Prophylaxis is the regular administration (intravenously, subcutaneously, or otherwise) of a hemostatic agent with the goal of preventing bleeding (especially life threatening or recurring joint bleeding) in people with hemophilia. The goal of prophylaxis is for people with hemophilia to lead active lives, and to achieve quality of life that is comparable to non-hemophilic individuals.
Prophylaxis should be the standard of care everywhere in the world. The clinical recommendation of prophylaxis comes from the scientific observation of patient data that people with moderate or mild hemophilia (who have clotting factor levels at 1% or above) experience far less spontaneous bleeding. They have less joint damage than people who have severe hemophilia (who have less than 1% clotting factor) and an improved quality of life.
Unlike on-demand therapy, which is a reactive response to stopping a bleed that is in progress, prophylaxis is given to prevent bleeding before it starts. On-demand therapy may reduce the pain and debilitating impact of individual bleeds, but it cannot significantly alter the bleeding profile.
Therefore, on-demand therapy does not change the natural progression of hemophilic arthropathy, which leads to musculoskeletal damage and other complications caused by bleeding. The use of prophylaxis is always recommended and preferred over on-demand therapy, as the ideal is for people with hemophilia to not experience any bleeds (i.e., achieve “zero” bleeds), as each bleed can cause damage, especially in the joints.
Studies on prophylaxis show that:
Doctors recommend that people with hemophilia A or B who have a severe bleeding profile should be on prophylaxis sufficient to prevent bleeds at all times. This should be individualized, taking into consideration:
There are several types of prophylaxis, defined according to when prophylaxis starts.
Continuous prophylaxis is given regularly over a period of several months and often years:
Intermittent or periodic prophylaxis is given for shorter periods of time, usually a few weeks or months, such as after surgery or for physiotherapy/rehabilitation.
Prophylaxis treatment options now include standard half-life (SHL) and extended half-life (EHL) replacement therapy and non-factor replacement therapy. As of publishing this booklet, only one non-factor replacement therapy is available for people with hemophilia A, while SHL and EHL CFCs are available for people with hemophilia A or B.
Regular replacement therapy
Prophylaxis with SHL and EHL CFCs is referred to as regular replacement therapy. It involves the regular infusion of the missing clotting factors with the aim of raising the levels such that bleeding stops (FVIII for people with hemophilia A, and FIX for people with hemophilia B).
Prophylaxis with regular infusion of CFC attempts to raise clotting factor levels and to always keep them at 1% or higher. Different dosing regimens (high-, intermediate-, or low-dose), using either SHL or EHL CFCs, are used to achieve this. People with hemophilia should consult with their local physician or Hemophilia Treatment Centre (HTC) as part of their treatment plan.
A prophylaxis treatment plan and schedule using CFCs should include the following:
Extended half-life replacement therapy
EHL CFCs have been designed to maintain factor levels for a longer period in the blood. Overall, EHL CFCs allow people with hemophilia to:
Tailored prophylaxis for SHL and EHL replacement therapy
Tailored prophylaxis regimens are individualized to the needs of each person: people with hemophilia get a prophylaxis regimen based to their own needs. Prophylactic regimens should also be flexible enough to change with time as the individual’s circumstances change; if people with hemophilia continue to experience bleeds, their prophylaxis regimen should be increased (in dose, frequency, replacement therapy or any combination) to prevent bleeding.
An effective, tailored, prophylaxis protocol considers the following:
Non-factor replacement therapy
Non-factor replacement therapies use other mechanisms to allow the body to stop bleeding due to deficient clotting factors in people with hemophilia. At the time of publication (2021), only one product (emicizumab) is available and licensed as non-factor replacement therapy for Factor VIII, including those with hemophilia A who have an inhibitor. Other therapies are currently in clinical trials and may come to market over the next few years.
Emicizumab does not replace the missing Factor VIII in people with hemophilia A, instead it mimics FVIII’s function so that the clotting process can proceed. Emicizumab can only be used as prophylaxis in people with hemophilia A. It is not used to treat acute bleeding episodes. Thus, CFCs will still be required for treatment of acute bleeding.
Other benefits of emicizumab include:
CAUTION: While on emicizumab, people with hemophilia who have inhibitors should not be given activated prothrombin complex concentrate (aPCC) to treat breakthrough-bleeding episodes, as this may result in a clotting thrombotic event. (Please consult the HTC and risk management guidance for more information.)
The best approach is to start prophylaxis as early as possible, to preserve joint health and prevent joint disease. Where access to CFCs is limited, lower doses are an effective option. Subcutaneous treatment can address the challenges of accessing veins. This may allow prophylaxis to be started at a much earlier age, and may reduce the risk of bleeding that occurs in very young children (<12 months), before traditional prophylaxis usually begins. As of publication (2021), studies are ongoing to determine the safety of emicizumab in this age group.
A person with hemophilia who continues to benefit from effective prophylaxis (which means having less bleeding episodes, better joint health, and improved quality of life), should continue with prophylaxis indefinitely. This is a recommendation commonly shared by the World Health Organization, the World Federation of Hemophilia, and many other international and national organizations involved with hemophilia care.
|If you (or your child) are not yet on prophylaxis, talk to your doctor or health care team about starting.||Think it is too late to begin prophylaxis – although prophylaxis cannot reverse joint damage, it may slow the progression, improve quality of life, and decrease frequency of bleeding.|
|Start prophylaxis as early as possible.||Skip or postpone your treatment schedule.|
|Advocate for individualized, or tailored, prophylaxis.||Expect prophylaxis to reverse joint damage.|
|Follow the dosage schedule that is given to you by your doctor or health care team.||Wait for your next appointment if you have an adverse reaction or bleeding – see your doctor immediately.|
|If you experience an adverse event while on prophylaxis, see your doctor immediately; this includes bleeds.||Ignore break-through bleeds, especially recurring in the same joint, as they may lead to a target joint.|
|Talk to your health care team about the possibility of home therapy or shared care with local health care providers.|
|Have regular checkups with your HTC to review your prophylaxis treatment plan.|
|Keep track of your treatment in a logbook including any adverse events (see next page for more details).|
|If prophylaxis isn’t working for you, see your doctor.|
It is important to record the following information when you receive prophylaxis, so that your doctor can follow-up with you and make sure you are on the right treatment for you as an individual.
There are many ways to keep track of bleeding episodes and treatments:
Please check with your HTC if they have a preferred method.