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Semin Thromb Hemost 2013; 39(07): 779-793
DOI: 10.1055/s-0033-1354420
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pathogen Safety of Long-Term Treatments for Bleeding Disorders: (Un)Predictable Risks and Evolving Threats

Giovanni Di Minno
1   Department of Clinical Medicine and Surgery, Regional Reference Centre for Coagulation Disorders, Napoli, Italy
,
Mariana Canaro
2   Department of Hemostasis and Thrombosis, Son Espases Universitary Hospital, Palma de Mallorca, Spain
,
James W. Ironside
3   National Creutzfeldt-Jakob Disease Surveillance Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
,
David Navarro
4   Department of Microbiology, Microbiology Service, Hospital Clínico Universitario, School of Medicine, University of Valencia, Valencia, Spain
,
Carlo F. Perno
5   Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
,
Andreas Tiede
6   Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
,
Lutz Guertler
7   Max von Pettenkofer Institute for Hygiene and Medical Microbiology, University of München, Munich, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
12 September 2013 (online)

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Pathogen Safety of Long-Term Treatments for Bleeding Disorders: (Un)Predictable Risks and Evolving ThreatsSemin Thromb Hemost 2013; 39(08): 973-973
DOI: 10.1055/s-0033-1358798

Abstract

Substantial improvements in the safety of blood and plasma products for the management of bleeding disorders have been achieved in recent decades. This has led some clinicians to believe that the infectious threat is over and that inhibitor formation is the foremost complication of hemophilia therapy. On the contrary, elimination of all microbes from blood is difficult, potentially impossible, and there are always threats from emerging pathogens. The risk of infection transmission is also increasing due to greater exposure to products, increasing prophylaxis and high-dose regimens for immune tolerance, and longevity of hemophilia patients. Current products can be considered “reasonably safe,” but pathogen testing is not all-inclusive, and manufacturing and purification techniques are often not standardized. Although safer nonplasma-derived products are widely used, they are not available for all bleeding disorders, and so there is an ongoing need for plasma-derived products. This review will discuss the evolving risk from emerging pathogens in the context of the issues described. Reducing the risk from emerging infections requires global collaboration to devise ways to monitor and continue to improve blood safety.

Keywords

bleeding disorders - blood safety - emerging infectious agent(s)
 

