Understanding your treatment

Understanding your treatment

Why do I need treatment?


When a person living with haemophilia has a bleed, it takes longer than normal for the bleeding to stop. This is because the body isn't producing enough of the protein that helps the blood clot (and stop the bleeding). For the clotting process, blood platelets along with special proteins, called clotting factors, help form the clot, which is necessary to stop the bleeding and protect the body while it heals. The most common way to treat haemophilia is to replace the missing clotting factor so that the blood can clot properly.

 

Bleeds and what they do


Without proper care and treatment, haemophilia can result in bleeding within the joints and muscles. This bleeding can lead to chronic joint disease and; bleeding in the head (and sometimes in the brain ) which can cause long-term problems, such as seizures and paralysis; and, if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain, even death. Most often, bleeding occurs internally in the joints (an area where two bones come together) or muscles, and the severity of symptoms may depend on how low the level of clotting factors in the blood. The joints that are most often affected are the knee, ankle and elbow. Repeated bleeding without prompt treatment can damage the cartilage and the bone in a joint, which may lead to chronic arthritis and disability. This is one of the reasons it is important to have a haemophilia treatment plan in place.1

So to sum up, as all bleeds can be potentially dangerous. The goal with haemophilia treatment is to decrease the frequency and severity of bleeding episodes to limit the damage they can cause to your body.

 

The human body has six main joint types
- keep all of yours active to maintain their functionality.

six main joint types

Why every bleed matters


Joint disease is a complication of haemophilia, so it is important to try to prevent bleeding in order to protect your joints for the future. Joint damage can occur after repeated bleeding into the same joint, or even after only one serious joint bleed. In an ideal world, the advice would be to avoid bleeds altogether - but in the real world, they happen. If you do get one, treating it at the very first sign is crucial because an affected joint will be more likely to bleed again, starting a vicious cycle which could potentially lead to long-long term joint damage2.

Choose the treatment that's right for you


Just as haemophilia affects everyone differently, your treatment can be personalised to fit your individual lifestyle - because after-all no two people are the same. That's why it’s important to understand how haemophilia affects your body throughout the course of the day or any given activity. That way you, together with your haemophilia care team, can decide on the treatment plan that lets you feel safe, comfortable and confident that you have the protection you need for whatever you choose to do and wherever you choose to go in life!

One size does not fit all


Everyone needs different protection for various stages of life and for different actives.

one size doesn't fit all

Everyone in life, haemophilia or not, faces different challenges (and opportunities) as we age. If you are living with haemophilia, it's important to have a personalised treatment plan that protects you and helps you to feel safe so you can get on living your life to the full.

For example, when children living with haemophilia are growing up and playing with their friends, they might need to take slightly higher doses of their treatment at shorter intervals.

Or if you are an adult living with haemophilia and require surgery, your doctor will adjust your factor levels so that clotting works as it should during the surgery and through the healing process.

Likewise, if it's summer and you're off to hike up a mountain, you might be advised to take your treatment at shorter intervals on those more active days. But if you're headed to the beach to read a couple of books you might want to increase the intervals between treatments during those lazy days in the sun.

From these examples you can see how a treatment plan can be personalised to fit you and your individual needs - whatever they are - so that you can work towards your goals without haemophilia getting in the way.

Treatment possibilities

Of the haemophilia treatment options available, factor replacement therapy is the most common. It's a good idea to understand the different treatment options before talking to your doctor about which treatment is suited to your needs.

An introduction to factor replacement therapy


The main treatment for haemophilia is called factor replacement therapy and it works just like it sounds: it replaces the clotting factor (factor VIII (8) for haemophilia A, and factor IX (9) for haemophilia B) that your body doesn’t make or have enough of. This is done intravenously which means through a needle into a vein. Clotting factor products can either come from donated blood plasma or be recombinant, meaning they are made in a laboratory.

The World Federation of Heamophilia guidelines recommends that prophylaxis is used to prevent bleeding and joint destruction and it should be the goal of therapy to preserve normal musculoskeletal function. Prophylaxis decreases the number of bleeding episodes and may protect against joint disease and disruptions to quality of life. Traditionally, standard half-life (SHL) products have been used in replacement therapy. SHL is factor that lasts in the body for the same amount of time as the natural factor VIII, or factor IX. How often you need prophylaxis with SHL products depends on your personal needs and how you go about life, but people with haemophilia A usually need treatment three times a week and people with haemophilia B, twice a week3,4.

Not everyone with haemophilia chooses to, receive preventative treatment. Some people who could potentially be on prophylaxsis choose instead to get factor injections only when they bleed. Opting for on-demand treatments like this may be a personal choice but you should be aware that it could put you at higher risk of bleed-related joint damage.

