Identifying and overcoming barriers to prophylaxis in the management of haemophilia

Abstract

Haemophilia is often characterized by acute haemarthrosis and synovitis arising from spontaneous bleeding episodes, particularly in the muscles and joints of the elbows, knees and ankles. Current treatment for patients with severe haemophilia involves coagulation factor concentrate (CFC) replacement therapy given on demand at the time of bleeding or through long-term prophylaxis aimed at preventing future bleeds and joint disease. Although prophylaxis has many advantages over on-demand therapy (particularly if started before age 2 and prior to any signs of joint disease), its practice varies widely even among developed countries because of several barriers. Such barriers include CFC costs and availability; patient perceptions, lifestyles and bleeding patterns; difficulties and complications arising from the use of intravenous access devices (IVADs); the development of inhibitors; and the lack of randomized clinical trials. These barriers can be overcome by tailoring treatment regimens according to individual patient bleeding patterns and CFC pharmacokinetic profiles, using IVADs selectively and judiciously, helping patients maintain normal weight and physical exercise and providing the families of patients with continuous support from healthcare providers.

The History and Evolution of the Clinical Effectiveness of Haemophilia Type A Treatment: A Systematic Review

“…These results were backed by a prospective 10 year Italian trial (ESPRIT), which enrolled 40 patients younger than 7 years of age with negative clinical and radiological scores for joint damage; patients were randomized to be treated with rFVIII 25 IU Kg three times a week or on-demand (25 IU Kg) until complete bleed control, results indicated that prophylaxis is associated with significantly fewer breakthrough bleeds than on-demand treatment (0.24 vs. 1.30 bleeds per month, respectively; P \ 0.001) [18][19][20]. A retrospective cohort analysis involving 156 Norwegian and Swedish patients suggested that patients who received prophylaxis required fewer total invasive procedures than those who received on-demand treatment [21]. Less number of bleeding episodes, and lifethreatening haemorrhages under prophylaxis, should be associated with a much better joint status and a better quality of life.…”

“…It is intended to reduce the risk of other serious haemorrhage, such as intracranial bleeds [29]. In a study of 21 patients receiving secondary prophylaxis at three different ages (1-2, 3-6 and[6 years), Kreuz et al found that although the number of joint bleeds decreased significantly during prophylaxis in the two older groups, radiologic and orthopaedic scores still deteriorated for those who reported more than five joint bleeds before the initiation of prophylaxis, suggesting that once joint damage had started, further joint deterioration could not be prevented by the initiation of prophylactic therapy [21], even though secondary prophylaxis cannot reverse the changes of chronic arthropathy, it may be beneficial by reducing frequency of bleeding, hospital admissions and lost days from school or work, and by decreasing damage progression. Patients treated with secondary prophylaxis had a decreased number of joint bleeding episodes at the expense of higher clotting factor concentrate consumption [4].…”

“…Primary prophylaxis based on the Swedish protocol (also known as the high-dose Malmö protocol) involves the administration of 20-40 FVIII UI/Kg three times a week, and is currently considered the gold standard of care. This protocol is recommended by the WFH, WHO, the UK Haemophilia Centre Doctors Organization and the Medical and Scientific Advisory Council of the US National Haemophilia Foundation as the optimal treatment until a cure is available [21,24]. Nevertheless there are several protocols available and still being used.…”

“…A problem with this approach is that there are currently no standard criteria for determining unacceptable bleeds. Moreover, the long-term joint outcome of this approach and its protective effect against other serious bleeds is not known, because of the infrequent once-weekly dosing in many patients [21].…”

Haemophilia Treatment – Current and Future Challenges

“…However, the use of CVLs has been linked to a risk of infection of 0.2-1 per 1,000 days, and possible thrombosis. 7 Although the occurrence of thrombosis has historically been underestimated, it is now understood that it can occur in 15-53% of patients with CVLs, even with a diagnosis of haemophilia.…”