight and age, and instructions are included in all children’s acetaminophen products.
while acetaminophen is generally considered safe, people with liver disease or alcoholism should avoid it or use less than the recommended dose if given the go-ahead from a doctor because if the liver doesn’t adequately process the drug, it can build up and become toxic. this is known as drug-induced hepatitis.
the risk of overdose is low but not non-existent. if a person takes too much acetaminophen in a short period of time, they can develop acute liver failure or other liver injuries that could lead to the need for a liver transplant or death.
symptoms of an acetaminophen overdose can include:
- nausea
- vomiting
- loss of appetite
- sweating
- stomach or abdominal pain
- extreme tiredness
- yellowing of the skin or eyes
- dark urine
these symptoms should not be ignored and require medical attention.
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treating hemophilia in canada
many treatments are available for hemophilia in canada, and each one will be recommended based on a person’s unique presentation of the disease and what they need most.
living with hemophilia can be difficult because of the risk of life-threatening bleeds, so it’s crucial to follow all treatment plans given by your doctor exactly as they advise. that way, you can prevent the worst from happening and reduce the number of bleeds experienced.
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