 

What's 'half-life'?

 

You've probably heard a lot about "factor half-life" – but maybe you're not exactly sure what it is?

Basically, half-lite is the term for the amount of time the body takes to reduce the clotting factor to half in the bloodstream. Watch the film below! For a thorough explanation of the role of clotting factors and how there can a different half-life in each person.

Extended Half-Life (EHL) Factor


A newer type of factor replacement is called extended half-life (EHL) factor. This can last longer in the blood stream than standard factor, so many people on prophylaxis need treatment less often. For example, with haemophilia A, you may only need treatment twice a week instead of 3 times a week.27 For haemophilia B treatment may be weekly or even once a fortnight.28 Treatment for bleeds can be quicker too, with control after a single injection of EHL factor.5,6,7

There are currently three ways of producing EHL factor replacement: Fc fusion, PEGylation and albumin fusion. All of these techniques aim to prolong the half -life of clotting factors Vlll and IX by altering the structure of the protein molecules.   It might sound very scientific. but it basically means the body takes longer to remove protein from the blood so the clotting factor can work for longer and more efficiently after being injected7.

Bypassing and mimicking treatments

 

Some people with haemophilia A may stop responding to treatment. This is usually because they have developed antibodies, called inhibitors, against the clotting factors that are used to treat their haemophilia. Their body has simply started mistaking the replacement clotting factor as foreign invaders, and works to neutralise them. For these people, controlling a bleeding episode can be very difficult. But there is a way around this problem: instead of replacing the missing factor, special blood products called 'bypassing agents7 can be used to work around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. Bypassing agents are also licensed for non-inhibitor patients with haemophilia A.  

With mimicking treatment, an antibody mimics the function of factor VIII, rather than replacing the missing clotting factor VIII directly.

 

Other haemophilia therapies

 

  • Desmopressin (DDAVP). In cases of mild haemophilia, this synthetic hormone works by raising the levels of factor VIII in the blood. It can be injected slowly into a vien or provided as a nasal spray.
  • Clot-preserving medications (antifibrinolytics). These medications help prevent clots from breaking down.
  • Fibrin sealants. These medications can be applied directly to wound sites to promote clotting and healing. Fibrin sealants are especially useful in dental therapy.
  • Vaccinations. Factor replacement therapy that comes from human blood is routinely screened for viruses such as hepatitis and HIV. However, there is still a very small risk of contracting a disease from any blood product. If you have haemophilia it is important to be up to date on available vaccinations, including vaccines for hepatitis A and B.
  • Pain management Acute and chronic pain is unfortunately common for people living with haemophilia. The most effective way to help manage pain in haemophilia is to prevent bleeds, something which in turn can prevent repeated joint damage, a common source of chronic pain.
  • Physical therapy.This type of therapy can ease signs and symptoms if internal bleeding has damaged your joints.

 

Future Therapies


With gene therapy, researchers are trying to find ways to insert better functioning factor VIII or factor IX genes into the cells of people with haemophilia so their blood will clot more effectively. This method is not yet available and researchers are continuing to test it in clinical trials8.

 

What side effects are possible?


With any medicines, side effects are possible, although not everyone will experience these.
By reporting side effects, you can help provide more information on the safety of medicines. If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly via:

United Kingdom: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard
Ireland: HPRA Pharmacovigilance, website: www.hpra.ie; e-mail: medsafety@hpra.ie

You're in charge!

It’s totally normal- and usually encouraged - for you to self-treat if you have moderate or severe haemophilia. Although parents handle treatment and give intravenous injections for babies and small children, it is encouraged that children start to learn to do it themselves, which can create a sense of independence and confidence10. If you self-treat you’ll be free to enjoy your life without the worry of having to be close to your parent or carer in order to receive treatment.You can work with your haemophilia team to work out the best time to take your treatments to suit your lifestyle.

CARING FOR YOURSELF


With modern treatments your options are greater than ever before. However, despite great medical progress, as a person living with haemophilia. you will still need life-long treatment - whether it is prophylaxis or on demand injections.10 Having factor on hand is important because you never know when a bleed might occur and prompt treatment is important. So, whatever it is you are up to, be sure to keep your clotting factor with you - no matter if you are at home, being active or on vacation.

Yes, everybody’s treatment will be different, but being properly prepared and understanding how your factor levels are affected by your lifestyle is really important for everyone living with haemophilia. Learning to self-treat and being comfortable and confident in caring for yourself will help you feel liberated, so you can live life to the full and reduce the worry that today’s activities will limit tomorrow’s abilities.

