Skip to main content
NCBI home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 1985 Jun;60(6):530–536. doi: 10.1136/adc.60.6.530

Lymphocyte subset ratios and factor VIII usage in haemophilia.

A C Beddall, K Al-Rubei, M D Williams, F G Hill
PMCID: PMC1777360  PMID: 3925894

Abstract

Type and quantity of replacement treatment, together with haematological and immunological parameters were determined in 37 boys with severe haemophilia A and 41 children with other bleeding disorders. The quantity of factor VIII concentrate given to boys with severe haemophilia A (mean U/year) showed a significant inverse correlation with total white cell counts, lymphocyte counts, platelet counts, and the ratio of monoclonal antibody defined T lymphocyte subsets, T4 and T8 (T4:T8). Of the boys with severe haemophilia A, 49% had inversed T4:T8 ratios and 24% had thrombocytopenia. Treatment with high dose factor VIII concentrate (more than 25 000 U/year) was associated with low platelet counts, low lymphocyte counts, low T4:T8 ratios, and hypergammaglobulinaemia. In addition, six patients with severe haemophilia A and factor VIII inhibitors had inversed T4:T8 ratios. Patients treated exclusively with cryoprecipitate or prothrombin complex concentrates had normal T4:T8 ratios and platelet counts. The severity of the haematological and immunological abnormalities observed seems to be associated with high usage of factor VIII concentrates. Similar abnormalities have been described in patients with the acquired immune deficiency syndrome (AIDS). Prospective study of haemophiliacs is required to assess long term sequelae of factor concentrate usage, including the possible development of AIDS.

Full text

PDF
530

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bloom A. L. Acquired immunodeficiency syndrome and other possible immunological disorders in European haemophiliacs. Lancet. 1984 Jun 30;1(8392):1452–1455. doi: 10.1016/s0140-6736(84)91942-1. [DOI] [PubMed] [Google Scholar]
  2. Boigne J. M., Boigne N., Galacteros F., Nalpas B., Philippon C., Vivien C. Dosage des protéines par immunoprécipitation sur analyseur centrifuge Centrifichem. Ann Biol Clin (Paris) 1977;35(3):237–254. [PubMed] [Google Scholar]
  3. Carney W. P., Rubin R. H., Hoffman R. A., Hansen W. P., Healey K., Hirsch M. S. Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis. J Immunol. 1981 Jun;126(6):2114–2116. [PubMed] [Google Scholar]
  4. Carr R., Veitch S. E., Edmond E., Peutherer J. F., Prescott R. J., Steel C. M., Ludlam C. A. Abnormalities of circulating lymphocyte subsets in haemophiliacs in an AIDS-free population. Lancet. 1984 Jun 30;1(8392):1431–1434. doi: 10.1016/s0140-6736(84)91931-7. [DOI] [PubMed] [Google Scholar]
  5. Craske J., Kirk P., Cohen B., Vandervelde E. M. Commercial factor VIII associated hepatitis, 1974-75, in the United Kingdom: a retrospective survey. J Hyg (Lond) 1978 Jun;80(3):327–336. doi: 10.1017/s0022172400024773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daly H. M., Scott G. L. Fatal AIDS in a UK haemophiliac. Lancet. 1984 Jan 7;1(8367):44–44. doi: 10.1016/s0140-6736(84)90203-4. [DOI] [PubMed] [Google Scholar]
  7. De Waele M., Thielemans C., Van Camp B. K. Characterization of immunoregulatory T cells in EBV-induced infectious mononucleosis by monoclonal antibodies. N Engl J Med. 1981 Feb 19;304(8):460–462. doi: 10.1056/NEJM198102193040804. [DOI] [PubMed] [Google Scholar]
  8. Enck R. E., Betts R. F., Brown M. R., Miller G. Viral serology (hepatitis B virus, cytomegalovirus, Epstein-Barr virus) and abnormal liver function tests in transfused patients with hereditary hemorrhagic diseases. Transfusion. 1979 Jan-Feb;19(1):32–38. doi: 10.1046/j.1537-2995.1979.19179160263.x. [DOI] [PubMed] [Google Scholar]
  9. Engers H. D., Louis J. A., Zubler R. H., Hirt B. Inhibition of T cell-mediated functions by MVM(i), a parvovirus closely related to minute virus of mice. J Immunol. 1981 Dec;127(6):2280–2285. [PubMed] [Google Scholar]
  10. Froebel K. S., Madhok R., Forbes C. D., Lennie S. E., Lowe G. D., Sturrock R. D. Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate? Br Med J (Clin Res Ed) 1983 Oct 15;287(6399):1091–1093. doi: 10.1136/bmj.287.6399.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gordon R. S., Jr Factor VIII products and disordered immune regulation. Lancet. 1983 Apr 30;1(8331):991–991. doi: 10.1016/s0140-6736(83)92115-3. [DOI] [PubMed] [Google Scholar]
  12. Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
  13. Jones P., Proctor S., Dickinson A., George S. Altered immunology in haemophilia. Lancet. 1983 Jan 15;1(8316):120–121. doi: 10.1016/s0140-6736(83)91758-0. [DOI] [PubMed] [Google Scholar]
  14. Kessler C. M., Schulof R. S., Goldstein A. L., Naylor P. H., Luban N. L., Kelleher J. F., Reaman G. H. Abnormal T-lymphocyte subpopulations associated with transfusion of blood-derived products. Lancet. 1983 Apr 30;1(8331):991–992. doi: 10.1016/s0140-6736(83)92116-5. [DOI] [PubMed] [Google Scholar]
  15. Kornfeld H., Vande Stouwe R. A., Lange M., Reddy M. M., Grieco M. H. T-lymphocyte subpopulations in homosexual men. N Engl J Med. 1982 Sep 16;307(12):729–731. doi: 10.1056/NEJM198209163071206. [DOI] [PubMed] [Google Scholar]
  16. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  17. Lechner K., Niessner H., Bettelheim P., Deutsch E., Fasching I., Fuhrmann M., Hinterberger W., Korninger C., Neumann E., Liszka K. T-cell alterations in hemophiliacs treated with commercial clotting factor concentrates. Thromb Haemost. 1983 Aug 30;50(2):552–556. [PubMed] [Google Scholar]
  18. Lederman M. M., Ratnoff O. D., Scillian J. J., Jones P. K., Schacter B. Impaired cell-mediated immunity in patients with classic hemophilia. N Engl J Med. 1983 Jan 13;308(2):79–83. doi: 10.1056/NEJM198301133080205. [DOI] [PubMed] [Google Scholar]
  19. Lee C. A., Janossy G., Ashley J., Kernoff P. B. Plasma fractionation methods and T-cell subsets in haemophilia. Lancet. 1983 Jul 16;2(8342):158–159. doi: 10.1016/s0140-6736(83)90136-8. [DOI] [PubMed] [Google Scholar]
  20. Lee C. A., Kernoff P. B., Karayiannis P., Waters J., Thomas H. C. Abnormal T-lymphocyte subsets in hemophilia: relation to HLA proteins in plasma products. N Engl J Med. 1984 Apr 19;310(16):1058–1058. doi: 10.1056/NEJM198404193101617. [DOI] [PubMed] [Google Scholar]
  21. Luban N. L., Kelleher J. F., Jr, Reaman G. H. Altered distribution of T-lymphocyte subpopulations in children and adolescents with haemophilia. Lancet. 1983 Mar 5;1(8323):503–505. doi: 10.1016/s0140-6736(83)92193-1. [DOI] [PubMed] [Google Scholar]
  22. Marx J. L. New disease baffles medical community. Science. 1982 Aug 13;217(4560):618–621. doi: 10.1126/science.7089584. [DOI] [PubMed] [Google Scholar]
  23. Menitove J. E., Aster R. H., Casper J. T., Lauer S. J., Gottschall J. L., Williams J. E., Gill J. C., Wheeler D. V., Piaskowski V., Kirchner P. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Engl J Med. 1983 Jan 13;308(2):83–86. doi: 10.1056/NEJM198301133080206. [DOI] [PubMed] [Google Scholar]
  24. Morris L., Distenfeld A., Amorosi E., Karpatkin S. Autoimmune thrombocytopenic purpura in homosexual men. Ann Intern Med. 1982 Jun;96(6 Pt 1):714–717. doi: 10.7326/0003-4819-96-6-714. [DOI] [PubMed] [Google Scholar]
  25. Mortimer P. P., Luban N. L., Kelleher J. F., Cohen B. J. Transmission of serum parvovirus-like virus by clotting-factor concentrates. Lancet. 1983 Aug 27;2(8348):482–484. doi: 10.1016/s0140-6736(83)90512-3. [DOI] [PubMed] [Google Scholar]
  26. Ramsey R. B., Palmer E. L., McDougal J. S., Kalyanaraman V. S., Jackson D. W., Chorba T. L., Holman R. C., Evatt B. L. Antibody to lymphadenopathy-associated virus in haemophiliacs with and without AIDS. Lancet. 1984 Aug 18;2(8399):397–398. doi: 10.1016/s0140-6736(84)90559-2. [DOI] [PubMed] [Google Scholar]
  27. Ratnoff O. D., Menitove J. E., Aster R. H., Lederman M. M. Coincident classic hemophilia and "idiopathic" thrombocytopenic purpura in patients under treatment with concentrates of antihemophilic factor (factor VIII). N Engl J Med. 1983 Feb 24;308(8):439–442. doi: 10.1056/NEJM198302243080808. [DOI] [PubMed] [Google Scholar]
  28. Rickard K. A., Joshua D. E., Campbell J., Wearne A., Hodgson J., Kronenberg H. Absence of AIDS in haemophiliacs in Australia treated from an entirely voluntary blood donor system. Lancet. 1983 Jul 2;2(8340):50–51. doi: 10.1016/s0140-6736(83)90037-5. [DOI] [PubMed] [Google Scholar]
  29. Suffredini A., Qureshi G. D. Concomitant hemophilia and thrombocytopenia. JAMA. 1982 May 14;247(18):2497–2498. [PubMed] [Google Scholar]
  30. deShazo R. D., Andes W. A., Nordberg J., Newton J., Daul C., Bozelka B. An immunologic evaluation of hemophiliac patients and their wives. Relationships to the acquired immunodeficiency syndrome. Ann Intern Med. 1983 Aug;99(2):159–164. doi: 10.7326/0003-4819-99-2-159. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES