Tuberculosis pp 213-230 | Cite as

Hematologic Findings in Mycobacterial Infections Among Immunosuppressed and Immunocompetent Patients

  • Görgün Akpek


The relationship between hematologic abnormalities and mycobacterial infections dates back to the beginning of the 20th Century. Flinn and his colleagues suggested at that time that the change in hematologic parameters is the earliest finding of tuberculosis (TB) (Flinn and Finn 1929). The authors said ’In connection with the above studies we have formed the impression that an extension of the pathologic process in a tuberculosis lung usually manifests itself first in the blood picture, later by physical signs and x-ray, and often last of all by Symptoms.’ Before embarking upon a general discussion of hematologic manifestations of mycobacterial infections, I would like to present two cases that were previously discussed at the Medical Staff Conference in the University of San Francisco, California, USA, in 1967. These cases have certain features of the history and clinical findings of TB, in particular, the striking difference in the hematological manifestations between the two cases. A brief summary about the demographics and clinical presentation of Mycobacterium TB infection is included thereafter.


Thrombotic Thrombocytopenic Purpura Immune Thrombocytopenic Purpura Mycobacterial Infection Mycobacterium Avium Complex Purify Protein Derivative 
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  1. Aboulafia DM, Mitsuyasu RT (1991) Hematologic abnormalities in AIDS. Hematol Oncol Clin North Am 5:195–214PubMedGoogle Scholar
  2. Akhtar AJ, Crompton GK, Schonell ME (1968) Para-aminosalicylic acid as a cause of intestinal malabsorption. Tubercle 49:328–331PubMedGoogle Scholar
  3. Akpek G et al (2001) Bone marrow aspiration, biopsy, and culture in the evaluation of HIV-infected patients for invasive mycobacteria and histoplasma infections. Am J Hematol 67:100–106PubMedGoogle Scholar
  4. Al-Majed SA et al (1995) Tuberculosis presenting as immune thrombocytopenic purpura. Acta Haematol 94:135–138PubMedGoogle Scholar
  5. Argiris A, Maun N, Berliner N (1999) Mycobacterium avium complex inclusions mimicking Gaucher’s cells. N Engl Med 340:1372Google Scholar
  6. Barnes PF (1997) Rapid diagnostic tests for tuberculosis: progress but no gold Standard. Am J Respir Crit Care Med 155:1497–1498PubMedGoogle Scholar
  7. Barreto JA et al (1993) Isolation of Mycobacterium avium complex from bone marrow aspirates of AIDS patients in Brazil. J Infect Dis 168:777–779PubMedGoogle Scholar
  8. Basu S, Mohan H, Malhotra H (2000) Pancytopenia due to hemophagocytic Syndrome as the presenting manifestation of tuberculosis. J Assoc Physicians India 48:845–846PubMedGoogle Scholar
  9. Benito N et al (1997) Bone Marrow Biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency Syndrome. Arch Intern Med 57:1577–1580Google Scholar
  10. Benson CA, Ellner JJ (1993) Mycobacterium avium complex infection and AIDS: advances in theory and practice. Clin Infect Dis 17:7PubMedGoogle Scholar
  11. Bhargava V, Farhi DC (1988) Bone marrow granulomas: clinicopathologic findings in 72 cases and review of the literature. Hematol Pathol 2:43–50PubMedGoogle Scholar
  12. Boots RJ, Roberts AW, McEvoy D (1992) Immune thrombocytopenia complicating pulmonary tuberculosis. Case report and investigation of mechanism. Thorax 47:396–397Google Scholar
  13. Bozoky G et al (1997) Hematologic abnormalities in pulmonary tuberculosis. Orv Hetil 138:1053–1056PubMedGoogle Scholar
  14. Brooks BJ Jr, Alvarez S, Yoder L (1990) Leukopenia secondary to Mycobacterium leprae. J La State Med Soc 142:35–36PubMedGoogle Scholar
  15. Cameron SJ (1974) Tuberculosis and the blood: a Special relationship. Tubercle 5:65–72Google Scholar
  16. Casanova-Roman M et al (2002) Deep venous thrombosis associated with pulmonary tuberculosis and transient protein S deficiency. Scand J Infect Dis 34:393–394PubMedGoogle Scholar
  17. Castella A et al (1985) The bone marrow in AIDS: a histologic, hematologic and microbiologic study. Am J Clin Pathol 84: 425PubMedGoogle Scholar