  • References

  • 1 Srivastava A, Brewer AK, Mauser-Bunschoten EP , et al; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (1) e1-e47
    CrossrefPubMedGoogle Scholar
  • 2 Miller CH, Benson J, Ellingsen D , et al; Hemophilia Inhibitor Research Study Investigators. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia 2012; 18 (3) 375-382
    CrossrefPubMedGoogle Scholar
  • 3 Schwarz J, Astermark J, Menius ED , et al; Hemophilia Inhibitor Genetics Study Combined Cohort. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Haemophilia 2013; 19 (1) 113-118
    CrossrefPubMedGoogle Scholar
  • 4 Lippi G, Favaloro EJ, Montagnana M, Manzato F, Guidi GC, Franchini M. Inherited and acquired factor V deficiency. Blood Coagul Fibrinolysis 2011; 22 (3) 160-166
    CrossrefPubMedGoogle Scholar
  • 5 Kessler CM. New perspectives in hemophilia treatment. Hematology (Am Soc Hematol Educ Program) 2005; 429-435
    PubMedGoogle Scholar
  • 6 Brooker M. Registry of Clotting Factor Concentrates. 9th ed. Montreal, Quebec, Canada: World Federation of Hemophilia (WFH); ; 2012. http://www1.wfh.org/publications/files/pdf-1227.pdf . Accessed May 1, 2013
    Google Scholar
  • 7 Franchini M, Mannucci PM. Past, present and future of hemophilia: a narrative review. Orphanet J Rare Dis 2012; 7 (1) 24
    CrossrefPubMedGoogle Scholar
  • 8 Tagliaferri A, Rivolta GF, Iorio A , et al; Italian Association of Hemophilia Centers. Mortality and causes of death in Italian persons with haemophilia, 1990-2007. Haemophilia 2010; 16 (3) 437-446
    PubMedGoogle Scholar
  • 9 Chorba TL, Holman RC, Clarke MJ, Evatt BL. Effects of HIV infection on age and cause of death for persons with hemophilia A in the United States. Am J Hematol 2001; 66 (4) 229-240
    CrossrefPubMedGoogle Scholar
  • 10 Plug I, Van Der Bom JG, Peters M , et al. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost 2006; 4 (3) 510-516
    CrossrefPubMedGoogle Scholar
  • 11 Darby SC, Kan SW, Spooner RJ , et al; UK Haemophilia Centre Doctors' Organisation. The impact of HIV on mortality rates in the complete UK haemophilia population. AIDS 2004; 18 (3) 525-533
    CrossrefPubMedGoogle Scholar
  • 12 Fransen van de Putte DE, Fischer K, Pulles AE , et al. Non-fatal cardiovascular disease, malignancies, and other co-morbidity in adult haemophilia patients. Thromb Res 2012; 130 (2) 157-162
    CrossrefPubMedGoogle Scholar
  • 13 Yee TT, Lee CA. Transfusion-transmitted infection in hemophilia in developing countries. Semin Thromb Hemost 2005; 31 (5) 527-537
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Branch AD, Van Natta ML, Vachon ML, Dieterich DT, Meinert CL, Jabs DA ; Studies of the Ocular Complications of AIDS Research Group. Mortality in hepatitis C virus-infected patients with a diagnosis of AIDS in the era of combination antiretroviral therapy. Clin Infect Dis 2012; 55 (1) 137-144
    CrossrefPubMedGoogle Scholar
  • 15 Franchini M, Tagliaferri A, Mengoli C, Cruciani M. Cumulative inhibitor incidence in previously untreated patients with severe hemophilia A treated with plasma-derived versus recombinant factor VIII concentrates: a critical systematic review. Crit Rev Oncol Hematol 2012; 81 (1) 82-93
    CrossrefPubMedGoogle Scholar
  • 16 Goedert JJ, Chen BE, Preiss L, Aledort LM, Rosenberg PS. Reconstruction of the hepatitis C virus epidemic in the US hemophilia population, 1940-1990. Am J Epidemiol 2007; 165 (12) 1443-1453
    CrossrefPubMedGoogle Scholar
  • 17 Svicher V, Cento V, Bernassola M , et al. Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection. Antiviral Res 2012; 93 (1) 86-93
    CrossrefPubMedGoogle Scholar
  • 18 Powell JS. Recombinant factor VIII in the management of hemophilia A: current use and future promise. Ther Clin Risk Manag 2009; 5 (2) 391-402
    PubMedGoogle Scholar
  • 19 Sharma S, Sharma P, Tyler LN. Transfusion of blood and blood products: indications and complications. Am Fam Physician 2011; 83 (6) 719-724
    PubMedGoogle Scholar
  • 20 Wagner S. Transfusion-related bacterial sepsis. Curr Opin Hematol 1997; 4 (6) 464-469
    CrossrefPubMedGoogle Scholar
  • 21 Pittman M. A study of bacteria implicated in transfusion reactions and of bacteria isolated from blood products. J Lab Clin Med 1953; 42 (2) 273-288
    PubMedGoogle Scholar
  • 22 Goel R, Krishnamurti L. Mortality, health care utilization and associated diagnoses in hospitalized patients with haemophilia in the United States: first reported nationwide estimates. Haemophilia 2012; 18 (5) 688-692
    CrossrefPubMedGoogle Scholar
  • 23 Rothschild C, D'Oiron R, Borel-Derlon A , et al. Use of Haemate(®) P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: a multicentre observational study. Haemophilia 2013; 19 (2) 281-286
    CrossrefPubMedGoogle Scholar
