Understanding your treatment

Understanding your treatment

Why do I need treatment?

 

Basically, 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 to clot (and stop the bleeding). For the clotting process, blood platelets along with special proteins, called coagulation 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 coagulation factor so that the blood can clot properly. 

Bleeds and what they do 

 

Without proper care and treatment, haemophilia can result in bleeding within joints. This bleeding can lead to things like chronic joint disease and pain; 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 depends on how low the level of clotting factors is 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, leading to chronic arthritis and disability. This is one of the main reasons it’s important to have a haemophilia treatment plan in place1.

So, to sum up: as all bleeds can be potentially dangerous, the ultimate 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 amazing human body has six main joint types

keep all of yours active to maintain their functionality.

understanding your treatment

Why every bleed matters

 

Joint disease is a common complication of haemophilia, so it’s important to try to prevent bleeding in order to protect your joints for the future. Joint disease or 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 circle which could potentially lead to long-term joint damage2.

Choose the treatment that's right for you

 

Just as haemophilia affects everyone differently, the treatment you choose can usually 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.

One size does not fit all


Everyone needs different protection for various stages and activities in life.

Illustration

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 fully personalised treatment plan that protects you and lets you feel safe so you can get on living your life to the fullest.

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 as an adult living with haemophilia require surgery after, say, a skiing accident, your doctor will adjust your factor levels so that your clotting works as it should. 

From these examples you can see how a treatment plan can be completely personalised to fit you and your individual needs – whatever they are – so that you can work towards your goal, reducing the risk of haemophilia getting in the way.

The treatment

With a handful of haemophilia treatment options, factor replacement therapy is the most common. The name might be a bit of a mouthful, but the treatment itself isn't so complicated. Even though you might have access to many different treatment options, it doesn't mean they're all suited to you and your needs. It's a good idea to understand what each treatment is about before talking to your doctor or deciding anything.

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 or 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. 

You may have replacement therapy on a regular basis to prevent bleeding. This is called preventive or prophylactic (pro-fih-lac-tik) therapy. Or, you may only need replacement therapy to stop bleeding when it occurs. This use of the factor treatment, on an as-needed basis, is called on-demand therapy.

The World Federation of Hemophilia guidelines recommend that prophylaxis (prof-ill-ax-iss) is the goal of therapy as it decreases the number of bleeding episodes and may protect against joint disease and disruptions to quality of life14. Traditionally, standard half-life (SHL) products have been used in factor 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.

Extended Half-Life (EHL) Factor

 

Extended half-life (EHL) treatments are newer types of clotting factor products for those being treated with factor replacement therapy. Compared to standard factor (SHL) products with a shorter half-life, this type of haemophilia treatment has been developed to last longer in the body while still providing effective protection from bleeds5
 
Clotting factors with EHL have been shown to provide positive, measurable changes in health, quality of life and bleed protection for people living with haemophilia6, 7, 8
  
Being treated with EHL gives you the possibility to personalise your treatment plan by matching the number of treatments per week with your current level of physical activity, all the while maintaining a high level of protection from bleeds. For this reason, EHL treatments have also been shown to make it easier to stick to your treatment plan6.
 
There are three main 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 VIII and IX by altering the structure of the protein molecules. It might all sound very scientific, but it basically means the body takes longer to remove the protein from the blood so the clotting factor can work for longer and more
efficiently after being injected10.

 

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-life 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 the clotting factors and how they can have a different half-life in each person.  

 

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 factors as foreign invaders, and works to neutralise them. For these people, controlling a bleeding episode can be very difficult. But there’s a way around this problem: instead of replacing the missing factor, special blood products called ‘bypassing agents’10 can be used to work around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot.  

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

Other treatments people with haemophilia might receive:

 

  • 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 vein 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’s 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. Understanding the cause of the pain is essential when choosing the right pain relief. The most effective way to manage pain in haemophilia is to prevent bleeds, something, which in turn can help 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 has not yet been developed to the point that it's an accepted haemophilia treatment but researchers are continuing to test gene therapy in clinical trials12.

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, haemophilia doctors and nurses recommend that children with haemophilia learn to do it themselves as soon as they’re old enough because of the sense of independence and self-esteem it can provide13. 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. Building confidence in injecting yourself gives you the option to be able to take control and time your treatments in a way best suited to your lifestyle. 

CARING FOR YOURSELF

 

With new preventative treatments like safer plasma products and manufactured clotting factors, your treatment and protection 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's preventative prophylaxis or on-demand injections14. Having factor on hand is important because you never know when a bleed might occur and prompt treatment is critical. So, whatever it is you're up to, be sure to keep your clotting factor with you — no matter if you’re at home, in the car, on vacation or just hanging out.  

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 reduce the worry that today’s activities will limit tomorrow’s abilities. 

Did you know that changing treatment is an option?

Make the most of your doctor's visit

As a person living with haemophilia, you have many possibilities for a life beyond haemophilia.
Read more by clicking below.

REFERENCES

1. Frequently asked questions. World Federation of Hemophilia. https://www.wfh.org/en/page.aspx?pid=637. Last updated May 2012. Accessed June 2019

2. Joint Damage. HemophiliaFederation 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 updated April 2017. Accessed June 2019

5. Shapiro et al, Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia. Expert Opin. Biol. Ther. (2013) 13(9):1287-1297

6. Practical aspects of extended half-life products for the treatment of haemophilia, TherAdv Hematol. 2018 Sep; 9(9): 295–308. Published online 2018 Sep 6. doi: 10.1177/2040620718796429

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, DOI:10.1080/13696998.2016.1265973.

8. A.Iorio et al, Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products, Haemophilia (2017), 23, 408–416.

9. Mahlangu J, Powell JS, RagniMV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophiliaA. Blood, 2014, vol 123, issue 3, pp317-25. http://www.bloodjournal.org/content/bloodjournal/early/2013/11/13/blood-2013-10-529974.full.pdf

10. SantagostinoE, MartinowitxU, LissitchkovT et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophiliaB: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In.

http://www.bloodjournal.org/content/bloodjournal/early/2016/01/11/blood-2015-09-669234.full.pdf. Accessed June 2019

11. Extended (or enhanced) half-life factor concentrates. The Haemophilia Society. https://haemophilia.org.uk/bleeding-disorders/treatment-types/longer-lasting-treatments/. Last updated N/A. Accessed June 2019 

12. Clinical Commissioning Policy: Emicizumabas prophylaxis 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 July 2018. Accessed 22nd August 2018

13. Hemophilia. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/hemophilia. Last updated N/A. Accessed June 2019

14. Guidelines for the Management of Hemophilia(General Care and Management of Hemophilia: 1.7 Home therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed June 2019

 

 

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Understanding your treatment

Why do I need treatment?

 

Basically, 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 to clot (and stop the bleeding). For the clotting process, blood platelets along with special proteins, called coagulation 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 coagulation factor so that the blood can clot properly. 

Bleeds and what they do 

 

Without proper care and treatment, haemophilia can result in bleeding within joints. This bleeding can lead to things like chronic joint disease and pain; 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 depends on how low the level of clotting factors is 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, leading to chronic arthritis and disability. This is one of the main reasons it’s important to have a haemophilia treatment plan in place1.

So, to sum up: as all bleeds can be potentially dangerous, the ultimate 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 amazing human body has six main joint types

keep all of yours active to maintain their functionality.

understanding your treatment

Why every bleed matters

 

Joint disease is a common complication of haemophilia, so it’s important to try to prevent bleeding in order to protect your joints for the future. Joint disease or 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 circle which could potentially lead to long-term joint damage2.

Choose the treatment that's right for you

 

Just as haemophilia affects everyone differently, the treatment you choose can usually 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.

One size does not fit all


Everyone needs different protection for various stages and activities in life.

Illustration

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 fully personalised treatment plan that protects you and lets you feel safe so you can get on living your life to the fullest.

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 as an adult living with haemophilia require surgery after, say, a skiing accident, your doctor will adjust your factor levels so that your clotting works as it should. 

From these examples you can see how a treatment plan can be completely personalised to fit you and your individual needs – whatever they are – so that you can work towards your goal, reducing the risk of haemophilia getting in the way.

The treatment

With a handful of haemophilia treatment options, factor replacement therapy is the most common. The name might be a bit of a mouthful, but the treatment itself isn't so complicated. Even though you might have access to many different treatment options, it doesn't mean they're all suited to you and your needs. It's a good idea to understand what each treatment is about before talking to your doctor or deciding anything.

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 or 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. 

You may have replacement therapy on a regular basis to prevent bleeding. This is called preventive or prophylactic (pro-fih-lac-tik) therapy. Or, you may only need replacement therapy to stop bleeding when it occurs. This use of the factor treatment, on an as-needed basis, is called on-demand therapy.

