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Effects of factor VIII concentrates on the immune system in hemophilic patients

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  1. 0.

    Agostini C, Semenzato G, Vinante F, Sinicco A, Trentin L, Zambello R, Zuppini B, Zanotti R, Siviero F, Veneri D, Foà R, Pizzolo G (1989) Increased levels of soluble CD 8 molecule in the serum of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related disorders. Clin Immunol Immunopathol 50: 146–153

  2. 1.

    Antonaci S, Jirillo E, Stasi D, De Mitrio V, La Via MF, Bonomo L (1987) Immunoresponsiveness in haemophilia: lymphocyte and phagocyte mediated functions. Diagn Clin Immunol 5: 318–325

  3. 2.

    Berntorp E (1988) Lectin-induced lymphocyte transformation after infusion of factor VIII concentrates. In: Mannucci PM (ed) Replacement therapy in haemophilia — problems and solutions. Alden Press, Lisbon, pp 129

  4. 3.

    Boese EC, Tantum KR, Eyster ME (1979) Pulmonary function abnormalities after infusion of antihemophilic factor (AHF) concentrates. Am J Med 67: 474–476

  5. 4.

    Brettler DB, Forsberg AD, Brewster F, Sullivan JL, Levine PH (1986) Delayed cutaneous hypersensitivity reactions in hemophilic subjects treated with factor concentrate. Am J Med 81: 607–611

  6. 4a.

    Brettler DB, Forsberg AD, Levine PH, Petillo J, Lamon K, Sullivan JL (1989) Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies. Blood 73: 1859–1863

  7. 5.

    Brieva JA, Sequi J, Zabay JM, Pardo A, Compos A, De La Sen ML, Bootello A (1985) Abnormal B cell function in haemophiliacs and their relationship with factor concentrate administration. Clin Exp Immunol 59: 491–498

  8. 6.

    Carr R, Veitch SE, Edmond E, Peutherer JF, Prescott RJ, Steel CM, Ludlam CA (1984) Abnormalities of circulating lymphocyte subsets in haemophiliacs in an AIDS-free population. Lancet I: 1431–1434

  9. 7.

    Eibl MM, Ahmad R, Wolf HM, Linnau Y, Götz E, Mannhalter JW (1987) A component of factor VIII preparations which can be separated from factor VIII activity down-modulates human monocyte functions. Blood 69: 1153–1160

  10. 8.

    Eyster ME, Nan ME (1978) Particulate material in antihemophilic factor (AHF) concentrates. Transfusion 18: 576–581

  11. 9.

    Freedman I, Mazaheri R, Read S, Garvey MB, Teitel J (1987) Humoral and cellular immune abnormalities in adult hemophiliacs followed over a two-year period. Diagn Clin Immunol 5: 30–40

  12. 10.

    Froebel KS, Madhok R, Forbes CD, Lennie SE, Lowe GDO, Sturrock RD (1983) Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate? Br Med J 287: 1091–1093

  13. 11.

    Gamba G, Ippoliti G, Bajani G, Ricevuti G, Mazzone A, Badarida G, Gobbi P, Geroldi D, Ascari E (1987) Immunologic status, granulocyte chemotaxis and antibodies to HTLV III/ LAV in haemophiliacs treated with clotting factor concentrates. Haematologica 72: 129–135

  14. 12.

    Glöckel U, Gromball J, Kobatsch B, Leppik KH, Leibold W, Beck JD (1987) Influence of factor VIII, factor IX and immunoglobulin preparations on proliferative responses of mitogen-activated lymphocytes. Immun Infect 15: 62–65

  15. 13.

    Gody M, Smidt I, Onattara SA, De-Thé G (1988) HIV-1 and HIV-2 related AIDS as observed in Abidjan area, Ivory Coast (abstract 5016). Proceedings, 14th International Conference on AIDS, Stockholm, June 13–17, p 318

  16. 14.

    Goldsmith GH, Baily RG, Brettler DB, Davidson WR, Ballard JO, Driscol TE, Greenberg JM, Kasper CK, Levine PH, Ratnoff OD (1988) Primary pulmonary hypertension in patients with classic hemophilia. Ann Intern Med 108: 797–799

  17. 14a.

