Haemophilia A and B
releasable pool and by releasing VWF from endothelial cells. As noted above, VWF serves as a carrier protein for FVIII in plasma and protects it from proteolytic degradation. The effect of DDAVP decreases after two to three consecutive administrations, due to depletion of storage pools. As there are large inter- individual differences in the response to DDAVP, the effect of a test dose of DDAVP should be evaluated in each individual patient. DDAVP cannot be used in the treatment of haemophilia B. For mucocutaneous bleeding in haemophilia A and B, (supplementary) treatment with tranexaminic acid is effective (25–50 mg/kg/day; maximum dose of 4 gram in three to four oral or intravenous doses).
Medication that impairs haemostasis, such as platelet inhibitors and anticoagulant drugs, should be avoided whenever possible, as these will aggravate bleeding symptoms.
Use of prophylaxis
Repetitive joint bleeding may cause extensive damage to the synovia by deposition of iron and subsequent chronic inflammation. This causes pain, swelling and instability of the joint, predisposing it to further bleeding and ultimate
estimated that approximately 70% of patients with haemophilia worldwide do not receive adequate treatment. This is associated with an enormous burden of musculoskeletal morbidity and decreased life expectancy.11
Treatment complications The most challenging complication is the formation of inhibiting antibodies (inhibitors) directed against active parts of the FVIII or FIX protein, thereby decreasing its coagulant activity. Inhibitors occur in about 25% of the patients with haemophilia A and are rare in haemophilia B. They usually arise in young children within the first 50 treatment days and increase the bleeding tendency, as they render the treatment with FVIII concentrates ineffective. Bleeding episodes in inhibitor patients can be prevented or treated with agents that can evoke clot formation in the absence of FVIII or FIX, such as recombinant FVIIa (Novoseven®
activated prothrombin complex (FEIBA®
).12 To eradicate the inhibitors,
patients are treated with a regimen called Immune Tolerance Induction. This regimen consists of frequent administration (daily to three times per week) of high doses of FVIII.13
“Regular administration of clotting factor concentrates is required to prevent bleedings and concomitant joint impairment in patients with the severe form of haemophilia”
development of arthropathy: painful joint deformation with limited function. To prevent haemarthros, prophylactic administration of FVIII or FIX concentrate 2–3 times a week is considered the standard of care for patients with severe haemophilia A or B who live in countries where this is economically feasible, according to a recent UK guideline.10
Patients with 10
moderate or mild haemophilia are generally treated on demand, that is to say, only when bleeding occurs. Most patients with severe haemophilia infuse themselves intravenously at home. This has greatly improved their health- related quality of life and reduced medical costs. In developing countries, the availability of clotting factors concentrates is limited, due to restricted financial resources. It is
Allergic reactions to clotting factor concentrates are extremely rare, as current concentrates are of very high purity. However, occasional severe anaphylactic reactions may be observed after administration of FIX concentrates in patients with FIX inhibitors. In the 1980s, all clotting factor concentrates were derived from large pools of blood donor plasma. This facilitated transmission of blood-borne viruses such as hepatitis B and C and HIV, when untested blood from unscreened donors was used, with devastating consequences. Presently, the plasma clotting factor concentrates are considered safe with regard to transmission of these viruses, as donors are tested extensively prior to blood donation and viral inactivating procedures are performed.
Haemophilia is a hereditary X-linked clotting disorder that can be treated safely and effectively by infusion of clotting factor concentrates. Regular administration of clotting factor concentrates is required to prevent bleedings and concomitant joint impairment in patients with the severe form of haemophilia (FVIII/FIX < 0.01 IU/ml). In emergency trauma situations, immediate administration of clotting factor concentrates is necessary. l
References 1. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012;379:1447–56.
2. Fijnvandraat K, Cnossen MC, Leebeek FWG, Peters M. Diagnosis and management of haemophilia. Br Med J 2012;344:e2707.
3. Lenting PJ, van Mourik JA, Mertens K. The life cycle of coagulation factor VIII in view of its structure and function. Blood 1998;92(11):3983–96.
4. White GC et al. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001;85(3):560.
5. The Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTERS) at http://hadb.org.uk/
6. Hemophilia B mutation database at http://www. kcl.ac.uk/ip/petergreen/haemBdatabase.html
7. CDC Hemophilia A Mutation Project (CHAMP) at http://www.cdc.gov/ncbddd/hemophilia/ champs.ht
8. Plug I et al. Bleeding in carriers of hemophilia. Blood 2006;108(1):52–6.
9. Keeling D, Tait C, Makris M. Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. A United Kingdom Haemophilia Center Doctors’ Organisation (UKHCDO) guideline approved by the British Committee for Standards in Haematology. Haemophilia 2008;14(4):671–84.
10. Richards M et al. A United Kingdom Haemophilia Centre Doctors’ Organization guideline approved by the British Committee for Standards in Haematology: guideline on the use of prophylactic factor VIII concentrate in children and adults with severe haemophilia A. Br J Haematol 2010;149(4):498–507.
11. Srivastava A et al. Hemophilia treatment in developing countries: products and protocols. Semin Thromb Hemost 2005;31(5):495–500.
12. Leissinger C et al. Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors. N Engl J Med 2011;365(18):1684–92.
13. Hay CR, Dimichele DM. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood 2011;119(6):1335–44.
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