Asian Journal of Transfusion Science
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COMMENTARY Table of Contents   
Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 6-7
Transfusion related complications in hemophilia


Department of Transfusion Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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Date of Web Publication2-Feb-2013
 

How to cite this article:
Marwaha N. Transfusion related complications in hemophilia. Asian J Transfus Sci 2013;7:6-7

How to cite this URL:
Marwaha N. Transfusion related complications in hemophilia. Asian J Transfus Sci [serial online] 2013 [cited 2021 Dec 7];7:6-7. Available from: https://www.ajts.org/text.asp?2013/7/1/6/106713


Hemophilia is a hereditary coagulation disorder due to either deficiency of coagulation FVIII (hemophilia A) or of FIX (hemophilia B). There is no ethnic or geographic prevalence and hemophilia A occurs at a frequency of 1 in 5000 live male births and hemophilia B at a frequency of 1 in 30000. [1] Clinically both the deficiencies present as a lifelong bleeding disorder with considerable morbidity due to crippling arthropathy. The clinical severity is determined by the baseline levels of FVIII/FIX. In severe disease the factor levels are less than 1% or 0.01u/ml. In moderate disease the factor levels range from 1% to 5% (0.01-0.05u/ml) while mild hemophiliacs have factor levels ranging from more than 5-30% (>0.05-0.3u/ml). Hemophilia A and B can only be distinguished on the basis of coagulation FVIII or IX assays. [2]

Replacement of the deficient factor is the mainstay of treatment; it may be "on demand" when the factor is administered during a bleeding episode, or "prophylactic" when infused as a regular regimen to prevent hemarthroses in severe deficiency. The evolution of replacement therapy in persons with hemophila (PWH) parallels the advances and challenges in transfusion medicine. In the 1950s fresh frozen plasma (FFP) was the only product available, other than whole blood and adequate dosing was limited by the volume required to be transfused. Cryoprecipitate became available in the 1960s for hemophilia A patients. A decade later plasma-derived factor concentrates heralded the era of modern management of the disease. [3] The initial results with factor concentrates were so gratifying that it resulted in widespread use. Then emerged the tragic consequences of HBV, HIV, and HCV transmission. Viral inactivation procedures were intensified and the 1990s saw availability of recombinant factors VIII and IX. The replacement therapy in hemophilia in the developed world reached an acceptable level of safety from transfusion transmissible infections.

However, repeated infusions with FVIII concentrates have led to development of neutralizing antibodies or inhibitors which further complicates the management. The cumulative incidence of inhibitors [4] in patients with hemophilia A and B is 25-32% and 4-5%, respectively, with prevalence around 12% and <4%. Early exposure to FVIII concentrates has been suggested as one of the significant predisposing factor. [5] In a study from Turkey the risk of inhibitor development in PWH treated with FFP was 0% versus 30% in patients infused with FVIII concentrates. [6] Management of PWH with inhibitors in resource replete countries involves one of the two options; either high-dose FVIII concentrates with immune suppression or FVIII bypassing agents (prothrombin complex concentrates, rFVIIa), both options being readily accessible.

Contrast this with the scenario in developing countries where almost 80% of the world's PWH live with access to only 20% of the therapeutic resources. In India with a population of 1.2 billion, the number of expected PWH would be approximately 120000. However, as per data from World Federation of Hemophilia Global Survey 2010 [7] the number of registered PWH in India is only 13993. This indicates gross underdiagnosis, early deaths, and lack of awareness to access treatment facilities. Transfusion options still include whole blood and FFP. Cryoprecipitate is available in select few blood centers. FVIII/FIX concentrates are beyond the affordable reach of most of the patients, despite efforts made by Hemophila Federation of India to provide FVIII/IX concentrates at subsidized cost. Minor bleeds have also been controlled with antifibrinolytic agents. [8] Data on management related complications is scarce with the first study being reported by Ghosh et al. in 2001 on development of inhibitors in PWH. 8.2% of patients with severe hemophilia A developed inhibitors. [9] In another study inhibitor prevalence was 13%. [10] In the study by Dubey et al., in this issue of the journal, the inhibitor prevalence is only 5.1%. [11] The data from all the three Indian studies shows lower inhibitor prevalence as compared with recent data from developed countries but is comparable with earlier reports prior to initiation of intensive FVIII concentrate replacement therapy. [12],[13] The TTI seroreactivity in PWH is a cause for concern. Dependence on blood bank products released after serological screening does pose a risk for window period transmission. Phase wise implementation of viral nucleic acid testing and/or virus inactivation and sterile filtration of plasma and cryoprecipitate will be of tremendous value in achieving transfusion safety. Adequate and affordable availability of FVIII/FIX concentrates will depend upon indigenous production of factor concentrates. Presently there is no such setup for production of plasma derived or recombinant FVIII/FIX concentrates in the country. Alloimmunisation is a small but significant risk in PWH in developing countries where whole blood transfusions may be the only replacement option. Secondly patients present late in the course of bleeding, may become anemic and require red cell transfusions.

