Summary
- Rebalancing therapies are a type of non-factor therapy used for people with haemophilia.
- Non-factor therapies don’t replace clotting factor – they support the body to clot in other ways.
- Rebalancing therapies work by balancing clotting factors with anti-clotting factors in the blood.
- These therapies are injected under the skin (subcutaneously).
- They are only used as prophylaxis (preventive treatment). If you have a bleed, you need clotting factor replacement therapy to treat it.
What are rebalancing therapies?
Rebalancing therapies are a type of non-factor therapy for people with haemophilia.
Haemophilia occurs when a person doesn’t have enough of a specific clotting factor in their blood to control bleeding properly. A clotting factor is a protein in blood that controls bleeding.
- People with haemophilia A don’t have enough clotting factor VIII (8).
- People with haemophilia B don’t have enough clotting factor IX (9).
Non-factor therapies don’t replace factor VIII or factor IX like clotting factor replacement therapy. Instead, they support the body to clot in other ways. Rebalancing therapies can be used to treat both haemophilia A and haemophilia B, whether or not a person has inhibitors.
How rebalancing therapies work
When a person has an injury that causes bleeding, more than 20 proteins are involved in the chain reaction to make a clot that stops the bleeding, including multiple clotting factors. These factors trigger a process that produces thrombin, a protein that helps with clotting.
People with haemophilia don’t have enough of a specific clotting factor – factor VIII in haemophilia A or factor IX in haemophilia B. This means their bodies don’t make enough thrombin.
This creates an imbalance: there are not enough clotting factors compared with the natural anti-clotting (anticoagulation) factors in the blood.
Rebalancing therapies lower the levels of these anti-clotting factors. This helps restore the balance and allows the blood to clot more normally.
Source: adapted from eLearning Centre, Non-factor replacement therapy © World Federation of Hemophilia 2024.
Types of rebalancing therapies include:
Tissue factor pathway inhibitors (TFPIs): these treatments are monoclonal antibody therapies, proteins made in a laboratory that imitate natural antibodies in the immune system. They target TFPI, a natural anti-clotting protein. By blocking TFPI, they help increase how much thrombin the body makes, which then increases clotting.
Examples are:
- concizumab (for people with haemophilia A or B, with or without inhibitors)
- marstacimab (for people with haemophilia A or B without inhibitors)
Small interfering RNAs (siRNAs): these treatments target another clotting protein called antithrombin. They ‘silence’ antithrombin, reducing how much of it the body produces, which then allows thrombin production to increase and help with clotting.
An example is:
- fitusiran (for people with haemophilia A or B, with or without inhibitors)
Unlike clotting factor replacement therapy, these therapies do not change your clotting factor levels. Instead they maintain a constant level of protection, similar to having mild haemophilia.
In clinical studies people on rebalancing therapy have had between about 0 and 3 bleeding episodes (‘bleeds’) per year.
Who rebalancing therapies are for
Currently in Australia these treatments have only been available in clinical trials. They are for people with haemophilia A or B aged 12 years or older. Some products are more appropriate for people without inhibitors, while others are for both people who have inhibitors and those who do not.
Treatment with rebalancing therapies is only for prophylaxis – regular treatment to prevent bleeds or to reduce bleeding from injuries.
How the treatment is given
Treatment for haemophilia is usually prescribed by a haematologist (a doctor who specialises in blood diseases) or a haemophilia nurse practitioner at a Haemophilia Treatment Centre (HTC).
Haemophilia treatment plans are personalised. These plans are developed specifically for you and your circumstances and can be updated whenever needed. Your treatment plan may include a plan for regular prophylaxis treatment and a plan for injuries or surgery.
Australian governments fund a range of clotting factor and other blood products used to treat haemophilia through the National Blood Authority. This means the approved products are provided at no cost to patients who need them.
Treatment safety
All medicines can have side effects.
The most common initial side effects are skin reactions (itching, rash, redness) at the spot where the treatment is injected and headaches. Other common side effects depend on the product and may include joint pain, infections, impact on liver function and gall bladder disease.
Some people using rebalancing therapies can develop serious blood clots in the veins and arteries called thromboembolic events. Your treating team may need to monitor you with blood tests at various points and consider other health conditions that may impact on this treatment.
So far, the safety and how well these therapies work is similar in adults and adolescents over 12 years. They haven’t been fully tested yet in children under 12.
New and emerging treatments
Researchers are always looking for new ways to treat haemophilia. Non-factor therapies are still a relatively new treatment option for haemophilia and there is ongoing research and development to improve these types of therapies.
Keep in touch with your HTC to find out what’s new, discuss your treatment options and determine which one would be best for you. You can also stay up to date with new and emerging treatments through Haemophilia Foundation news, websites and education sessions, including the Australian Bleeding Disorders Conference.
Living well with haemophilia treatment
Managing your haemophilia treatment well can help you enjoy a full life. Big treatment changes can also affect mental health, even when the results are positive. Your HTC is there to give advice and support. They can refer you to other services if you need them. Although everyone’s experience can be different, connecting with other people with haemophilia to share common experiences and tips can be valuable. Your HTC and your local haemophilia foundation can help with this.
Travel
Many people with haemophilia travel both within Australia and overseas. This can involve a little extra planning and discussion with your HTC. Check the locations and available times of HTCs in the places where you’re travelling before you set off, in case you run into trouble.
You may need to take treatment product with you. This may involve carrying it with you in a cooler bag and storing it in a fridge on your trip. If you’ll be away for a long time or going overseas, start planning with your HTC early.
Your HTC can also help with documents for customs and security. You may also wish to carry your ABDR (Australian Bleeding Disorders Registry) patient card with your diagnosis and treatment plan in your wallet or on your phone, set up your medical emergency info on your phone or to wear a medical alert bracelet or necklace.
Be informed and aware
Understanding your haemophilia and knowing how to manage it makes a big difference.
- Be aware of how your body responds to treatment and plan around it.
- Build a good relationship with your haemophilia team and don’t be afraid to ask questions.
- Keep up with the latest treatments and services.
More information
For more information, speak to your HTC.
Visit the Haemophilia Foundation Australia website for:
- the Gene and Emerging Therapies Hub
- contact details for Haemophilia Treatment Centres (HTCs), which are located in every state and territory.
References
The figure in this resource was originally published by the World Federation of Hemophilia (WFH) and has been adapted with permission. The WFH is not responsible for any inaccuracies in content different from the content of the original English edition.
World Federation of Hemophilia. Shared Decision Making Tool: Hemostatic rebalancing therapy fact sheet. WFH: Montreal, 2025. https://elearning.wfh.org/resource/hemostatic-rebalancing-therapy-fact-sheet/
Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020: 26(Suppl 6): 1-158. Accessed 1 August 2022. Available from https://doi.org/10.1111/hae.14046.
Peyvandi F, Seidizadeh O, Mohsenian S, Garagiola I. Exploring nonreplacement therapies’ impact on hemophilia and other rare bleeding disorders. Research and Practice in Thrombosis and Haemostasis 2024;8(4):102434. https://doi.org/10.1016/j.rpth.2024.102434.
Reviewers:
HFA Gene and Emerging Therapies consumer review Group (individuals not named for privacy reasons).
Australian Haemophilia Centre Directors’ Organisation: Dr Sally Campbell, Dr Stephanie P’ng. ABDR Data Managers: Marina Goruppi, Venessa Mavrinac-Tiddy.
ANZ Haemophilia Psychosocial Group: Tanya Grueneweld, Jane Portnoy, Emma Wells.
Australian Haemophilia Nurses’ Group: Megan Walsh.
The video resources on this page are published by World Federation of Hemophilia (WFH) and are linked here with permission.
© 2023 World Federation of Hemophilia https://sdm.wfh.org/
This fact sheet has been funded by unrestricted education grants from CSL Behring and Sanofi. HFA does not promote any particular pharmaceutical product.