Abstract
To clarify the mechanisms of thrombocytopenia observed in patients with chronic hepatitis B treated with interferon. We studied six patients with chronic active hepatitis B who received intramuscular injections of natural interferon-alpha (3 or 5 million IU/day) for 4 weeks. Peripheral blood platelet counts, bone marrow findings, and platelet kinetics, determined using111In-labeled platelets, were analyzed. Platelets decreased significantly 1 week after the beginning of treatment and remained decreased until the completion of treatment. The number of nucleated cells and megakaryocytes in bone marrow decreased in three of five patients studied during treatment. The kinetic study showed platelet survival time to be 8.1±1.3 days (range, 5.8–10.0). One day after platelet injection, platelets accumulated predominantly in the splenic area in all patients, whereas hepatic accumulation was predominant 7 days after injection in three of the six patients. Thrombocytopenia during interferon treatment arises from the inhibition of stem cell proliferation and differentiation in the bone marrow and from the capture of platelets by the liver.
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Greenberg BH, Pollard BR, Lutwick IL, et al. Effect of human leukocyte interferon on hepatits B virus infection in patients with chronic active hepatitis. New Engl J Med 1976;295:511–522.
Hoofnagle JH, Mulen KD, Jones DB, et al. Treatment of chronic non-A, non B hepatitis with recombinant human alpha interferon. New Engl J Med 1986;315:1575–1578.
Davis GL, Balart LA, Shiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alpha. N Engl J Med 1989;321:1501–1506.
Hoshino U, Suou T, Kawasaki H. Evaluation of side effects of interferon therapy by questionnaire in chronic hepatitis C. Acta Hepatol Jap 1995;36:506–510.
Ernstoff MS, Kirkwood JM. Changes in the bone marrow of cancer patients treated with recombinant interferon alpha-2. Am J Med 1984;76:593–596.
van't Hull E, Schellekens H, Löenberg B, et al. Influence of interferon preparations on the proliferative capacity of human and mouse bone marrow cells in vitro. Cancer Res 1978;38:911–914.
Hansson M, Beran M, Andersson B, et al. Inhibition of in vitro granulopoiesis by autologous allogeneic human NK cells. J Immunol 1982;129:126–132.
Heumann HA, Fauser AA. Effect of interferon on pluripotent hemopoietic progenitors (CFU-GEMM) derived from human bone marrow. Exp Hematol 1982;10:587–590.
Mazur EM, Richtsmeier WJ, South K. Alpha-interferon: Differential suppression of colony growth from human erythroid, myeloid, and megakaryocytic hematopoietic progenitor cells. J Int Res 1986;6:199–206.
Talpaz M, Spitzer G, Hittelman W, et al. Changes in granulocytemonocyte colony-forming cells among leulocyte-interferontreated chronic myelogenous leukemia patients. Exp Hematol 1986;14:668–671.
Ganser A, Carlo-Stella C, Greher J, et al. Effect of recombinant interferons alpha and gamma on human bone marrow-derived megakaryocytic progenitor cells. Blood 1987;70:1173–1179.
Abdi EA, Brien W, Venner PM. Auto-immune thrombocytopenia related to interferon therapy. Scand J Haematol 1986;36:515–519.
McLaughlin P, Talpaz M, Quesada JR, et al. Immune thrombocytopenia following α-interferon therapy in patients with cancer. JAMA 1985;254:1353–1354.
Terada H. Structure of platelets and megacaryocytes. Atlas of clinical examination. Blood 1978;2:78–86.
Dewanjee MK, Rao SA, Didisheim P. Indium-111 tropolone, a new high affinity platelet label: Preparation and evaluation of labeling parameters. J Nucl Med 1981;22:981–987.
ICSH panel on diagnostic application of radioisotopes in hematology: Recommended methods for radioisotope platelet survival studies. Blood 1977;50:1137–1144.
Hino K. Clinical pharmacology of interferon α and β. Biomed Therapeut 1993;27:1185–1192.
Thakur ML, Welch MJ, Joist G, et al. Indium-111 labeled platelets. Studies on preparation and evaluation of in vitro and in vivo function. Thromb Res 1976;9:345–357.
Klonizakis I, Peters AM, Fitzpatrick ML, et al. Radionuclide distribution following injection of,111Indium-labelled platelets. Br J Haematol 1980;46:595–602.
Toghill PJ, Green S. Platelet dynamics in chronic liver disease using the111Indium oxine label. Gut 1983;24:49–52.
Schmidt KG, Rasmussen JW, Bekker C, et al. Kinetics and in vivo distribution of111In-labeled autologous platelets in chronic hepatic disease: Mechanisms of thrombocytopenia. Scand J Haematol 1985;34:39–46.
Schmidt KG, Rasmussen JW. Kinetics and distribution in vivo of111In-labelled autologous platelets in idiopathic thrombocytopenic purpura. Scand J Haematol 1985;34:47–56.
Peters AM, Saverymuttu SH, Bell RN, Lavender JP. The kinetics of short-lived indium-111 radiolabelled platelets. Scand J Haematol 1985;34:137–145.
Peters AM, Saverymuttu SH, Malik F, et al. Intrahepatic kinetics of indium-111-labelled platelets. Thromb Haemost 1985;54:595–598.
Louwes H, Beekhuis H, Goedemans WTH, et al.111Intropolonate labelled platelets; studies in normals and in patients with thrombocytopenia. Eur J Nucl Med 1987;13:47–51.
Aoki Y, Hirai K, Tanikawa K. Mechanism of thrombocytopenia in liver cirrhosis: Kinetics of indium-111 tropolone labelled platelets. Eur J Nucl Med 1993;20:123–129.
Heyns AP, Löter MG, Badenhorst PN, et al. Kinetics and in vivo redistribution of111Indium-labelled human platelets after intravenous protamine sulfate. Thromb Haemost 1980;44:65–68.
Cornacoff JB, Hebert LA, Smead WL, et al. Primate erythrocyteimmune complex-clearing mechanism. J Clin Invest 1983;71:236–247.
Karas SP, Rosse WF, Kurlander RJ. Characterization of IgG-Fc receptor on human platelets. Blood 1982;60:1277.
Pace JL, Russell SW, LeBlanc PA, et al. Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing. J Immunol 1985;134:977–981.
Prieto J, Yuste JR, Beloqui Q, et al. Anticardiolipin antibodies in chronic hepatitis C: Implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology 1996;23: 199–204.
Herbert JM, Savi P, Laplace MC, et al. IL-4 and IL-13 exhibit comparable abilities to reduce pyrogen-induced expression of procoagulant activity in endothelial cells monocytes. FEBS Lett 1993;328:268–270.
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Sata, M., Yano, Y., Yoshiyama, Y. et al. Mechanisms of thrombocytopenia induced by interferon therapy for chronic hepatitis B. J Gastroenterol 32, 206–210 (1997). https://doi.org/10.1007/BF02936369
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DOI: https://doi.org/10.1007/BF02936369