In this section we will briefly review the different types of treatment options available to people with congenital bleeding disorders:
- About treating bleeding disorders
- Factor concentrates
- Non replacement therapies
- Prothrombin complex concentrate (PCC)
- Fresh frozen plasma (FFP)
- Antifibrinolytic drugs
- Fibrin glue
- Platelet transfusions
- Hormonal contraceptives
- Intra-uterine devices (IUDs)
- Hepatitis C treatment options
Unlike other rare conditions, haemophilia benefits from a range of commercial treatment available in Europe. However, this is not the case for other rare bleeding disorders, which still lack adequate treatment options. Currently in Europe, the cost of such treatments is one of the main barriers for people with bleeding disorders to access their treatment. In fact treatments can be extremely expensive, amounting to several hundreds of thousands of euros per year. This is why the patients’ community works hand in hand with regulators and manufacturers to ensure that these products are put on the market at the most accessible price, hence ensuring that the maximum number of people with bleeding disorders can access adequate treatment.
This section provides a short overview of the treatment options currently used to treat bleeding disorders. For further information regarding the marketing authorisation of a specific product, please consult the website of the European Medicines Agency (EMA) and your national competent authority. For more information regarding the reimbursement of a product, please consult your national health insurance company.
You can find information about treatment guidelines, treatment products available in Europe and haemophilia treatment centres on the Haemophilia Central website. You can also find information about available products in Europe on the European Haemophilia Safety Surveillance website.
Factor concentrates are medicinal products containing the missing factor in a person with bleeding disorders. The factor is infused intravenously in a patient on a regular basis. This is called replacement therapy. Unfortunately for people with rare bleeding disorders, there are few factor-specific treatments available and many patients rely on inadequate treatments such as Fresh Frozen Plasma and Cryoprecipitate.
Factor concentrates can be made either from human plasma or they can be genetically engineered. When made from human plasma, a range of safety measures is taken to make sure that there is no viral contamination of the product and that people receiving the treatment are not infected with viruses such as HIV and and hepatitis C (HCV). For this purpose, there are strict criteria that are implemented in the choice of the plasma donors and manufacturers have developed a series of viral removal or viral inactivation steps that are used during the manufacturing process. Nonetheless, patients should be aware that a theoretical risk of contamination still remains for plasma-derived treatments. This risk could be linked to either emerging pathogens or variant Creutzfeldt-Jakob Disease (vCJD) for which it is still unclear whether it can be transmitted through plasma-derived products.
Factor concentrates are administered intravenously. This can be particularly cumbersome and distressing, especially in babies and children, as the infusion is done every couple of days. This can also create longer-term problems such as damages to veins. Once a new patient is diagnosed, the treatment should be performed in a medical setting to monitor potential allergic and adverse reactions and the development of inhibitors. However, once the first stage is passed many countries allow people with bleeding disorders to administer treatment at home without medical supervision. This considerably increases patients’ quality of life as there is no need to travel to a medical setting and therefore the infusions interfere less with patients’ professional and private lives.
In 2018 a new treatment product was licensed in Europe that completely changes the landscape for many people with bleeding disorders, especially those with haemophilia A and inhibitors. Prophylaxis with emicizumab (Hemlibra ®, Roche) is now regarded as the optimal therapy in patients with persistent inhibitors. Clinical studies have demonstrated superior outcomes with this agent compared to previous treatment regimes with bypassing agents alone. The advantages of emicizumab are that it is given by subcutaneous injections at intervals of 1-4 weeks and enables a steady plasma concentration to be maintained (after initial loading doses). This novel therapy requires close supervision in haemophilia comprehensive care centres.
Prothrombin complex concentrate (PCC)
This concentrate is made from human plasma and contains a mixture of clotting factors, including factors II, VII, IX and X (however, some products do not contain all four factors). PCC is suitable for individual deficiencies of factor II and X as well as inherited combined deficiency of the vitamin K-dependent clotting factors (VKCFD). It is treated to eliminate viruses like HIV and hepatitis B and C. Some PCCs have been reported to cause potentially dangerous blood clots (thrombosis). PCC is administered intravenously.
Fresh frozen plasma (FFP)
Plasma is the portion of blood that contains all the clotting factors, as well as other blood proteins. FFP is used to treat rare bleeding disorders when concentrates of the specific factor that is missing are not available. FFP is the usual treatment for factor V deficiency. However, it usually does not undergo viral inactivation, so the risk of transmission of infectious diseases is higher. Viral-inactivated FFP is available in some countries and is preferable. Circulatory overload is a potential problem with this treatment: since the concentration of each coagulation factor in FFP is low, a large volume of it must be given over several hours in order to achieve an adequate rise in factor level. This large amount of FFP needed can overload the circulatory system and stress the heart. Other complications of treatment with FFP can occur, particularly allergic reactions or lung problems (transfusion-related lung injury [TRALI]). These problems are much less common if viral-inactivated pooled FFP is used. FFP is administered intravenously.
Made from human plasma, cryoprecipitate contains factor VIII, fibrinogen (factor I) and a few other proteins important for blood clotting. While it is possible to virally inactivate cryoprecipitate, it is not common practice and therefore cryoprecipitate should only be used when factor concentrate is not available. It contains higher concentrations than FFP of some (but not all) coagulation factors, so less volume is needed. It is only suitable for a few deficiencies. Cryoprecipitate is administered intravenously.
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Desmopressin is a synthetic hormone that raises the levels of factor VIII in patients with combined factor V and factor VIII deficiency. Since it is man-made, there is no risk of transmission of infectious diseases. Desmopressin has no effect on the levels of any of the other coagulation factors. It can be administered intranasally or intravenously.
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The antifibrinolytic drugs tranexamic acid and aminocaproic acid are used to hold a clot in place in certain parts of the body, such as the mouth, bladder and uterus. These drugs are very useful in certain situations, such as during dental work, but are not effective for major internal bleeding or surgery. Antifibrinolytic drugs are particularly useful for patients with factor XI deficiency. They are also used to help control excessive menstrual bleeding. Antifibrinolytic drugs can be administered orally or by injection.
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Fibrin glue can be used to treat external wounds and during dental work, such as a tooth extraction. It is not used for major bleeding or surgery. It is applied to the bleeding site.
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Platelets are small blood cells that are involved in the formation of blood clots and the repair of damaged blood vessels. Certain clotting factors, including factor V, are stored in small sacks inside them. Platelet transfusions are sometimes used to treat factor V deficiency.
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Hormonal contraceptives (birth control pills) help control menstrual bleeding.
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Intra-uterine devices (IUDs) help control menstrual bleeding.
These treatments may have side effects, so people with rare clotting factor deficiencies should talk to their physician about the possible side effects of this treatment.
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Many people with bleeding disorders and in particular people with haemophilia were contaminated with hepatitis C (HCV) and HIV during the 1980s. Thanks to medical advances, there are now several types of treatment options available in Europe that effectively cure the hepatitis C virus.
You can read more about current treatments for HCV in the EHC Newsletter from August 2014.
Adapted from the World Federation of Hemophilia website