Semin Thromb Hemost 2009; 35(8): 820-826
DOI: 10.1055/s-0029-1245115
© Thieme Medical Publishers

Management of Hemophilia in Patients with Inhibitors: The Perspective from Developing Countries

Vikram Mathews1 , Sukesh C. Nair1 , Sachin David1 , Auro Viswabandya1 , Alok Srivastava1
  • 1Department of Hematology, Christian Medical College, Vellore, India
Further Information

Publication History

Publication Date:
18 February 2010 (online)

ABSTRACT

Data are limited on inhibitors in people with hemophilia (PWH) in developing countries. There is a perception that the overall prevalence of inhibitors, ranging from 7 to 19% in different reports, may be lower in these countries as compared with that reported from developed countries. This is possible given the fact that most patients are treated after 2 years of age with plasma-derived clotting factor concentrates. Whether genetic or other environmental factors also contribute to this needs further evaluation. There is a need to develop laboratory infrastructure and establish quality control programs for laboratory tests for inhibitors in developing countries. Management options vary widely given the socioeconomic diversity among these countries. Significant individualization of approach to management is therefore required depending on the available resources, particularly with regard to the use of bypassing agents. The limited data on immune tolerance induction with some low-dose regimens deserve further evaluation. Even in resource-constrained environments, education and a policy of systematic screening of patients associated with judicious use of bypassing agents can significantly improve the care of PWH who develop inhibitors.