FAQ - The fundamentals of haemophilia treatment

FAQ - New developments in haemophilia

Did you know that changing treatment is an option?

Make the most of your doctor's visit

REFERENCES

  1. Frequently asked questions.  World Federation of Hemophilia. https://elearning.wfh.org/elearning-centres/introduction-to-hemophilia.#hemophilia_faq. Last updated May 2012. Accessed November 2019
  2. Joint Damage. Hemophilla Federation of America. https://www.hemophiliafed.org/understanding-bleeding-disorders/complications/joint-damage/  Last updated N/A  Accessed June 2019.
  3. Haemophilia (Management: Approach). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/management-approach. Last updated April 2017. Accessed June 2019
  4. Haemophilia. BMJ Best Practice.  https://bestpractice.bmj.com/topics/en-gb/468/prevention. Last u dated April 2017.Accessed June2019
  5. Mahlangu J, Powell JS, Ragni MV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 2014, vol 123, issue 3, pp317-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894491/
  6. Santagostino E, Martinowitx U, Lissitchkov T et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825413 Accessed December 2019
  7. Alfonso Iorio et al (2016): Continuous prophylaxis with recombinant factor IX Fc Fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption. Journal of Medical Economics DOl:10.0180/13696998.2106.1265973
  8. Santagostin oE ,Martinwitx U  Lissitchltov T et al  Long-acting recombinant coagulation factor IX albumin fusion protein (rlX-FP )in hemophilia B:results lf a phase 3 trial. BLOOD April 2016.127(14). pp1761-9. In https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825413/ Accessed December 2019
  9. Clinical Commissioning Policy Emicizumab as prophylaxsis in people with congenital haemophilia A with factor VIII inhibitors (all ages) NHS England. https://www.england.nhs.uk/wp-content/uploads/2018/07/1717-emicizumab.pdf.  Published Jul 2018. Accessed 22nd August 2018
  10. Irish Haemophilia Society. Self-infusion. https://haemophilia.ie/living-with-haemophilia/parents/self-infusion .Accessed December 2019
  11. Guidelines for the Management of Hemophile (General care and management of Hemophilia: 1.6Prophylactic factor replacement therapy. World Federation of Hemophilia. https://www1.wfh.org/publications/files/pdf-1472.pdf   Last updated April 2013. Accessed December 2019

NP-9071
December 2019

Understanding your treatment

Why do I need treatment?


When a person living with haemophilia has a bleed, it takes longer than normal for the bleeding to stop. This is because the body isn't producing enough of the protein that helps the blood clot (and stop the bleeding). For the clotting process, blood platelets along with special proteins, called clotting factors, help form the clot, which is necessary to stop the bleeding and protect the body while it heals. The most common way to treat haemophilia is to replace the missing clotting factor so that the blood can clot properly.

 

Bleeds and what they do


Without proper care and treatment, haemophilia can result in bleeding within the joints and muscles. This bleeding can lead to chronic joint disease and; bleeding in the head (and sometimes in the brain ) which can cause long-term problems, such as seizures and paralysis; and, if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain, even death. Most often, bleeding occurs internally in the joints (an area where two bones come together) or muscles, and the severity of symptoms may depend on how low the level of clotting factors in the blood. The joints that are most often affected are the knee, ankle and elbow. Repeated bleeding without prompt treatment can damage the cartilage and the bone in a joint, which may lead to chronic arthritis and disability. This is one of the reasons it is important to have a haemophilia treatment plan in place.1

So to sum up, as all bleeds can be potentially dangerous. The goal with haemophilia treatment is to decrease the frequency and severity of bleeding episodes to limit the damage they can cause to your body.

 

The human body has six main joint types
- keep all of yours active to maintain their functionality.

six main joint types

Why every bleed matters


Joint disease is a complication of haemophilia, so it is important to try to prevent bleeding in order to protect your joints for the future. Joint damage can occur after repeated bleeding into the same joint, or even after only one serious joint bleed. In an ideal world, the advice would be to avoid bleeds altogether - but in the real world, they happen. If you do get one, treating it at the very first sign is crucial because an affected joint will be more likely to bleed again, starting a vicious cycle which could potentially lead to long-long term joint damage2.

Choose the treatment that's right for you


Just as haemophilia affects everyone differently, your treatment can be personalised to fit your individual lifestyle - because after-all no two people are the same. That's why it’s important to understand how haemophilia affects your body throughout the course of the day or any given activity. That way you, together with your haemophilia care team, can decide on the treatment plan that lets you feel safe, comfortable and confident that you have the protection you need for whatever you choose to do and wherever you choose to go in life!

One size does not fit all


Everyone needs different protection for various stages of life and for different actives.

one size doesn't fit all

Everyone in life, haemophilia or not, faces different challenges (and opportunities) as we age. If you are living with haemophilia, it's important to have a personalised treatment plan that protects you and helps you to feel safe so you can get on living your life to the full.

For example, when children living with haemophilia are growing up and playing with their friends, they might need to take slightly higher doses of their treatment at shorter intervals.

Or if you are an adult living with haemophilia and require surgery, your doctor will adjust your factor levels so that clotting works as it should during the surgery and through the healing process.

Likewise, if it's summer and you're off to hike up a mountain, you might be advised to take your treatment at shorter intervals on those more active days. But if you're headed to the beach to read a couple of books you might want to increase the intervals between treatments during those lazy days in the sun.

From these examples you can see how a treatment plan can be personalised to fit you and your individual needs - whatever they are - so that you can work towards your goals without haemophilia getting in the way.

Treatment possibilities

Of the haemophilia treatment options available, factor replacement therapy is the most common. It's a good idea to understand the different treatment options before talking to your doctor about which treatment is suited to your needs.

An introduction to factor replacement therapy


The main treatment for haemophilia is called factor replacement therapy and it works just like it sounds: it replaces the clotting factor (factor VIII (8) for haemophilia A, and factor IX (9) for haemophilia B) that your body doesn’t make or have enough of. This is done intravenously which means through a needle into a vein. Clotting factor products can either come from donated blood plasma or be recombinant, meaning they are made in a laboratory.

The World Federation of Heamophilia guidelines recommends that prophylaxis is used to prevent bleeding and joint destruction and it should be the goal of therapy to preserve normal musculoskeletal function. Prophylaxis decreases the number of bleeding episodes and may protect against joint disease and disruptions to quality of life. Traditionally, standard half-life (SHL) products have been used in replacement therapy. SHL is factor that lasts in the body for the same amount of time as the natural factor VIII, or factor IX. How often you need prophylaxis with SHL products depends on your personal needs and how you go about life, but people with haemophilia A usually need treatment three times a week and people with haemophilia B, twice a week3,4.

Not everyone with haemophilia chooses to, receive preventative treatment. Some people who could potentially be on prophylaxsis choose instead to get factor injections only when they bleed. Opting for on-demand treatments like this may be a personal choice but you should be aware that it could put you at higher risk of bleed-related joint damage.

 

What's 'half-life'?

 

You've probably heard a lot about "factor half-life" – but maybe you're not exactly sure what it is?

Basically, half-lite is the term for the amount of time the body takes to reduce the clotting factor to half in the bloodstream. Watch the film below! For a thorough explanation of the role of clotting factors and how there can a different half-life in each person.

Extended Half-Life (EHL) Factor


A newer type of factor replacement is called extended half-life (EHL) factor. This can last longer in the blood stream than standard factor, so many people on prophylaxis need treatment less often. For example, with haemophilia A, you may only need treatment twice a week instead of 3 times a week.27 For haemophilia B treatment may be weekly or even once a fortnight.28 Treatment for bleeds can be quicker too, with control after a single injection of EHL factor.5,6,7

There are currently three ways of producing EHL factor replacement: Fc fusion, PEGylation and albumin fusion. All of these techniques aim to prolong the half -life of clotting factors Vlll and IX by altering the structure of the protein molecules.   It might sound very scientific. but it basically means the body takes longer to remove protein from the blood so the clotting factor can work for longer and more efficiently after being injected7.

Bypassing and mimicking treatments

 

Some people with haemophilia A may stop responding to treatment. This is usually because they have developed antibodies, called inhibitors, against the clotting factors that are used to treat their haemophilia. Their body has simply started mistaking the replacement clotting factor as foreign invaders, and works to neutralise them. For these people, controlling a bleeding episode can be very difficult. But there is a way around this problem: instead of replacing the missing factor, special blood products called 'bypassing agents7 can be used to work around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. Bypassing agents are also licensed for non-inhibitor patients with haemophilia A.  

With mimicking treatment, an antibody mimics the function of factor VIII, rather than replacing the missing clotting factor VIII directly.

 

Other haemophilia therapies

 

  • Desmopressin (DDAVP). In cases of mild haemophilia, this synthetic hormone works by raising the levels of factor VIII in the blood. It can be injected slowly into a vien or provided as a nasal spray.
  • Clot-preserving medications (antifibrinolytics). These medications help prevent clots from breaking down.
  • Fibrin sealants. These medications can be applied directly to wound sites to promote clotting and healing. Fibrin sealants are especially useful in dental therapy.
  • Vaccinations. Factor replacement therapy that comes from human blood is routinely screened for viruses such as hepatitis and HIV. However, there is still a very small risk of contracting a disease from any blood product. If you have haemophilia it is important to be up to date on available vaccinations, including vaccines for hepatitis A and B.
  • Pain management Acute and chronic pain is unfortunately common for people living with haemophilia. The most effective way to help manage pain in haemophilia is to prevent bleeds, something which in turn can prevent repeated joint damage, a common source of chronic pain.
  • Physical therapy.This type of therapy can ease signs and symptoms if internal bleeding has damaged your joints.

 

Future Therapies


With gene therapy, researchers are trying to find ways to insert better functioning factor VIII or factor IX genes into the cells of people with haemophilia so their blood will clot more effectively. This method is not yet available and researchers are continuing to test it in clinical trials8.

 

What side effects are possible?


With any medicines, side effects are possible, although not everyone will experience these.
By reporting side effects, you can help provide more information on the safety of medicines. If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly via:

United Kingdom: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard
Ireland: HPRA Pharmacovigilance, website: www.hpra.ie; e-mail: medsafety@hpra.ie

You're in charge!

It’s totally normal- and usually encouraged - for you to self-treat if you have moderate or severe haemophilia. Although parents handle treatment and give intravenous injections for babies and small children, it is encouraged that children start to learn to do it themselves, which can create a sense of independence and confidence10. If you self-treat you’ll be free to enjoy your life without the worry of having to be close to your parent or carer in order to receive treatment.You can work with your haemophilia team to work out the best time to take your treatments to suit your lifestyle.

CARING FOR YOURSELF


With modern treatments your options are greater than ever before. However, despite great medical progress, as a person living with haemophilia. you will still need life-long treatment - whether it is prophylaxis or on demand injections.10 Having factor on hand is important because you never know when a bleed might occur and prompt treatment is important. So, whatever it is you are up to, be sure to keep your clotting factor with you - no matter if you are at home, being active or on vacation.

Yes, everybody’s treatment will be different, but being properly prepared and understanding how your factor levels are affected by your lifestyle is really important for everyone living with haemophilia. Learning to self-treat and being comfortable and confident in caring for yourself will help you feel liberated, so you can live life to the full and reduce the worry that today’s activities will limit tomorrow’s abilities.

FAQ - The fundamentals of haemophilia treatment

FAQ - New developments in haemophilia

Did you know that changing treatment is an option?

Make the most of your doctor's visit

REFERENCES

  1. Frequently asked questions.  World Federation of Hemophilia. https://elearning.wfh.org/elearning-centres/introduction-to-hemophilia.#hemophilia_faq. Last updated May 2012. Accessed November 2019
  2. Joint Damage. Hemophilla Federation of America. https://www.hemophiliafed.org/understanding-bleeding-disorders/complications/joint-damage/  Last updated N/A  Accessed June 2019.
  3. Haemophilia (Management: Approach). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/management-approach. Last updated April 2017. Accessed June 2019
  4. Haemophilia. BMJ Best Practice.  https://bestpractice.bmj.com/topics/en-gb/468/prevention. Last u dated April 2017.Accessed June2019
  5. Mahlangu J, Powell JS, Ragni MV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 2014, vol 123, issue 3, pp317-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894491/
  6. Santagostino E, Martinowitx U, Lissitchkov T et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825413 Accessed December 2019
  7. Alfonso Iorio et al (2016): Continuous prophylaxis with recombinant factor IX Fc Fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption. Journal of Medical Economics DOl:10.0180/13696998.2106.1265973
  8. Santagostin oE ,Martinwitx U  Lissitchltov T et al  Long-acting recombinant coagulation factor IX albumin fusion protein (rlX-FP )in hemophilia B:results lf a phase 3 trial. BLOOD April 2016.127(14). pp1761-9. In https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825413/ Accessed December 2019
  9. Clinical Commissioning Policy Emicizumab as prophylaxsis in people with congenital haemophilia A with factor VIII inhibitors (all ages) NHS England. https://www.england.nhs.uk/wp-content/uploads/2018/07/1717-emicizumab.pdf.  Published Jul 2018. Accessed 22nd August 2018
  10. Irish Haemophilia Society. Self-infusion. https://haemophilia.ie/living-with-haemophilia/parents/self-infusion .Accessed December 2019
  11. Guidelines for the Management of Hemophile (General care and management of Hemophilia: 1.6Prophylactic factor replacement therapy. World Federation of Hemophilia. https://www1.wfh.org/publications/files/pdf-1472.pdf   Last updated April 2013. Accessed December 2019

NP-9071
December 2019