Dubey et al. [11] have rightfully suggested that the real magnitude of the problem is unclear in their region of study. The situation is similar throughout the country; exact burden of the disease is still unknown, diagnostic and therapeutic centers are few and beyond the reach of many patients. Risk stratification for complications may differ between PWH on FFP and cryoprecipitate therapy versus those on factor concentrates replacement, as the availability of the latter increases. What PWH require is comprehensive care from a multidisciplinary team. Presently the HF1 with its state and city chapters has made perceptible commendable attempts in care for PWH. Consequent upon successful public interest litigations few state governments are making factor concentrates available either free of cost or at markedly subsidized cost. All efforts, though well meaning and appreciable are still insufficient towards the basic goal of comprehensive care. Departments of hematology and transfusion medicine could definitely serve to act as nodal centers for diagnosis and management but adequate governmental support is essential to provide hemophilia care in an organized manner.

 
   References Top

1.Brinkhous KM. A Short History of Hemophilia. In: Brinkhous KM, Hemker HC, editors. Hand book of Hemophilia. 1 st ed. New York: Elsevier; 1975. p.3.  Back to cited text no. 1
    
2.Roberts HR, Escobar M, White GC. Hemophilia A and Hemophilia B. In: Lichtman MA, Beutler E, Kipps TJ, Seligson U, Kaushansky J, Prchal JT, editors. Williams Hematology. 7 th ed. New York: McGraw Hill; 2006. p.1867-86.  Back to cited text no. 2
    
3.DiMichele D. Hemophilia 1996. New approach to an old disease. Pediatr Clin North Am 1996;43:709-36.  Back to cited text no. 3
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4.Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol 2004;127:379-91.  Back to cited text no. 4
[PUBMED]    
5.Gouw SC, van der Bom JG, Auerswald G, Ettinghausen CE, Tedgård U, van den Berg HM. 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;109:4693-7.  Back to cited text no. 5
    
6.Kavakli K, Gringeri A, Bader R, Nisli G, Polat A, Aydinok Y. Inhibitor development and substitution therapy in a developing country: Turkey. Haemophilia 1998;4:104-8.  Back to cited text no. 6
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7.World Federation of Hemophilia. Global Survey 2010. Available from: www.wfh.org. [Last accessed on 2012 Nov 1].  Back to cited text no. 7
    
8.Ghosh K, Shetty S, Sahu D. Haemophilia care in India: Innovations and integrations by various chapters of Haemophilia Federation of India (HFI). Haemophilia 2010;16:61-5.  Back to cited text no. 8
    
9.Ghosh K, Shetty S, Kulkarni B, Nair S, Pawar A, Khare A, et al. Development of inhibitors in patients with haemophilia from India. Haemophilia 2001;7:273-8.  Back to cited text no. 9
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10.Mathews V, Nair SC, David S, Viswabandya A, Srivastava A. Management of hemophilia in patients with inhibitors: The perspective from developing countries. Semin Thromb Hemost 2009;35:820-6.  Back to cited text no. 10
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11.Dubey A, Verma A, Elhence P, Sonker A, Agarwal P. Evaluation of transfusion-related complications along with estimation of inhibitors in patients with hemophilia A: A pilot study from a single center. Asian J Transfus Sci 2013;7:8-10.  Back to cited text no. 11
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12.Sultan Y. Prevalence of inhibitors in a population of 3435 hemophilia patients in France. French Hemophilia Study Group. Thromb Haemost 1992;67:600-2.  Back to cited text no. 12
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13.McMillan CW, Shapiro SS, Whitehurst D, Hoyer LW, Rao AV, 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;71:344-8.  Back to cited text no. 13
    

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Correspondence Address:
Neelam Marwaha
Department of Transfusion Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


PMID: 23559755

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2006 - Asian Journal of Transfusion Science | Published by Wolters Kluwer - Medknow
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