REFERENCES

  • 1 Key N S. Inhibitors in congenital coagulation disorders.  Br J Haematol. 2004;  127(4) 379-391
  • 2 Ghosh K, Shetty S, Kulkarni B et al.. Development of inhibitors in patients with haemophilia from India.  Haemophilia. 2001;  7(3) 273-278
  • 3 Srivastava A, Mathews V, Jacob R et al.. Prevalence of inhibitors in patients with severe hemophilia A in India. [abstract].  Haemophilia. 2008;  14(Suppl 2) 56
  • 4 Chalmers E A, Brown S A, Keeling D Paediatric Working Party of UKHCDO et al. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A.  Haemophilia. 2007;  13(2) 149-155
  • 5 Gouw S C, van der Bom J G, Marijke van den Berg H. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study.  Blood. 2007;  109(11) 4648-4654
  • 6 Goudemand J, Rothschild C, Demiguel V FVIII-LFB and Recombinant FVIII study groups et al. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A.  Blood. 2006;  107(1) 46-51
  • 7 Viel K R, Ameri A, Abshire T C et al.. Inhibitors of factor VIII in black patients with hemophilia.  N Engl J Med. 2009;  360(16) 1618-1627
  • 8 Santagostino E, Mancuso M E, Rocino A et al.. Environmental risk factors for inhibitor development in children with haemophilia A: a case-control study.  Br J Haematol. 2005;  130(3) 422-427
  • 9 Gouw S C, van der Bom J G, Auerswald G, Ettinghausen C E, Tedgård U, van den Berg H M. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study.  Blood. 2007;  109(11) 4693-4697
  • 10 Iorio A, Marucci M, Mareschesisni P, Manucci M. Plasma derived and recombinant factor VIII concentrates induce a different rate of inhibitor development in hemophilia A patients. A systematic review of the literature.  J Thromb Haemost. 2009;  7 , Abstract OC-MO-035
  • 11 Kavakli K, Gringeri A, Bader R, Nisli G, Polat A, Aydinok Y. Inhibitor development and substitution therapy in a developing country: Turkey.  Haemophilia. 1998;  4(2) 104-108
  • 12 Saint-Remy J M, Lacroix-Desmazes S, Oldenburg J. Inhibitors in haemophilia: pathophysiology.  Haemophilia. 2004;  10(suppl 4) 146-151
  • 13 Oldenburg J, Brackmann H H, Schwaab R. Risk factors for inhibitor development in hemophilia A.  Haematologica. 2000;  85(10, suppl) 7-13 discussion 13-14
  • 14 Leiria L B, Roisenberg I, Salzano F M, Bandinelli E. Introns 1 and 22 inversions and factor VIII inhibitors in patients with severe haemophilia A in southern Brazil.  Haemophilia. 2009;  15(1) 309-313
  • 15 Rastegar Lari G, Enayat M S, Arjang Z, Lavergne J M, Ala F. Identification of intron 1 and 22 inversion mutations in the factor VIII gene of 124 Iranian families with severe haemophilia A.  Haemophilia. 2004;  10(4) 410-411
  • 16 Astermark J, Oldenburg J, Pavlova A, Berntorp E, Lefvert A K. MIBS Study Group . Polymorphisms in the IL10 but not in the IL1beta and IL4 genes are associated with inhibitor development in patients with hemophilia A.  Blood. 2006;  107(8) 3167-3172
  • 17 Astermark J, Oldenburg J, Carlson J et al.. Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A.  Blood. 2006;  108(12) 3739-3745
  • 18 ter Avest P C, Fischer K, Mancuso M E CANAL Study Group et al. Risk stratification for inhibitor development at first treatment for severe hemophilia A: a tool for clinical practice.  J Thromb Haemost. 2008;  6(12) 2048-2054
  • 19 Hay C R, Brown S, Collins P W, Keeling D M, Liesner R. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors' Organisation.  Br J Haematol. 2006;  133(6) 591-605
  • 20 Ewing N P, Kasper C K. In vitro detection of mild inhibitors to factor VIII in hemophilia.  Am J Clin Pathol. 1982;  77(6) 749-752
  • 21 Mammen J, Nair S C, Srivastava A. External quality assessment scheme for hemostasis in India.  Semin Thromb Hemost. 2007;  33(3) 265-272
  • 22 Ling M, Duncan E M, Rodgers S E, Street A M, Lloyd J V. Low detection rate of antibodies to non-functional epitopes on factor VIII in patients with hemophilia A and negative for inhibitors by Bethesda assay.  J Thromb Haemost. 2003;  1(12) 2548-2553
  • 23 Sahud M A, Pratt K P, Zhukov O, Qu K, Thompson A R. ELISA system for detection of immune responses to FVIII: a study of 246 samples and correlation with the Bethesda assay.  Haemophilia. 2007;  13(3) 317-322
  • 24 Kempton C L, White II G C. How we treat a hemophilia A patient with a factor VIII inhibitor.  Blood. 2009;  113(1) 11-17
  • 25 Pérez Bianco R, Ozelo M C, Villaça P R et al.. Diagnosis and treatment of congenital hemophilia with inhibitors: a Latin American perspective.  Medicina (B Aires). 2008;  68(3) 227-242
  • 26 Ozelo M C, Villaça P R, De Almeida J O et al.. A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil.  Haemophilia. 2007;  13(5) 462-469
  • 27 You C W, Lee S Y, Park S K. Cost and effectiveness of treatments for mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Korea.  Haemophilia. 2009;  15(1) 217-226
  • 28 McMillan C W, Shapiro S S, Whitehurst D, Hoyer L W, Rao A V, Lazerson J. The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors.  Blood. 1988;  71(2) 344-348
  • 29 El Alfy M S, Tantawy A A, Ahmed M H, Abdin I A. Frequency of inhibitor development in severe haemophilia A children treated with cryoprecipitate and low-dose immune tolerance induction.  Haemophilia. 2000;  6(6) 635-638
  • 30 Unuvar A, Kavakli K, Baytan B et al.. Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors.  Haemophilia. 2008;  14(2) 315-322
  • 31 Preston F E, Dinsdale R C, Sutcliffe D J, Bardhan G, Wyld P J, Hamlyn J F. Factor VIII inhibitor by-passing activity (FEIBA) in the management of patients with factor VIII inhibitors.  Thromb Res. 1977;  11(5) 643-651
  • 32 Rasche H, Bindewald H, Köhle W, Scheck R, Heinrich R, Seibert K. Emergency treatment of haemophilia A with factor VIII inhibitors using activated prothrombin complex concentrates [author's translation].  Dtsch Med Wochenschr. 1977;  102(9) 319-323
  • 33 Thomas T, Williams H, Williams Y, Hunt J. FEIBA in haemophiliacs with factor VIII inhibitor.  BMJ. 1977;  1(6052) 52
  • 34 Negrier C, Goudemand J, Sultan Y, Bertrand M, Rothschild C, Lauroua P. Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity.  Thromb Haemost. 1997;  77(6) 1113-1119
  • 35 Bhave A, Srivastava A, Lee V et al.. Low-dose activated factor IX complex concentrates (FEIBA) for postoperative haemostasis in a patient with high responding factor VIII inhibitors.  Haemophilia. 1995;  1 274-276
  • 36 Mathews V, Viswabandya A, Baidya S et al.. Surgery for hemophilia in developing countries.  Semin Thromb Hemost. 2005;  31(5) 538-543
  • 37 Mahasandana C, Patharathienskul D, Suvatte V. Hemophilia with factor VIII and factor IX inhibitors: incidence, bleeding problems and management.  Southeast Asian J Trop Med Public Health. 1993;  24(suppl 1) 106-112
  • 38 Modaresi A R, Torghabeh H M, Pourfathollah A A, Shooshtari M M, Yazdi Z R. Pattern of factor VIII inhibitors in patients with hemophilia A in the north east of Iran.  Hematology. 2006;  11(3) 215-217
  • 39 Pérez Bianco R, Ozelo M C, Villaça P R et al.. Diagnosis and treatment of congenital hemophilia with inhibitors: a Latin American perspective.  Medicina (B Aires). 2008;  68(3) 227-242
  • 40 Rezende S M, Pinheiro K, Caram C, Genovez G, Barca D. Registry of inherited coagulopathies in Brazil: first report.  Haemophilia. 2009;  15(1) 142-149

Alok SrivastavaM.D. F.R.A.C.P. F.R.C.P.A. F.R.C.P. 

Department of Hematology, Christian Medical College

Vellore 632004, India

Email: aloks@cmcvellore.ac.in

    >