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Semin Thromb Hemost 2016; 42(05): 583-588
DOI: 10.1055/s-0036-1571314
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Safety Issues of Plasma-Derived Products for Treatment of Inherited Bleeding Disorders

Albert Farrugia
1   School of Surgery, QEII Medical Centre, The University of Western Australia, Western Australia, Australia
2   Kedrion S.p.A, Via del Ciocco, Castelvecchio Pascoli, Lucca, Italy
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Publication History

Publication Date:
14 April 2016 (online)

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Abstract

The infection by blood-borne pathogens of a large proportion of the treated hemophilia population over the 1970s to 1990s represents a major tragedy that is embedded in the history of this condition. To avoid this historical repetition, the community of patients, treaters, and policy makers that contribute to hemophilia care need to learn from the events that gave rise to it. This requires an appreciation of the measures, which, through scientific developments, have enhanced greatly the safety of plasma-derived coagulation factor concentrates (pd CFCs). The objective conditions underlying and influencing the safety of all biological materials also require recognition. Although the stringent measures which ensure the safety of pd CFCs are very effective, pathogen transmission by other blood-derived therapeutics has continued due to a lack of effective technology and the continued emergence of new agents which transmit disease. This emphasizes the reality that the basic environmental factors influencing blood pathogen safety have not changed, albeit our capacity to counter them has improved greatly. These factors lead to threats to blood safety that are unpredictable and imposable on a global scale. The likelihood of a continued role for pd CFCs in hemophilia care, particularly in emerging countries challenged to maintain blood safety measures, ensures that these issues are more current than historical.

Keywords

blood safety - viruses - plasma products
 

  • References

  • 1 Farrugia A, Castaman G. Inhibitors and product choice in haemophilia – clinical opinion in Italian treaters through an elicitation. Blood Transfus 2015; 18: s527-s559
    PubMedGoogle Scholar
  • 2 Leveton LB, Sox Jr HC, Stoto MA. HIV and the Blood Supply: An Analysis of Crisis Decisionmaking (Internet). 1995 Available at: http://www.nap.edu/catalog/4989/hiv-and-the-blood-supply-an-analysis-of-crisis-decisionmaking . Accessed August 25, 2015
    PubMedGoogle Scholar
  • 3 Evatt BL. The tragic history of AIDS in the hemophilia population, 1982-1984. J Thromb Haemost 2006; 4 (11) 2295-2301
    CrossrefPubMedGoogle Scholar
  • 4 Wilson K. The Krever Commission—10 years later. CMAJ 2007; 177 (11) 1387-1389
    CrossrefPubMedGoogle Scholar
  • 5 Wilson K. A framework for applying the precautionary principle to transfusion safety. Transfus Med Rev 2011; 25 (3) 177-183
    CrossrefPubMedGoogle Scholar
  • 6 Soucie JM, Richardson LC, Evatt BL , et al; Hemophilia Surveillance System Project Investigators. Risk factors for infection with HBV and HCV in a largecohort of hemophiliac males. Transfusion 2001; 41 (3) 338-343
    CrossrefPubMedGoogle Scholar
  • 7 Klamroth R, Gröner A, Simon TL. Pathogen inactivation and removal methods for plasma-derived clotting factor concentrates. Transfusion 2014; 54 (5) 1406-1417
    CrossrefPubMedGoogle Scholar
  • 8 Kreil TR. New Technologies for Virus Detection: Where Donor Screening is Going. WFH Global Forum: Montreal, QC (Internet); September 26–27, 2013. Available at: http://www1.wfh.org/docs/en/Events/GF2013/GF2013_Kreil.pdf . Accessed August 31, 2015
    PubMedGoogle Scholar
  • 9 van den Berg W, ten Cate JW, Breederveld C, Goudsmit J. Seroconversion to HTLV-III haemophiliac given heat-treated factor VIII concentrate. Lancet 1986; 1 (8484) 803-804
    PubMedGoogle Scholar
  • 10 White II GC, Matthews TJ, Weinhold KJ , et al. HTLV-III seroconversion associated with heat-treated factor VIII concentrate. Lancet 1986; 1 (8481) 611-612
    PubMedGoogle Scholar
  • 11 Weisser J. Transmission of the human immunodeficiency virus by a dry heat-treated Factor VIII concentrate? [in German]. Klin Padiatr 1988; 200 (5) 375-379
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Isarangkura P, Mahaphan W, Chiewsilp P, Chuansumrit A, Hathirat P. HIV transmission by seronegative blood components: report of 2 probable cases. Vox Sang 1993; 65 (2) 114-116
    CrossrefPubMedGoogle Scholar
  • 13 Evensen SA, Ulstrup J, Skaug K, Frøland SS, Glomstein A, Rollag H. HIV infection in Norwegian haemophiliacs: the prevalence of antibodies against HIV in haemophiliacs treated with lyophilized cryoprecipitate from volunteer donors. Eur J Haematol 1987; 39 (1) 44-48
    PubMedGoogle Scholar
  • 14 Centers for Disease Control and Prevention (CDC). Fatal West Nile virus infection after probable transfusion-associated transmission—Colorado, 2012. MMWR Morb Mortal Wkly Rep 2013; 62 (31) 622-624
    PubMedGoogle Scholar
  • 15 Oh HB, Muthu V, Daruwalla ZJ, Lee SY, Koay ES, Tambyah PA. Bitten by a bug or a bag? Transfusion-transmitted dengue: a rare complication in the bleeding surgical patient. Transfusion 2015; 55 (7) 1655-1661
    CrossrefPubMedGoogle Scholar
  • 16 Kreil TR, Berting A, Kistner O, Kindermann J. West Nile virus and the safety of plasma derivatives: verification of high safety margins, and the validity of predictions based on model virus data. Transfusion 2003; 43 (8) 1023-1028
    CrossrefPubMedGoogle Scholar
  • 17 Centers for Disease Control and Prevention (CDC). HIV transmission through transfusion --- Missouri and Colorado, 2008. MMWR Morb Mortal Wkly Rep 2010; 59 (41) 1335-1339
    PubMedGoogle Scholar
  • 18 Spreafico M, Berzuini A, Foglieni B , et al. Poor efficacy of nucleic acid testing in identifying occult HBV infection and consequences for safety of blood supply in Italy. J Hepatol 2015; 63 (5) 1068-1076
