Haemophilia is a bleeding disorder where an individual does not have enough clotting factor and can bleed for a longer time. Since 1965, the introduction of factor replacement therapy (cryoprecipitate and later clotting factor concentrates) has enabled the substitution of the missing clotting factor in Haemophilia (the so-called ‘on demand’ treatment). For almost 40 years now, studies have provided definite evidence that preventing instead of treating bleeding by long-term regular prophylaxis started at an early age can avoid the clinical impact of Haemophilia and its effect on the quality of life of haemophilic children.

The concept of prophylactic therapy for Haemophilia first developed in Sweden and it necessitated regular scheduled infusions of clotting factors. Ever since then the prophylactic use of Factor VIII and IX concentrates has become an integral part of the management of haemophiliacs. Many studies have shown the benefits of prophylaxis versus on-demand factor replacement and it allows patients to have a better lifestyle by preventing the majority of bleeding episodes and preventing joint diseases secondary to bleeding joints.

What are the factors which affect prophylaxis?

The major factors which affect prophylaxis are:

– Physical activity

– The presence of target joints and synovial hypertrophy

– The degree of hemophilic painful joints

– The effect FVIII/FIX has on the underlying hemostatic system

– An individual’s pharmacokinetic response to FVIII/FIX

– Adherence to the regimen.

What are the different types of prophylaxis?

There are several types of prophylaxis:

– Non-stop/Continuous prophylaxis which are of primary, secondary, and tertiary sub types and 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

How is prophylaxis administered?

A prophylaxis schedule depends upon the type of factor product, weight, dose, frequency, and time (day or week) that the treatment is administered. It should be adjusted based on the observed pattern of bleeds, times of expected physical activity, and the status of the individual musculoskeletal system.

There are currently two protocols in use:

  1. Malmö protocol
  2. Utrecht protocol

What is the ideal time to initiate prophylaxis?

The optimal time to initiate prophylaxis is controversial. One school of thought advocates that prophylaxis be instituted during the second year of life when the patient is not bleeding or after the first joint bleed, whichever comes first, while the second school of thought believes that haemophiliacs should be started on prophylaxis only after they have developed a pattern of bleeding. Both the methods have associated pitfalls and advantages.

How are the outcomes of prophylaxis monitored?

Individuals receiving prophylaxis should have an assessment regularly. One important assessment tool is the WFH’s online tool.

What are the newer initiatives in prophylaxis?      

– Long acting concentrates: Clotting factor concentrate with extended half-lives, which can lead to less frequent and/or fewer injections to achieve the similar result

– Personalized prophylaxis: It is personalized, patient-tailored prophylaxis, whereby the dose and dosing frequency is individualized based on the pharmacokinetics (PK) data and has the potential to further optimize patient care and enable fewer infusions. There are devices which calculate dosage and frequency using that patient’s age and body weight for an individual patient 16 year of age or older and body weight of 45 kg or greater.

Barriers and Challenges

– Cost and access to treatment products: It is the biggest barrier. Though it is cost-effective in long term

– Venous access: An implanted venous access device (e.g., Port-A-Cath) can make injections much easier (which is tougher now) and may be required for administering prophylaxis in young children

– Adherence: It is critical to success and should be assessed regularly during clinic visits and strategies for improvements. Also, changes to the protocol should be explored wherever possible