Treatment of Haemophilia A by Replacement Therapy using Factor VIII Inhibitors

Authors(2) :-Maria Shahid, Sikander Ali

Haemophilia A is a very severe disease which is caused due to deficiency of a protein clotting factor VIII. Haemophilia A is X-linked recessive disorder which can be treated by the replacement therapy or by development of an inhibitors or antibodies against the FVIII. Hemarthroses is a disease in which bleeding in the joint spaces occur. This disease occurs approximately 70 to 80% in haemophilic patients. Then here we review about the epidimicity that deals with the transformation of haemophilia A. Then the process of inhibition stated, in which under the influence of some chemical substances the specific chemical process may inhibit. So, different replacement therapy may be ineffective when an inhibitor affect the factor VIII gene. In the end here stated different treatments for the management & control of disease, so among them the counselling between physician & patient is very effective.

Authors and Affiliations

Maria Shahid
Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan
Sikander Ali
Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan

Hemarthroses, Haemophilia, Epidimicity, Epidemiology, DNA, AVD, IgG, TCR, Arthropathy, Prophylaxis

  1. André, S., Y. Meslier, J.D. Dimitrov, Y. Repessé, S.V. Kaveri and S. Lacroix- Desmazes, et al. A cellular viewpoint of anti-FVIII immune response in haemophilia A. Clin. Rev. Allergy Immunol., 37(2): 105-113.
  2. Astermark, J. 2010. Inhibitor development: patient-determined risk factors of Haemophilia. 16(102): 66-70.
  3. Astermark, J., E. Berntorp, G.C. White, B.L. Kroner. MIBS Study Group. The Malmö International Brother Study (MIBS): further support forgenetic predisposition to inhibitor development in haemophilia patients. Haemophilia, 7(3): 267-272.
  4. Castaldo, G., V. Argenio, P. Nardiello, F. Zarrilli, V. Sanna, A. Rocino, et al. Haemophilia A: molecular insights. Clin. Chem. Lab. Med., 45(4): 450-461.
  5. Centers for Disease Control and Prevention (CDC). 2010 HIV transmission through transfusion – Missouri and Colorado, 2008. MMWR Morb. Mortal Wkly Rep., 59(41): 1335–1339.
  6. Chaves, D.G. and C.V. Rodrigues. Development of factor VIII inhibitors in haemophilia A. Rev. Bras. Hematol. Hemoter., 31(5): 384-390.
  7. Chorba, T.L., R.C. Holman, M.J. Clarke, B.L. Evatt. Effects of HIV infection on age and cause of death for persons with haemophilia A in the United States. Am. J. Hematol., 66(4): 229-240.
  8. Chorba, T.L., R.C. Holman, T.W. Strine, M.J. Clarke, B.L. Evatt. 1994. Changes in longevity and causes of death among persons with haemophilia A. J. Hematol., 45(2): 112-121.
  9. DiMichele, D., E.J. Neufeld. Haemophilia. A new approach to an old disease. Hematol. Oncol. Clin. North Am., 12(6): 1315-1344.
  10. Geraghty, S., T. Dunkley, C. Harrington, K. Lindvall, J. Maahs, J. Sek. Practice patterns in haemophilia, A therapy - global progress towards optimal care. Haemophilia, 12(1): 75-81.
  11. Ghosh, K., S. Shetty. Immune response to FVIII in haemophilia A Review of risk factors. Clin. Rev. Allergy Immunol., 37(2): 58-66.
  12. Gill, J.C. The role of genetics in inhibitor formation. Thromb. Haemost., 82(2): 500-504.
  13. Gitschier, J., W.I. Wood, T.M. Goralka, K.L. Wion, E.Y. Chen, D.H. Eaton, et al. Characterization of the human factor VIII gene. Nature, 312: 326-330.
  14. Gouw, S.C., H.M. van den Berg, J. Oldenburg, J. Astermark, P.G. de Groot, M. Margaglione. et al. F8 gene mutation type and inhibitor development in patients with severe haemophilia A: systematic review and metaanalysis. Blood, 119(12): 2922-2934.
  15. Hoyer, L.W. The incidence of factor VIII inhibitors in patients with severe haemophilia A. Adv. Exp. Med. Biol., 386: 35-45.
  16. Lenting, P.J., J.W. van de Loo, M.J. Donath, J.A. van Mourik, K. Mertens, 1996. The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a binding site for activated factor IX. J Biol Chem, 271(4): 1935-1940.
  17. Lusher, J.M. Early treatment with recombinant factor VII a results in greater efficacy with less product. Eur. J. Haematol. Suppl., 63: 7-10.
  18. Oldenburg, J., A. Pavlova. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia, 12: 15-22.
  19. Parameswaran, R., A.D. Shapiro, J.C. Gill, C.M. Kessler. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Haemophilia and Thrombosis Research Society Registry. Haemophilia, 11(2): 100-106.
  20. Pratt, K.P., A.R. Thompson. B-cell and T-cell epitopes in anti-factor VIII immune responses. Clin Rev Allergy Immunol., 37(2): 80-95.
  21. Scandella, D., C. Kessler, P. Esmon, D. Hurst, S. Courter, E. Gomperts. et al. Epitope specificity and functional characterization of factor VIII inhibitors. Adv. Exp. Med. Biol., 386: 47-63.
  22. Scandella, D., M. Mattingly, S. Graaf, C.A. Fulcher. 1989. Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization. Blood, 74(5): 1618-1626.
  23. Shen, B.W., P.C. Spiegel, C.H. Chang, J.W. Huh, J.S. Lee, J. Kim, et al. The tertiary structure and domain organization of coagulation factor VIII. Blood, 111(3): 1240-1247.
  24. Soares, R.P., D.A. Chamone, S.P. Bydlowski. 2001. Factor VIII gene inversions and polymorphisms in Brazilian patients with haemophilia A: carrier detection and prenatal diagnosis. Haemophilia, 7(3): 299-305.
  25. Soucie, J.M., R. Nuss, B. Evatt. et al. Mortality among males with haemophilia: relations with source of medical care. Blood, 96(2): 437-442.
  26. Tencer, T., H.S. Friedman, J. Li-McLeod, K. Johnson. Medical costs and resource utilization for haemophilia patients with and without HIV or HCV infection. J. Manag. Care Pharm., 13(9): 790-798.
  27. Tuddenham, E.G., R. Schwaab, J. Seehafer, et al. Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene, second edition. Nucleic Acids Res., 22(22): 4851-4868.
  28. Tullis, J.L., M. Melin, P. Jurigian. Clinical use of human prothrombin complexes. N Engl. J. Med., 273(13): 667-674.
  29. Wight, J. and S. Paisley. 2003. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia, 9(4): 418-435.

Publication Details

Published in : Volume 2 | Issue 4 | July-August 2016
Date of Publication : 2016-08-30
License:  This work is licensed under a Creative Commons Attribution 4.0 International License.
Page(s) : 155-161
Manuscript Number : IJSRST162422
Publisher : Technoscience Academy

Print ISSN : 2395-6011, Online ISSN : 2395-602X

Cite This Article :

Maria Shahid, Sikander Ali, " Treatment of Haemophilia A by Replacement Therapy using Factor VIII Inhibitors", International Journal of Scientific Research in Science and Technology(IJSRST), Print ISSN : 2395-6011, Online ISSN : 2395-602X, Volume 2, Issue 4, pp.155-161, July-August-2016.
Journal URL :

Article Preview