    CrossrefPubMedGoogle Scholar
  • 19 Pustoslemsek P, Kloft M, Kotitschke R. Biotest position on HIV-1 seroconversions in 1990 in 11 patients, treated with beta-propiolactone/uv virus inactivated PPSB [in German]. Infusionsther Transfusionsmed 1993; 20 (6) 344-346
    PubMedGoogle Scholar
  • 20 Scheidler A, Rokos K, Reuter T, Ebermann R, Pauli G. Inactivation of viruses by beta-propiolactone in human cryo poor plasma and IgG concentrates. Biologicals 1998; 26 (2) 135-144
    CrossrefPubMedGoogle Scholar
  • 21 Farrugia A. Globalisation and blood safety. Blood Rev 2009; 23 (3) 123-128
    CrossrefPubMedGoogle Scholar
  • 22 Murphy WG. Disease transmission by blood products: past, present and future. Pathophysiol Haemost Thromb 2002; 32 (Suppl. 01) 1-4
    PubMedGoogle Scholar
  • 23 Rosendaal FR, Nieuwenhuis HK, van den Berg HM , et al; Dutch Hemophilia Study Group. A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Blood 1993; 81 (8) 2180-2186
    PubMedGoogle Scholar
  • 24 Prowse C, Follett E, Prince A , eds. Hepatitis A Virus Transmission by Blood Products. Symposium, New York, July 1993: Proceedings. S. Karger AG; 1994
    PubMedGoogle Scholar
  • 25 Yu MW. Follow-up studies of hepatitis C association with an intravenous immunoglobulin. Dev Biol Stand 1996; 88: 215-216
    PubMedGoogle Scholar
  • 26 Romberg V, Hoefferer L, El Menyawi I. Effects of the manufacturing process on the anti-A isoagglutinin titers in intravenous immunoglobulin products. Transfusion 2015; 55 (Suppl. 02) S105-S109
    CrossrefPubMedGoogle Scholar
  • 27 Lynch TJ, Weinstein MJ, Tankersley DL, Fratantoni JC, Finlayson JS. Considerations of pool size in the manufacture of plasma derivatives. Transfusion 1996; 36 (9) 770-775
    PubMedGoogle Scholar
  • 28 Evatt B, Austin H, Leon G, Ruiz-Sáez A, de Bosch N. Hemophilia treatment. Predicting the long-term risk of HIV exposure by cryoprecipitate. Haemophilia 2000; 6 (Suppl. 01) 128-132
    CrossrefPubMedGoogle Scholar
  • 29 Yee TT, Lee CA, Pasi KJ. Life-threatening human parvovirus B19 infection in immunocompetent haemophilia. Lancet 1995; 345 (8952) 794-795
    PubMedGoogle Scholar
  • 30 Soucie JM, Siwak EB, Hooper WC, Evatt BL, Hollinger FB ; Universal Data Collection Project Working Group. Human parvovirus B19 in young male patients with hemophilia A: associations with treatment product exposure and joint range-of-motion limitation. Transfusion 2004; 44 (8) 1179-1185
    CrossrefPubMedGoogle Scholar
  • 31 Geng Y, Wu C-G, Bhattacharyya SP, Tan D, Guo Z-P, Yu MY. Parvovirus B19 DNA in Factor VIII concentrates: effects of manufacturing procedures and B19 screening by nucleic acid testing. Transfusion 2007; 47 (5) 883-889
    CrossrefPubMedGoogle Scholar
  • 32 Soucie JM, De Staercke C, Monahan PE , et al; 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
  • 33 Blümel J, Schmidt I, Effenberger W , et al. Parvovirus B19 transmission by heat-treated clotting factor concentrates. Transfusion 2002; 42 (11) 1473-1481
    CrossrefPubMedGoogle Scholar
  • 34 Berting A, Modrof J, Unger U , et al. Inactivation of parvovirus B19 during STIM-4 vapor heat treatment of three coagulation factor concentrates. Transfusion 2008; 48 (6) 1220-1226
    CrossrefPubMedGoogle Scholar
  • 35 Kreil TR, Wieser A, Berting A , et al. Removal of small nonenveloped viruses by antibody-enhanced nanofiltration during the manufacture of plasma derivatives. Transfusion 2006; 46 (7) 1143-1151
    CrossrefPubMedGoogle Scholar
  • 36 Chtourou S, Porte P, Nogré M , et al. A solvent/detergent-treated and 15-nm filtered factor VIII: a new safety standard for plasma-derived coagulation factor concentrates. Vox Sang 2007; 92 (4) 327-337
    PubMedGoogle Scholar
  • 37 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
  • 38 Baylis SA, Tuke PW, Miyagawa E, Blümel J. Studies on the inactivation of human parvovirus 4. Transfusion 2013; 53 (10 Pt 2): 2585-2592
    CrossrefPubMedGoogle Scholar
  • 39 Barzilai A, Schulman S, Karetnyi YV , et al. Hepatitis E virus infection in hemophiliacs. J Med Virol 1995; 46 (2) 153-156
    CrossrefPubMedGoogle Scholar
  • 40 Ben-Ayed Y, Hannachi H, Ben-Alaya-Bouafif N, Gouider E, Triki H, Bahri O. Hepatitis E virus seroprevalence among hemodialysis and hemophiliac patients in Tunisia (North Africa). J Med Virol 2015; 87 (3) 441-445
    CrossrefPubMedGoogle Scholar
  • 41 Toyoda H, Honda T, Hayashi K , et al. Prevalence of hepatitis E virus IgG antibody in Japanese patients with hemophilia. Intervirology 2008; 51 (1) 21-25
    CrossrefPubMedGoogle Scholar
  • 42 Juhl D, Baylis SA, Blümel J, Görg S, Hennig H. Seroprevalence and incidence of hepatitis E virus infection in German blood donors. Transfusion 2014; 54 (1) 49-56
    CrossrefPubMedGoogle Scholar
  • 43 Delwart E. Human parvovirus 4 in the blood supply and transmission by pooled plasma-derived clotting factors: does it matter?. Transfusion 2012; 52 (7) 1398-1403
    CrossrefPubMedGoogle Scholar
  • 44 Cai K, Gröner A, Dichtelmüller HO , et al. Prion removal capacity of plasma protein manufacturing processes: a data collection from PPTA member companies. Transfusion 2013; 53 (9) 1894-1905
    CrossrefPubMedGoogle Scholar
  • 45 Brown P, Rohwer RG, Dunstan BC, MacAuley C, Gajdusek DC, Drohan WN. The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 1998; 38 (9) 810-816
    CrossrefPubMedGoogle Scholar
  • 46 Gregori L, Maring J-A, MacAuley C , et al. Partitioning of TSE infectivity during ethanol fractionation of human plasma. Biologicals 2004; 32 (1) 1-10
    CrossrefPubMedGoogle Scholar
  • 47 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
  • 48 Roberts PL, Dalton J, Evans D , et al. Removal of TSE agent from plasma products manufactured in the United Kingdom. Vox Sang 2013; 104 (4) 299-308
    CrossrefPubMedGoogle Scholar
  • 49 El-Shanawany T, Jolles S, Unsworth DJ, Williams P. A recipient of immunoglobulin from a donor who developed vCJD. Vox Sang 2009; 96 (3) 270-270
    CrossrefPubMedGoogle Scholar
  • 50 Groener A, Groschup M, Schäfer W. Paper: Efficient Reduction of Prions by the Manufacturing Process of a VWF/FVIII Product (Internet). 2008 (cited September 2, 2015). Available at: https://ash.confex.com/ash/2008/webprogram/Paper3934.html
    PubMedGoogle Scholar
  • 51 Zou S, Fang CT, Schonberger LB. Transfusion transmission of human prion diseases. Transfus Med Rev 2008; 22 (1) 58-69
    CrossrefPubMedGoogle Scholar
  • 52 Jackson GS, Burk-Rafel J, Edgeworth JA , et al. A highly specific blood test for vCJD. Blood 2014; 123 (3) 452-453
    CrossrefPubMedGoogle Scholar
  • 53 Stonebraker JS, Brooker M, Amand RE, Farrugia A, Srivastava A. A study of reported factor VIII use around the world. Haemophilia 2010; 16 (1) 33-46
    CrossrefPubMedGoogle Scholar
  • 54 Ghosh K, Joshi SH, Shetty S , et al. Transfusion transmitted diseases in haemophilics from western India. Indian J Med Res 2000; 112: 61-64
    PubMedGoogle Scholar
  • 55 Dubey A, Verma A, Elhence P, Agarwal P. Evaluation of transfusion-related complications along with estimation of inhibitors in patients with hemophilia: A pilot study from a single center. Asian J Transfus Sci 2013; 7 (1) 8-10
    CrossrefPubMedGoogle Scholar
  • 56 Timan IS, Aulia D, Atmakusma D, Sudoyo A, Windiastuti E, Kosasih A. Some hematological problems in Indonesia. Int J Hematol 2002; 76 (Suppl. 01) 286-290
    CrossrefPubMedGoogle Scholar
  • 57 Burnouf T, Radosevich M, El-Ekiaby M, Goubran H. Pathogen reduction technique for fresh-frozen plasma, cryoprecipitate, and plasma fraction minipools prepared in disposable processing bag systems. Transfusion 2011; 51 (2) 446-447 , author reply 447–448
    CrossrefPubMedGoogle Scholar
  • 58 The Right Honuorable Lord Penrose. Penrose Inquiry (Internet). 2015 (cited August 25, 2015). Available at: http://www.penroseinquiry.org.uk/
    PubMedGoogle Scholar