  18. Centers for Disease Control and Prevention (2000) Reported tuberculosis in the United States, 1999. Centers for Disease Control and Prevention, AtlantaGoogle Scholar
  19. Charfi MR et al (1998) Disseminated tuberculosis in nonimmunocompromised host: three case reports. Rev Med Interne 19:917–920PubMedGoogle Scholar
  20. Chia YC, Machin SJ (1979) Tuberculosis and severe thrombocytopenia. Br J Clin Pract 33:55–56PubMedGoogle Scholar
  21. Chin DP et al (1994) The impact of Mycobacterium avium complex bacteremia and its treatment on survival of AIDS patients-a prospective study. J Infect Dis 170:578–584PubMedGoogle Scholar
  22. Ciaudo M et al (1994) Revisited indications for bone marrow examinations in HIV-infected patients. Eur J Haematol 53: 168–174PubMedGoogle Scholar
  23. Cockcroft DW et al (1976) Miliary tuberculosis presenting with hyponatremia and thrombocytopenia. Can Med AssocJ 115:871–873Google Scholar
  24. Cohen RJ et al (1983) Occult infections with M. intracellulare in bone marrow biopsy specimens from patients with AIDS. N Engl J Med 308:1475Google Scholar
  25. Condos R et al (1996) Peripheral-blood-based PCR assay to identify patients with active pulmonary tuberculosis. Lancet 347:1082–1085PubMedGoogle Scholar
  26. Corr WP, Kyle RA, Bowie EJW (1964) Hematologic changes in tuberculosis. Am J Med Sei 248:709–714Google Scholar
  27. Coyle TE (1997) Hematologic complications of human immunodeficiency virus infection and AIDS. In: Gold JWM, Telzak EE, White DA (eds) Management of the HIV-infected patient, part II. Infections and malignancies associated with HIV infection. Saunders, Philadelphia, pp 449–470 (Medical clinics of North America, vol 81)Google Scholar
  28. Daley CL, Small PM, Schecter GF (1992) An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. N Engl J Med 36:231–235Google Scholar
  29. Dallalio G et al (1999) Cytokine and cytokine reeeptor concentrations in bone marrow supernatant from patients with HIV: correlation with hematologic parameters. J Invest Med 47:477–483Google Scholar
  30. Di Perri G, Danzi MC, DeChecchi G (1989) Nosocomial epidemic of active tuberculosis among HIV-infected patients. Lancet 2:1502–1504PubMedGoogle Scholar
  31. Dutt AK, Moers D, Stead WW (1983) Undesirable side effects of isoniazid and rifampin in largely twice-weekly shortcourse chemotherapy for tuberculosis. Am Rev Respir Dis 128:419–424PubMedGoogle Scholar
  32. Dye C et al (1999) Consensus Statement: global bürden of tuberculosis: estimated ineidence, prevalence, and mortal-ity by country: WHO Global Surveillance and Monitoring Project. JAMA 282:677–686PubMedGoogle Scholar
  33. Eliopoulos G et al (1992) Tuberculosis associated hemophagocytic Syndrome complicated with severe bone marrow failure and disseminated intravascular coagulation. Nouv Rev Fr Hematol 34:273–276PubMedGoogle Scholar
  34. Ellaurie M, Rubinstein A (1995) Elevated tumor necrosis factor alpha in association with severe anemia in human immunodeficiency virus infection and mycobacterium avium intracellulare infection. Pediatr Hematol Oncol 12: 221–230PubMedGoogle Scholar
  35. Ellner JJ, Goldberger MJ, Parenti DM (1991) Mycobacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. J Infect Dis 163:1326–1335PubMedGoogle Scholar
  36. Fahal IH et al (1992) Thrombotic thrombocytopenic purpura due to rifampicin. Br Med J 304:882Google Scholar
  37. Flinn JW, Finn RS (1929) Annu Rev Tuberculosis 20:347Google Scholar
  38. French AL, Benator DA, Gordin FM (1997) Nontuberculous mycobacterial infections. In: God JWM, Telzak EE, White DA (eds) The management of the HIV-infected patient, part II. Infections and malignancies associated with HIV infection. Saunders, Philadelphia, pp 361–379 (Medical clinics of North America, vol 81)Google Scholar
  39. Fujita M et al (1997) Disseminated intravascular coagulation associated with pulmonary tuberculosis. Intern Med 36: 218–220PubMedGoogle Scholar
  40. Gascon P, Sathe SS, Rameshwar P (1993) Impaired erythropoiesis in the acquired immunodeficiency Syndrome with disseminated Mycobacterium avium complex. Am J Med 94:41–48PubMedGoogle Scholar