    Gomperts E, Addiego J, Gill J, Levine P, Kessler C, Schulman S, Lewis B, Brackmann H, Sharrer I, Courter S, Lee M (1989) Immunological function in hemophiliacs treated with plasma derived mAb purified F VIII concentrate (abstr 545). Thromb Hemostas 62: 181

  18. 14b.

    Green D, Deutsche J, Goldsmith JM (1989) CD 4 cell concentrations in HIV-positive hemophiliacs treated with high or intermediate-purity clotting factor concentrates (abstr 371). Blood 74 [Suppl 1]: 99a

  19. 15.

    Hay CRM, McEvoy P (1989) The variable effect of diverse clotting factor concentrates on lymphocyte function in vitro (abstract 1461). Thromb Haemost 62: 453

  20. 16.

    Hollán SR, Füst G, Nagy K, Horváth A, Králl G, Verebélyi K, Ujhelyi E, Varga L, Mayer V (1985) Immunological alteration in anti-HTLV-III negative haemophiliacs and homosexual men in Hungary. Immunol Lett 11: 305–310

  21. 17.

    Horvat RT, Wood C, Balachandran N (1989) Transactivation of human immunodeficiency virus promoter by human herpesvirus 6. J Virol 63: 970–973

  22. 18.

    Ingerslev J (1988) Assessment of murine immunoglobulins in monoclonal antibody-purified factor VIII concentrates. In: Mannucci PM (ed) Replacement therapy in haemophilia — problems and solutions. Alden Press, Lisbon, pp 131–133

  23. 19.

    Janco L, Puryear PJ (1989) Commercial factor VIII concentrates alter human monocyte functions in vitro (abstract 898). Pediatr Res 25

  24. 19a.

    Lederman MM, Saunders C, Toossi Z, Lemon N, Everson B, Ratnoff OD (1986) Antihemophilic factor (factor VIII) preparations inhibit lymphocyte proliferation and production of interleukin-2. J Lab Clin Med 107: 471–478

  25. 20.

    Ludlam CA (1988) Effects of allogens in blood products on immunity. Semin Hematol 25 [Suppl 1]: 3–7

  26. 21.

    Ludlam CA, Steel CM, Cheingsong-Popov R, McClelland DBL, Tucker J, Tedder RS, Weiss RA, Philip I, Prescott RJ (1985) Human T-lymphotropic virus type III (HTLV III) infection in seronegative haemophiliacs after transfusion of factor VIII. Lancet II: 233–236

  27. 22.

    Ludlam CA, Carr R, Veitch E, Steel CM (1983) Disordered immune regulation in haemophiliacs not exposed to commercial factor VIII. Lancet I: 1226

  28. 23.

    Madhok R (1988) The in-vivo and in-vitro effects of clotting factor concentrates on the immune system. In: Mannucci PM (ed) Replacement therapy in haemophilia — problems and solutions. Alden Press, Lisbon, pp 56–59

  29. 24.

    Madhok R, Gracie A, Lowe GDO, Burnett A, Froebel K, Follett E, Forbes CD (1986) Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus. Br Med J 293: 978–980

  30. 25.

    Mahir WS, Millard RE, Booth JC, Flute PT (1988) Functional studies of cell-mediated immunity in haemophilia and other bleeding disorders. Br J Haematol 69: 367–370

  31. 26.

    Mannhalter JW, Zlabinger GJ, Ahmad R, Lebl H, Zielinski CC, Schramm W, Eibl MM (1986) A functional defect in the early phase of the immune response observed in patients with hemophilia A. Clin Immunol Immunopathol 38: 390–397

  32. 27.

    Mannhalter JW, Ahmad R, Lebl H, Göttlicher J, Wolf HM, Eibl MM (1988) Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity. Blood 71: 1662–1668

  33. 28.

    Mannhalter JW, Ahmad R, Eibl MM, Leibl H (1990) Modulation of human monocyte functions by factor VIII-anti-factor VIII complexes present in an affinity-purified factor VIII product. Blood 75: 810–811

  34. 29.

    Matheson DS, Green BJ, Poon M-C, Fritzler MJ, Hoar DI, Bowen TJ (1986) Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon. Blood 67: 164–167

  35. 30.