The World Federation of Hemophilia guidelines recommend that prophylaxis (prof-ill-ax-iss) is the goal of therapy as it decreases the number of bleeding episodes and may protect against joint disease and disruptions to quality of life14. Traditionally, standard half-life (SHL) products have been used in factor 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.

Extended Half-Life (EHL) Factor

 

Extended half-life (EHL) treatments are newer types of clotting factor products for those being treated with factor replacement therapy. Compared to standard factor (SHL) products with a shorter half-life, this type of haemophilia treatment has been developed to last longer in the body while still providing effective protection from bleeds5
 
Clotting factors with EHL have been shown to provide positive, measurable changes in health, quality of life and bleed protection for people living with haemophilia6, 7, 8
  
Being treated with EHL gives you the possibility to personalise your treatment plan by matching the number of treatments per week with your current level of physical activity, all the while maintaining a high level of protection from bleeds. For this reason, EHL treatments have also been shown to make it easier to stick to your treatment plan6.
 
There are three main 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 VIII and IX by altering the structure of the protein molecules. It might all sound very scientific, but it basically means the body takes longer to remove the protein from the blood so the clotting factor can work for longer and more
efficiently after being injected10.

 

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-life 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 the clotting factors and how they can have a different half-life in each person.  

 

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 factors as foreign invaders, and works to neutralise them. For these people, controlling a bleeding episode can be very difficult. But there’s a way around this problem: instead of replacing the missing factor, special blood products called ‘bypassing agents’10 can be used to work around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot.  

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

Other treatments people with haemophilia might receive:

 

  • 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 vein 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’s 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. Understanding the cause of the pain is essential when choosing the right pain relief. The most effective way to manage pain in haemophilia is to prevent bleeds, something, which in turn can help 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 has not yet been developed to the point that it's an accepted haemophilia treatment but researchers are continuing to test gene therapy in clinical trials12.

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, haemophilia doctors and nurses recommend that children with haemophilia learn to do it themselves as soon as they’re old enough because of the sense of independence and self-esteem it can provide13. 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. Building confidence in injecting yourself gives you the option to be able to take control and time your treatments in a way best suited to your lifestyle. 

CARING FOR YOURSELF

 

With new preventative treatments like safer plasma products and manufactured clotting factors, your treatment and protection 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's preventative prophylaxis or on-demand injections14. Having factor on hand is important because you never know when a bleed might occur and prompt treatment is critical. So, whatever it is you're up to, be sure to keep your clotting factor with you — no matter if you’re at home, in the car, on vacation or just hanging out.  

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 reduce the worry that today’s activities will limit tomorrow’s abilities. 

Did you know that changing treatment is an option?

Make the most of your doctor's visit

As a person living with haemophilia, you have many possibilities for a life beyond haemophilia.
Read more by clicking below.

REFERENCES

1. Frequently asked questions. World Federation of Hemophilia. https://www.wfh.org/en/page.aspx?pid=637. Last updated May 2012. Accessed June 2019

2. Joint Damage. HemophiliaFederation 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 updated April 2017. Accessed June 2019

5. Shapiro et al, Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia. Expert Opin. Biol. Ther. (2013) 13(9):1287-1297

6. Practical aspects of extended half-life products for the treatment of haemophilia, TherAdv Hematol. 2018 Sep; 9(9): 295–308. Published online 2018 Sep 6. doi: 10.1177/2040620718796429

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, DOI:10.1080/13696998.2016.1265973.

8. A.Iorio et al, Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products, Haemophilia (2017), 23, 408–416.

9. Mahlangu J, Powell JS, RagniMV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophiliaA. Blood, 2014, vol 123, issue 3, pp317-25. http://www.bloodjournal.org/content/bloodjournal/early/2013/11/13/blood-2013-10-529974.full.pdf

10. SantagostinoE, MartinowitxU, LissitchkovT et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophiliaB: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In.

http://www.bloodjournal.org/content/bloodjournal/early/2016/01/11/blood-2015-09-669234.full.pdf. Accessed June 2019

11. Extended (or enhanced) half-life factor concentrates. The Haemophilia Society. https://haemophilia.org.uk/bleeding-disorders/treatment-types/longer-lasting-treatments/. Last updated N/A. Accessed June 2019 

12. Clinical Commissioning Policy: Emicizumabas prophylaxis 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 July 2018. Accessed 22nd August 2018

13. Hemophilia. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/hemophilia. Last updated N/A. Accessed June 2019

14. Guidelines for the Management of Hemophilia(General Care and Management of Hemophilia: 1.7 Home therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed June 2019

 

 

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