  41. Ghobrial MW, Albornoz MA (2001) Immune thrombocytopenia: a rare presenting manifestation of tuberculosis. Am J Hematol 67:139–143PubMedGoogle Scholar
  42. Glasser RM, Walker RI, Herion JC (1970) The significance of hematologic abnormalities in patients with tuberculosis. Arch Intern Med 125:691–695PubMedGoogle Scholar
  43. Gogna A et al (1999) Tuberculosis presenting as deep vein thrombosis. Postgrad Med J 75:104–105PubMedGoogle Scholar
  44. Goldfine ID et al (1969) Consumption coagulopathy in miliary tuberculosis. Ann Intern Med 71:775–777PubMedGoogle Scholar
  45. Havlick JA et al (1992) Disseminated mycobacterium avium complex infection: clinical identifiers and epidemiologic trends. J Infect Dis 165:577–580Google Scholar
  46. Havlir DV, Barnes PF (1999) Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 340:367–373PubMedGoogle Scholar
  47. Hernandez-Maraver D et al (1996) Immune thrombocytopenic purpura due to disseminated tuberculosis. Acta Haematol 96:266PubMedGoogle Scholar
  48. Hirsch CS et al (1996) Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production. Proc Natl Acad Sei USA 93:3193–3198Google Scholar
  49. Horsburgh CR et al (1994) Predictors of survival in patients with AIDS and disseminated mycobacterium avium complex disease. J Infect Dis 170:573–577PubMedGoogle Scholar
  50. Ip M, Cheng KP, Cheung WC (1991) Disseminated intravascular coagulopathy associated with rifampicin. Tuberde 72:291–293Google Scholar
  51. Iseman MD (2000) Tuberculosis in relation to human immunodeficiency virus and acquired immunodeficiency Syndrome. A clinician’s guide to tuberculosis. Lippincott Williams and Wilkins, Philadelphia, pp 199–252Google Scholar
  52. Ishida T et al (1998) Pulmonary Mycobacterium avium disease in a young patient with idiopathic CD4+ T lymphocytopenia. Intern Med 37:622–624PubMedGoogle Scholar
  53. Jenss H, Ostendorf P (1980) Leukopenia and consumption coagulopathy in miliary tuberculosis. Schweiz Med Wochenschr 110:1208–1213PubMedGoogle Scholar
  54. Jones BE et al (1993) Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis 148: 1292–1297PubMedGoogle Scholar
  55. Jones BE et al (1997) CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis. Clin Infect Dis 24:988–991PubMedGoogle Scholar
  56. Jurak SS, Aster R, Sawaf H (1983) Immune thrombocytopenia associated with tuberculosis. Clin Pediatr (Phila) 22: 318–319Google Scholar
  57. Kavesh NG, Holzman RS, Seidlin M (1989) The combined toxicity of azidothymidine and antimycobacterial agents. A retrospective study. Am Rev Respir Dis 139:1094–1097PubMedGoogle Scholar
  58. Keung YK et al (1999) Mycobacterium tuberculosis infection masquerading as diffuse alveolar hemorrhage after autologous stem cell transplant. Bone Marrow Transplant 23:737–738PubMedGoogle Scholar
  59. Kilby JM et al (1998) The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections. Am J Med 104:123–128PubMedGoogle Scholar
  60. Kramers C et al (1992) Sweet’s Syndrome as the presenting symptom of hairy cell leukemia with concomitant infection by Mycobacterium kansasii. Ann Hematol 65:55–58PubMedGoogle Scholar
  61. Krauss JS, Walker DH (1979) Miliary tuberculosis and consumption of clotting factors by multifocal vasculopathic coagulation. South Med J 72:1479–1481PubMedGoogle Scholar
  62. Krishnaswamy V (1969) Disseminated tuberculosis presenting as a bleeding disorder. J Indian Med Assoc 53:85–87PubMedGoogle Scholar
  63. Levy M, Cooper BA (1964) Thrombocytopenic purpura associated with tuberculous lymphadenitis. Can Med Assoc J 90:373–374PubMedGoogle Scholar
  64. Maartens G, Willcox PA, Benatar SR (1990) Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 89:291–296PubMedGoogle Scholar
  65. Mandell GL et al (2000) Principles and practice of infectious diseases. Mycobacterial infectionsGoogle Scholar
  66. Maurice PD et al (1988) Mycobacterium avium-intracellulare infection associated with hairy-cell leukemia. Arch Dermatol 124:1545–1549PubMedGoogle Scholar
  67. Mavligit GM, Binder RA, Crosby WH (1972) Disseminated intravascular coagulation in miliary tuberculosis. Arch Intern Med 130:388–389PubMedGoogle Scholar