  • 24 DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol 2007; 138 (3) 305-315
    CrossrefPubMedGoogle Scholar
  • 25 Ghosh K, Shetty S. Immune response to FVIII in hemophilia A: an overview of risk factors. Clin Rev Allergy Immunol 2009; 37 (2) 58-66
    CrossrefPubMedGoogle Scholar
  • 26 Makris M, Hay CR, Gringeri A, D'Oiron R. How I treat inhibitors in haemophilia. Haemophilia 2012; 18 (Suppl. 04) 48-53
    CrossrefPubMedGoogle Scholar
  • 27 Iorio A, Halimeh S, Holzhauer S , et al. Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review. J Thromb Haemost 2010; 8 (6) 1256-1265
    CrossrefPubMedGoogle Scholar
  • 28 Mannucci PM, Mancuso ME, Santagostino E. How we choose factor VIII to treat hemophilia. Blood 2012; 119 (18) 4108-4114
    CrossrefPubMedGoogle Scholar
  • 29 Ghio M, Contini P, Ottonello L , et al. Effect of clotting factors concentrates on lymphocyte and neutrophil function in vitro. Thromb Haemost 2003; 89 (2) 365-373
    PubMedGoogle Scholar
  • 30 Franchini M. Plasma-derived versus recombinant Factor VIII concentrates for the treatment of haemophilia A: recombinant is better. Blood Transfus 2010; 8 (4) 292-296
    PubMedGoogle Scholar
  • 31 Goodnough LT, Shander A, Brecher ME. Transfusion medicine: looking to the future. Lancet 2003; 361 (9352) 161-169
    CrossrefPubMedGoogle Scholar
  • 32 Ceccherini-Nelli L, Filipponi F, Mosca F, Campa M. The risk of contracting an infectious disease from blood transfusion. Transplant Proc 2004; 36 (3) 680-682
    CrossrefPubMedGoogle Scholar
  • 33 Glynn SA, Busch MP, Dodd RY , et al. Emerging infectious agents and the nation's blood supply: responding to potential threats in the 21st century. Transfusion 2013; 53 (2) 438-454
    CrossrefPubMedGoogle Scholar
  • 34 Trimble SR, Parker CS, Grant AM, Soucie JM, Reyes N. Assessing emerging infectious threats to blood safety for the blood disorders community. Am J Prev Med 2010; 38 (4, Suppl): S468-S474
    CrossrefPubMedGoogle Scholar
  • 35 Webby R, Hoffmann E, Webster R. Molecular constraints to interspecies transmission of viral pathogens. Nat Med 2004; 10 (12, Suppl): S77-S81
    CrossrefPubMedGoogle Scholar
  • 36 Lim JK, Murphy PM. Chemokine control of West Nile virus infection. Exp Cell Res 2011; 317 (5) 569-574
    CrossrefPubMedGoogle Scholar
  • 37 Sahlberg AS, Granfors K, Penttinen MA. HLA-B27 and host-pathogen interaction. Adv Exp Med Biol 2009; 649: 235-244
    PubMedGoogle Scholar
  • 38 Kaur P, Basu S. Transfusion-transmitted infections: existing and emerging pathogens. J Postgrad Med 2005; 51 (2) 146-151
    PubMedGoogle Scholar
  • 39 Wolfe ND, Dunavan CP, Diamond J. Origins of major human infectious diseases. Nature 2007; 447 (7142) 279-283
    CrossrefPubMedGoogle Scholar
  • 40 Zappa A, Amendola A, Romanò L, Zanetti A. Emerging and re-emerging viruses in the era of globalisation. Blood Transfus 2009; 7 (3) 167-171
    PubMedGoogle Scholar
  • 41 Woolhouse ME, Haydon DT, Antia R. Emerging pathogens: the epidemiology and evolution of species jumps. Trends Ecol Evol 2005; 20 (5) 238-244
    CrossrefPubMedGoogle Scholar
  • 42 Chamberland ME. Emerging infectious agents: do they pose a risk to the safety of transfused blood and blood products?. Clin Infect Dis 2002; 34 (6) 797-805
    CrossrefPubMedGoogle Scholar
  • 43 Grillberger L, Kreil TR, Nasr S, Reiter M. Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells. Biotechnol J 2009; 4 (2) 186-201
    CrossrefPubMedGoogle Scholar
  • 44 Dodd RY, Leiby DA. Emerging infectious threats to the blood supply. Annu Rev Med 2004; 55: 191-207
    CrossrefPubMedGoogle Scholar
  • 45 Stramer SL, Hollinger FB, Katz LM , et al. Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion 2009; 49 (Suppl. 02) 1S-29S
    CrossrefPubMedGoogle Scholar
  • 46 Smolinski S, Hamburg MA, Lederberg J. Microbial threats to health: emergence, detection, and response. Washington, DC: National Academies Press; 2003
    Google Scholar
  • 47 Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev 2012; 7: CD002063
    PubMedGoogle Scholar
  • 48 Ludlam CA, Powderly WG, Bozzette S , et al. Clinical perspectives of emerging pathogens in bleeding disorders. Lancet 2006; 367 (9506) 252-261
    CrossrefPubMedGoogle Scholar
  • 49 Grazzini G, Liumbruno GM, Pupella S , et al. West Nile virus in Italy: a further threat to blood safety, a further challenge to the blood system. Blood Transfus 2008; 6 (4) 235-237
    PubMedGoogle Scholar
  • 50 Ludlam CA, Turner ML. Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products. Br J Haematol 2006; 132 (1) 13-24
    CrossrefPubMedGoogle Scholar
  • 51 Liumbruno GM, Calteri D, Petropulacos K , et al. The Chikungunya epidemic in Italy and its repercussion on the blood system. Blood Transfus 2008; 6 (4) 199-210
    PubMedGoogle Scholar
