Haemophilia Treatment types

Haemophilia A

Standard Half-Life (SHL) Factor Concentrates

The first type of treatment for haemophilia A to prevent or treat bleeds is FVIII ( factor 8) clotting factor concentrate replacement therapy, or replacing the deficient FVIII clotting factor. Until now, people with haemophilia have had access to two types of such treatments: plasma-derived or recombinant clotting factor therapies. Plasma-derived treatment is made from human plasma, while recombinant treatment is manufactured and genetically engineered from live non- human cell lines.

Half-life refers to the amount of time the body takes to reduce the clotting factor to half in the bloodstream. Standard half-life FVIII products have a half-life of between 8-12 hours.

Factor concentrates are infused (injected) into a vein at home by parents trained to treat their child, or by people themselves when they are confident enough to do it. It can also be carried out at the Haemophilia Treatment Centre.

Extended Half-Life (EHL) Factor concentrates

The average half-life (a measure of how long the protein stays in the body) of standard half-life (SHL) products are about 12 hours. Extended half-life products have been developed to improve these products’ allowing patients a treatment regimen with less frequent infusions for reasons such as poor venous access. The other option is that a higher trough ( lowest level the factor falls to before the next injection) level can be achieved and result in better protection. This option is often chosen for reasons such as bleeding even though prophylaxis is done, increased activity levels, severe joint damage or having short half-lives. The half-life of For factor VIII has been extended by an average of approximately 1.5 times.
The techniques used to increase half-life thereby allowing the FVIII to stay for longer in the system include the following:

  1. FC-Fusion
  2. Pegylation
  3. Changing the FVIII protein slightly to make it last longer

Non-Replacement Therapies

These are a new type of treatment. They provide a prophylactic effect, but without the use of factor concentrate, hence the name Non-(factor) Replacement Therapies (NRTs). Currently, there is only one product licenced. This is called Emicizumab- a bi-specific antibody, also referred to as a mimetic.

Normally, when you take FVIII, you are replacing the FVIII that is missing from the body. FVIII then connects two other proteins together. The bi-specific antibodies takes the portion of the FVIII protein that connects these two other proteins and puts them on to the ends of an antibody. So rather than the FVIII connecting the two proteins, it is the antibody that does this connection. So it is said to copy or “mimic” FVIII and hence is called a “mimetic” treatment.

These have several benefits. Firstly, they provide a consistent level of protection without peaks or troughs. There is no actual clotting factor infused provided, so they are not affected by FVIII inhibitors. Secondly, they are given subcutaneously (under the skin). They have long half-life’s so the number of injections per month is less. On the other hand, unlike factor concentrates they can not target the level of protection required for certain activities and they can not be used to treat a bleed. Conversations with a clinician are important to find which treatment is best to suit your lifestyle or your child’s lifestyle and activities and give you the best protection for your body short and long term.

Adjunct Therapies

These are therapies which are either used to supplement existing therapies or substitute for them in certain situations and sub groups.

Desmopressin (DDAVP)

Desmopressin (DDAVP) is a synthetic drug, identical to a hormone found normally in the body. It is not used in children under the age of 2 years or in adults over the age of 55 years.

How does it work?

DDAVP stimulates your body to release your own stores of clotting factors Factor VIII and VWF into the blood stream. This helps to boost vWF levels for up to 12-24 hours. If necessary, the dose of DDAVP can be repeated after 12 hours. As DDAVP is asking the body to release stored FVIII and vWF, if you have used it within the last 12 hours, the body doesn’t have the chance to rebuild its stores, so repeated doses may not be as effective.

DDAVP Trial

Some people do not respond to DDAVP. If this is the case, it is important to know this for your future treatment options. Treatment centres, hence suggest doing a DDAVP trial to find out if you are a “responder”, a “partial responder” or a “non- responder”.

The trial generally takes 3 hours for children and 6 hours for adults and some children. Blood samples are taken before and hourly after DDAVP infusion up to four hours. Occasionally a blood test will be needed on the following day. The response to DDAVP will be reported as one of the three following categories:

  • Responder: Your body responds well to DDAVP, resulting in a boost in VWF levels. DDAVP will be the treatment option for procedures and some bleeding episodes.
  • Partial responder: Your body responds only partially to DDAVP, resulting in a minor boost in VWF levels. This may be enough to cover minor procedures and minor bleeding episodes. An alternative treatment will be necessary for major procedures and major bleeding episodes.
  • Non-responder: Your body doesn’t respond to DDAVP. An alternative treatment will be necessary for all procedures and all bleeding episodes.

How is DDAVP given?

DDAVP is available as an intravenous injection which is often used in treatment centres and if needed at home can be available as a subcutaneous injection. For the intravenous injection it is slowly injected over thirty minutes to one hour.

Before DDAVP administration

Please inform your nurse / doctor of the following:

  • Any known reaction to this or any other medication
  • If you take diuretics, medication for high blood pressure or any other
  • medications, including over the counter medications and herbal remedies
  • Pregnancy or breastfeeding
  • Any significant medical problems including:
  • Heart disorder
  • Kidney disorder
  • Cystic fibrosis
  • Side Effects of DDAVP
  • Some people can experience flushing (reddening of skin or face) or increased heart rate during the infusion. If this occurs, please tell your team; often this will settle if DDAVP is given slower.

Other occasional side effects include:

  • Headache
  • Stomach pain and nausea
  • Allergic reactions
  • Decrease in blood pressure

In the elderly and in people with cardiovascular disease, DDAVP can cause more serious side effects and may not be recommended.

Fluid Intake

Adults should not drink more than 1 to 1.5 litres (approximately 8 to 10 cups) in the twenty-four hours following DDAVP. A child’s fluid intake is restricted to 75% of normal daily fluid requirement in the 24 hours following DDAVP. DDAVP can cause fluid to be retained by the body it is important to restrict fluid intake after the infusion of DDAVP. You will pass less urine in the 24 hours after the infusion. If you find you are passing little urine in 24 hours following the DDAVP treatment you should contact your Haemophilia centre. Treatment with DDAVP without reducing fluid intake may lead to fluid retention, dilution of salt in the blood, and in more severe cases, epileptic seizures. If these side effects occur, your doctor may advise an alternative treatment to DDAVP.

Tranexamic acid

Tranexamic acid (also known as Cyklokapron) is an anti-fibrinolytic agent. This means that it slows the breakdown of blood clots. It is used to prevent or treat bleeding from mucous membranes such as the inside of the mouth, nose, gut or womb. It may be given before dental work or for nosebleeds. It is often used in treating prolonged or heavy menstrual bleeding. It may be used alone or in combination with DDAVP and factor concentrates.

Hormone treatment

This is used in women with haemophilia A (severe, moderate, mild and carriers). Hormone treatment, such as oral contraceptives (birth control pills), can help women who have heavy menstrual bleeding.

The current treatment’s used for severe haemophilia in Ireland at present:
Haemophilia A:

  • Extended half Life Factor concentrates
  • Bi Specific antibody

Haemophilia B

Standard Half-Life (SHL)

The treatment for haemophilia B is aimed to prevent or treat bleeds using FIX ( Factor 9) replacement therapy. There are two types of treatments for people: plasma-derived or recombinant clotting factor therapies. Plasma-derived treatment is made from human plasma, while recombinant treatment is manufactured and genetically engineered from live cells.

Half-life refers to the amount of time the body takes to reduce the clotting factor to half in the bloodstream. Standard half-life FIX products have a half-life of approximately 8 hours.

Factor replacement concentrate are infused (injected) into a vein at home by parents trained to treat their child, or by people themselves when they are confident enough to do it.  It can also be done at the Haemophilia Treatment Centre if necessary.

Extended Half-Life (EHL)

The average half-life (a measure of how long the protein stays in the body) of standard half-life (SHL) products is about 18 hours. Extended half-life products have been developed to improve these products’ allowing patients a treatment regimen with less frequent infusions for reasons such as poor venous access.  The other option is that a higher trough level can be achieved and result in better protection. This option is often chosen for reasons such as bleeding even though prophylaxis is done, increased activity levels, severe joint damage or having short half-lives.  The half-life of  factor IX has been extended by an average of approximately 2.5 times.

The techniques used to increase half-life include the following:

  1. FC-Fusion
  2. Pegylation
  3. Albumin Fusion

Adjunct Therapies

These are therapies which are either used to supplement existing therapies or substitute for them in certain situations and sub groups.

Tranexamic acid

Tranexamic acid (also known as Cyklokapron) is an anti-fibrinolytic agent. This means that it slows the breakdown of blood clots. It is used to prevent or treat bleeding from mucous membranes such as the inside of the mouth, nose, gut or womb. It may be given before dental work or  for nosebleeds. It is often used in treating prolonged or heavy menstrual bleeding. It may be used alone or in combination with DDAVP and factor concentrates

Hormone treatment

This is used in women with haemophilia B (severe, moderate, mild and carriers).  Hormone treatment, such as oral contraceptives (birth control pills), can help women who have heavy menstrual bleeding.

The current treatment’s used for severe haemophilia in Ireland at present:

Haemophilia B: Extended half- life factor concentrates

Treatment approaches currently in clinical trials

Re-balancing agents

Coagulation factor concentrates- either FVIII or FIX replace the missing protein in the blood, thereby allowing the blood to clot. The body also has a number of naturally occurring anticoagulants which prevent the blood of a person without haemophilia from clotting excessively thereby causing clots to thrombosis.

A new approach to looking at haemophilia treatment is being looked at by a number of re-balancing agents currently in clinical trials. These treatments aim to remove, interfere with or decrease the naturally occurring anti coagulants thereby facilitating the blood to clot. There are a number of these therapies currently under development in clinical trials, some of which include people with haemophilia from Ireland.

These include:

  • Fitusiran
  • Anti- TFPI’s
  • Serpin
  • Gene Therapy