    Mogensen O, Mogensen B, Jakobsen A, Sell A (1986) Tumor markers in ovarian cancer: a comparison between immunosuppressive acidic protein and alpha1 acid glycoprotein. Am J Obstet Gynecol 154: 1165–1166

  36. 31.

    Murray HW, Rubin BY, Masur H, Roberts RB (1984) Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 310: 883–889

  37. 32.

    Nabel GJ (1988) Activation of human immunodeficiency virus. J Lab Clin Med 111: 495–500

  38. 33.

    Pasi KJ, Hill FGH (1988) Correlation between increasing product purity and reduced inhibition of monocyte phagocytic function. In: Mannucci PM (ed) Replacement therapy in haemophilia — problems and solutions. Alden Press, Lisbon, pp 116–119

  39. 34.

    Quinn TC, Piot P, McCormick JB, Feinsod FM, Taelman H, Kapita B, Stevens W, Fauci AS (1987) Serologic and immunologic studies in patients with AIDS in North America and Africa. JAMA 257: 2617–2621

  40. 35.

    Ragni MV, Winkelstein A, Kingsley L, Spero JA, Lewis JH (1987) 1986 update of HIV seroprevalence, AIDS incidence and immunologic correlates of HIV infection in patients with hemophilia A and B. Blood 70: 786–790

  41. 36.

    Roy G, Pardo A, Leyva-Cobián F (1988) Phenotypic and functional abnormalities in monocytes from patients with haemophilia A treated with factor VIII concentrates. Acta Haematol 79: 26–32

  42. 37.

    Ruffault R, Genetet N, Berthier AM, Pommereuil M, Duvail C, Andre P, Morel H, Genetet B, Fauconnier B (1988) Interferon production in severe hemophiliacs with and without HIV antibodies. J Interferon Res 8: 89–94

  43. 38.

    Schreiber A (1988) The preclinical characterization of Monoclate factor VIII:c, antihaemophilic factor (human). Semin Haematol 25 [Suppl 1]: 27–32

  44. 39.

    Schreiber AB, Gillette R, Hrinda MR (1987) In vitro immune parameters of Monoclate, a monoclonal antibody purified human plasma factor VIII:c therapeutic preparation (abstract 1252). Thromb Haemost 58: 346

  45. 40.

    Schulman S, Johnsson H (1989) Beneficial effect of an ultrapure factor VIII concentrate on hypergammaglobulinemia in HIV-positive hemophiliacs (abstract Th B P 6). Proceedings, 5th International Conference on AIDS, Montreal, June 4–9, p 416

  46. 41.

    Schulman S, Johnsson H, Blomqvist S (1988) Pulmonary hypertension in hemophilia (letter). Ann Intern Med 109: 759–760

  47. 42.

    Shulman G, Ballard JO, Eyster ME (1985) Changes in plasma haptoglobin and alpha-2-macroglobulin in hemophiliacs receiving factor replacement therapy. Am J Hematol 18: 223–233

  48. 43.

    Stein SF, Evatt BL, McDougal JS, Lawrence DN, Holman RC, Ramsey RB, Spira TJ (1985) A longitudinal study of patients with hemophilia: immunologic correlates of infection with HTLV III/LAV and other viruses. Blood 66: 973–979

  49. 44.

    Tamura K, Shibata Y, Matsuda Y, Shimizu Y (1981) Isolation and characterization of an immunosuppressive acidic protein from ascitic fluids of cancer patients. Cancer Res 41: 3244–3252

  50. 45.

    Thorpe R, Dilger P, Dawson NJ, Barrowcliffe TW (1989) Inhibition of interleukin-2 secretion by factor VIII concentrates: a possible cause of immunosuppression in haemophiliacs. Br J Haematol 71: 387–391

  51. 45a.

    Walsh C, Krigel R, Lennette E, Karpatkin S (1985) Thrombocytopenia in homosexual patients. Ann Intern Med 103: 542–545

  52. 46.

    Webster A, Lee CA, Cook DG, Grundy JE, Emery VC, Kernoff PBA, Griffiths PD (1989) Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection. Lancet II: 63–66

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Schulman, S. Effects of factor VIII concentrates on the immune system in hemophilic patients. Ann Hematol 63, 145–151 (1991).

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  • Public Health
  • Immune System
  • Factor Viii
  • Hemophilic Patient