  • 52 Sheldon J, Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother 2008; 61 (4) 766-768
    CrossrefPubMedGoogle Scholar
  • 53 Stramer SL, Zou S, Notari EP , et al. Blood donation screening for hepatitis B virus markers in the era of nucleic acid testing: are all tests of value?. Transfusion 2012; 52 (2) 440-446
    CrossrefPubMedGoogle Scholar
  • 54 Sharp CP, Lail A, Donfield S, Gomperts ED, Simmonds P. Virologic and clinical features of primary infection with human parvovirus 4 in subjects with hemophilia: frequent transmission by virally inactivated clotting factor concentrates. Transfusion 2012; 52 (7) 1482-1489
    CrossrefPubMedGoogle Scholar
  • 55 Soucie JM, De Staercke C, Monahan PE , et al; the US Hemophilia Treatment Center Network. Evidence for the transmission of parvovirus B19 in patients with bleeding disorders treated with plasma-derived factor concentrates in the era of nucleic acid test screening. Transfusion 2013; 53 (6) 1217-1225
    CrossrefPubMedGoogle Scholar
  • 56 Brown P. Creutzfeldt-Jakob disease: reflections on the risk from blood product therapy. Haemophilia 2007; 13 (Suppl. 05) 33-40
    CrossrefPubMedGoogle Scholar
  • 57 Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiolgoical Review Study. Vox Sang 2006; 91 (3) 221-230
    CrossrefPubMedGoogle Scholar
  • 58 Wroe SJ, Pal S, Siddique D , et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006; 368 (9552) 2061-2067
    CrossrefPubMedGoogle Scholar
  • 59 Peden A, McCardle L, Head MW , et al. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 2010; 16 (2) 296-304
    CrossrefPubMedGoogle Scholar
  • 60 Allain JP, Stramer SL, Carneiro-Proietti AB , et al. Transfusion-transmitted infectious diseases. Biologicals 2009; 37 (2) 71-77
    CrossrefPubMedGoogle Scholar
  • 61 Stein J, Besley J, Brook C , et al. Risk-based decision-making for blood safety: preliminary report of a consensus conference. Vox Sang 2011; 101 (4) 277-281
    CrossrefPubMedGoogle Scholar
  • 62 Bolton-Maggs PH. Optimal haemophilia care versus the reality. Br J Haematol 2006; 132 (6) 671-682
    CrossrefPubMedGoogle Scholar
  • 63 Evatt BL, Austin H, Leon G, Ruiz-Sáez A, De Bosch N. Haemophilia therapy: assessing the cumulative risk of HIV exposure by cryoprecipitate. Haemophilia 1999; 5 (5) 295-300
    CrossrefPubMedGoogle Scholar
  • 64 Spannagl M, Joch Ch, Heindl B. [Safety of plasma-derived factor concentrates: an example of pharmacovigilance with fibrinogen and factor XIII-concentrate]. Hamostaseologie 2006; 26 (3) (Suppl. 01) S36-S40
    PubMedGoogle Scholar
  • 65 Lusher JM, Scharrer I. Evolution of recombinant factor VIII safety: KOGENATE and Kogenate FS/Bayer. Int J Hematol 2009; 90 (4) 446-454
    CrossrefPubMedGoogle Scholar
  • 66 Mackay GA, Knight RS, Ironside JW. The molecular epidemiology of variant CJD. Int J Mol Epidemiol Genet 2011; 2 (3) 217-227
    PubMedGoogle Scholar
  • 67 Bishop MT, Pennington C, Heath CA, Will RG, Knight RS. PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism. BMC Med Genet 2009; 10: 146
    CrossrefPubMedGoogle Scholar
  • 68 Mead S, Poulter M, Uphill J , et al. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol 2009; 8 (1) 57-66
    CrossrefPubMedGoogle Scholar
  • 69 Bishop MT, Kovacs GG, Sanchez-Juan P, Knight RS. Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease. BMC Med Genet 2008; 9: 31
    CrossrefPubMedGoogle Scholar
  • 70 Franchini M, Tagliaferri A, Mannucci PM. The management of hemophilia in elderly patients. Clin Interv Aging 2007; 2 (3) 361-368
    PubMedGoogle Scholar
  • 71 Mannucci PM, Schutgens RE, Santagostino E, Mauser-Bunschoten EP. How I treat age-related morbidities in elderly persons with hemophilia. Blood 2009; 114 (26) 5256-5263
    CrossrefPubMedGoogle Scholar
  • 72 Knight R, Stanley S, Wong M, Dolan G. Hemophilia therapy and blood-borne pathogen risk. Semin Thromb Hemost 2006; 32 (Suppl. 02) 3-9
    PubMedGoogle Scholar
  • 73 Tapper ML. Emerging viral diseases and infectious disease risks. Haemophilia 2006; 12 (Suppl. 01) 3-7 , discussion 26–28
    PubMedGoogle Scholar
  • 74 Grard G, Fair JN, Lee D , et al. A novel rhabdovirus associated with acute hemorrhagic fever in central Africa. PLoS Pathog 2012; 8 (9) e1002924
    CrossrefPubMedGoogle Scholar
  • 75 Health Protection Agency. Summary results of the second national survey of abnormal prion protein prevalence in archived appendix specimens. Health Protection Report 2012. http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlprn. Published August 2012. Accessed 5 June 2013.
    PubMedGoogle Scholar
  • 76 Katz LM. Transfusion safety in the 21st century: how tightly should the blood community close the window(s)?. J Infect Dis 2008; 198 (9) 1258-1261
    CrossrefPubMedGoogle Scholar