Treatment

Treatment options for VWD


Licensed Clotting Factor Concentrates

• Human plasma derived dual factor Concentrate
• Human plasma derived single factor
• Recombinant single factor Concentrate

By-Passing Agents (for Inhibitors only)

• Human plasma Activated Prothrombin Complex (aPCC)
• Recombinant rFVIIa)

Adjunct Therapies

• DDAVP/Desmopressin (Type I /II, vWD)
• Fibrin Glue
• Tranexamic Acid

For Women

• Hormone treatment (Women/Girls)
• Intrauterine Devices
Clinical Trials Non-Factor replacements (Prophylaxis only)
• Bi-Specific Antibodies
• Rebalancing Therapies
• Aptamers

Desmopressin (DDAVP)

Desmopressin (DDAVP) is a synthetic drug, identical to a hormone found normally 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 fi nd 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 (Cyklokapron)

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, for nosebleeds. It is often used in treating prolonged or heavy menstrual bleeding. It may be used alone or in combination with DDAVP and von Willebrand factor

Factor replacement therapy

Factor concentrate is given into a vein to replace the missing vWF to allow clotting to take place. There are two types of factor replacement available for vWD. The first is made from pooled human plasma, (which is screened for blood-borne viruses such as HIV and hepatitis B and also treated to destroy viruses). This also contains FVIII. The newest option is recombinant vWF (rvWF) which is engineered in a laboratory. The type of product used can be dependent on the type of bleeding that you are being treated for, as well as the type of vWD you have.

There is one difference in vWD when being treated. Some products also contain varying amounts of FVIII. This can be both helpful or unhelpful depending on the type of bleeding and when using for prophylaxis. This makes the choice of product a bit more complicated than other bleeding disorders.

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.

Hormonal Contraceptive therapy

Hormonal contraceptives reduce menstrual bleeding by thinning the endometrium and possibly increasing factor VIII and von Willebrand factor levels. They have an added advantage of controlling ovulation bleeding and midcycle pain. Hormonal contraceptives currently available include combined oral contraceptive pill (COC), transdermal contraceptive patches, oral progestogens, Progestin-only pills or implantable, Gonadotropin-releasing hormone (GnRH) analogues.

Most women who use hormonal contraceptives have very few or no side effects. Serious side effects of hormonal contraceptives include high blood pressure, liver abnormalities and clots. Women with inherited bleeding disorders, however, may have a lower risk of clotting. Side effects that some women experience are nausea, headaches, dizziness, breast tenderness and mood changes. Some of these side effects improve over the first 3 months. If the side effects continue the doctor may prescribe a different brand of hormonal contraceptive.


Intrauterine device (IUD, e.g. Mirena®)

An IUD has been shown to be useful for reducing menstrual blood loss in women with bleeding disorders. The licensed duration of use in Ireland is five years i.e. once inserted it may stay in place for 5 years. Side effects may be irregular bleeding or spotting, especially within the first 6 months. There is a potential risk of bleeding at the time of insertion and preventative treatment with a haemostatic agent may be required.