  68. Medd WE, Hayhoe FGJ (1955) Tuberculous miliary necrosis with pancytopenia. Quart J Med 24:351PubMedGoogle Scholar
  69. Medical Staff Conference (1967) Hematologic manifestations of tuberculosis. Calif Med 106:215–221Google Scholar
  70. Moore M, McCray E, Onorato IM (1999) TB-AIDS versus non AIDS TB cases, United States, 1993–1997. Int J Tuberc Lung Dis S20–S20 abstractGoogle Scholar
  71. Modi T, Narita N (1998) Mycobacterial infection in patients with hematologic disorders. Nippon Rinsho 56:3209–3211Google Scholar
  72. Nichols L et al (1991) Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency Syndrome. Arch Pathol Lab Med 115:1125–1132PubMedGoogle Scholar
  73. Nightingale SD et al (1992) Incidence of Mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. J Infect Dis 165:1082–1085PubMedGoogle Scholar
  74. Northfelt DW et al (1991) The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection. J Acquir Immune Defic Syndr 4:659–666PubMedGoogle Scholar
  75. O’Brien JR (1954) Nonreactive tuberculosis. J Clin Pathol 7: 216–225PubMedGoogle Scholar
  76. O’Hara CJ (1989) The lymphoid and hematopoietic Systems. In: Harawi SJ, O’Hara CJ (eds) Pathology and pathophysiology of AIDS and HIV-related diseases. iMosby, St Louis, pp 150–164Google Scholar
  77. Onwubalili JK, Edwards EJ, Palmer L (1987) T4 lymphophenia in human tuberculosis. Tubercle 68:195PubMedGoogle Scholar
  78. O’Reilly RA (1998) Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. West J Med 169:78–87PubMedGoogle Scholar
  79. Oswald NC (1963) Acute tuberculosis and granulocytic disorders. Br Med J 2:1489–1496PubMedGoogle Scholar
  80. Otsuji A et al (1990) Transient large granulär lymphocytosis associated with pulmonary tuberculosis: a case report. Rinsho Ketsueki 31:1955–1959PubMedGoogle Scholar
  81. Pavithran K, Vijayalekshmi N (1993) Thrombocytopenic purpura with tuberculous adenitis. Indian J Med Sei 47: 239–240Google Scholar
  82. Pene F et al (2001) Septic shock and thrombotic microangiopathy due to Mycobacterium tuberculosis in a nonimmunocompromised patient. Arch Intern Med 161: 1347–1348PubMedGoogle Scholar
  83. Perez de Llano LA, Soilan del Cerro JL, Garcia Pais MJ (1998) Imune thrombocytopenic purpura as presenting form of miliary tuberculosis. Arch Broncho Pneumol 34:411–412Google Scholar
  84. Pierce M et al (1996) A randomized trial of clarithromyein as prophylaxis as prophylaxis against Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency Syndrome. N Engl J Med 335:384–391PubMedGoogle Scholar
  85. Riley UB et al (1995) Detection of mycobacteria in bone marrow biopsy speeimens taken to investigate pyrexia of unknown origin. J Clin Pathol 48:706–709PubMedGoogle Scholar
  86. Roberts PD, Hoffbrand AV, Mollin DL (1966) Iron and folate metabolism in tuberculosis. Br Med J 5507:198–202Google Scholar
  87. Rosenberg MJ, Rumans LW (1978) Survival of a patient with pancytopenia and disseminated coagulation associated with miliary tuberculosis. Chest 73:536–539PubMedGoogle Scholar
  88. Rosenblum LS et al (1994) Effect of HIV infection and tuberculosis on hospitalizations and cost of care for young adults in the United States, 1985 to 1990. Ann Intern Med 121:786–792PubMedGoogle Scholar
  89. Rosenthal T, Pitlik S, Michaeli D (1975) Fatal undiagnosed tuberculosis in hospitalized patients. J Infect Dis 131 [Suppl]:S51–S56PubMedGoogle Scholar
  90. Salzman SH et al (1992) The role of bronchoscopy in the diagnosis of pulmonary tuberculosis in patients at risk for HIV infection. Chest 102:143–146PubMedGoogle Scholar
  91. Sehonanda A, Choi YJ, Blum S (1996) Changing patterns of autopsy findings among persons with acquired immunodeficiency Syndrome in an inner-city population. Arch Pathol Lab Med 120:459–464PubMedGoogle Scholar
  92. Selik RM, Chu SY, Ward JW (1995) Trends in infectious disease and cancers among persons dying of HIV infection in the United States from 1987 to 1992. Ann Intern Med 123:933–936PubMedGoogle Scholar
  93. Shafer RW et al (1991) Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine 70:384–397PubMedGoogle Scholar
  94. Shenkenberg TD, Rice L, Waddell CC (1982) