Primary prevention

No strategies have been identified to prevent this condition. However, bleeding episodes and some complications can be prevented.

Secondary prevention

Prophylaxis should be considered standard of care therapy for individuals with severe haemophilia A or B (factor VIII or factor IX <1%), including those with inhibitors.[68] It is defined as the regular administration of a haemostatic agent/agents with the goal of preventing bleeding in people with haemophilia while allowing them to lead active lives and achieve quality of life comparable to non-haemophilia individuals.[38]

There are different types of prophylaxis:[1][83]

  • Primary prophylaxis refers to therapy initiated in young patients with haemophilia, prior to the second evident large joint bleed and before the age of 3 (preventive therapy)

  • Secondary prophylaxis refers to therapy initiated after 2 or more bleeds into large joints, and before the onset of established joint disease

  • Tertiary prophylaxis refers to therapy started after the onset of joint disease.

Prospective open-label and observational studies suggest that prophylaxis is superior to episodic treatment in delaying or preventing joint arthropathy, even in patients with severe haemophilia.[85][87][157]

For haemophilia A, the typical infusion schedule is 2 to 3 times weekly with standard recombinant or plasma-derived factor VIII, or once every 5 to 7 days for extended half-life (long-acting) factor VIII.[158] Standard recombinant or plasma-derived factor IX is usually administered twice weekly for haemophilia B; however, extended half-life (long-acting) factor IX molecules are generally administered once every 7 to 14 days to maintain trough levels of 3% to 5% or higher.​[38]

Prophylaxis is recommended following the initial treatment of intracranial bleeding.[83] In this scenario, different treatment regimens have been suggested, ranging from every-other-day infusions to weekly infusions.

Emicizumab prophylaxis in patients with haemophilia A

Emicizumab, a humanised monoclonal antibody that mimics the function of factor VIII without being affected by factor VIII inhibitors, is approved by the European Medicines Agency and the US Food and Drug Administration for prophylaxis in haemophilia A patients with and without inhibitors.[69][92][93]

Emicizumab is administered subcutaneously and can be given in weekly, biweekly, or at 4-week intervals. Emicizumab has a long half-life and its plasma level remains constant (without peaks and troughs as in clotting factor prophylaxis) once a steady-state is reached after loading doses over the initial 4 weeks.

In patients with haemophilia A with or without inhibitors, emicizumab is associated with substantial and meaningful improvements in health-related outcomes.[94] Emicizumab cannot be used to treat acute bleeds or to cover surgical procedures, and cannot be used for haemophilia B prophylaxis.

Emicizumab will interfere with the activated partial thromboplastin time assay, one-stage based assay for clotting factor activity, and factor VIII inhibitor titre. When using emicizumab, a chromogenic assay using bovine reagents should be used for quantitation of endogenous or infused factor VIII levels, and a chromogenic Bethesda assay using bovine reagents should be used for quantitation of factor VIII inhibitor.[61][95] Factor VIII inhibitor bypassing fraction (an activated prothrombin complex concentrate [aPCC]) should be avoided when patients are taking emicizumab to prevent the occurrence of thrombotic microangiopathy and thrombosis.[61][95]

Bleeding prevention for surgery and trauma

Measures include:

  • Desmopressin for people (with a demonstrated positive response to desmopressin) with mild haemophilia A (factor levels >5%) having minor surgery or minor dental procedures.[69]​​

  • Factor VIII or factor IX infusion, recommended for people with moderate and severe haemophilia A or B, respectively, undergoing minor surgery or minor dental procedures, or for patients having major surgery. Repeat doses may or may not be required depending on the extent of the procedure and risk of bleeding.

  • Patients with inhibitors undergoing major surgery should receive bypassing agents first-line.

  • For procedures associated with risk of mucosal bleeding, such as oral, dental, nasal, or gastrointestinal surgery, an antifibrinolytic agent is recommended orally every 6 hours for 7 to 10 days, beginning the night before the procedure. Aminocaproic acid can be given intravenously following oral or ear, nose and throat surgery.[69] Antifibrinolytics should be avoided if the patient has haematuria.

Preventive measures also include patient and family education, including the need to avoid contact sport and trauma (if possible). For immunisations, subcutaneous administration may be considered in preference to intramuscular injection. However, it is not clear if the benefit of reducing the risk of intramuscular haematoma outweighs the potential risk of reduced efficacy for some vaccines. Pneumococcal polysaccharide, inactivated polio, hepatitis A and hepatitis B have been shown to maintain efficacy when administered subcutaneously.[50][153]​​​​​ Hepatitis A and B immunisations are recommended alongside all routine immunisations.[154] A fine-gauge needle (23 gauge or smaller) may be used and firm pressure applied to the site for at least 2 minutes before injection. Treatment may also be considered before immunisation to reduce the risk of haematoma, depending on the patient's factor level. For patients receiving prophylaxis, vaccination may be coordinated with prophylaxis administration to reduce the risk of haematoma.[50]

Patients should be encouraged to take regular exercise appropriate to joint status, especially swimming, to improve their quality of life.[155][156]​​ Annual assessment with a physical therapist is recommended, with ongoing education and support, including advice on physical activity and healthy living.[77]

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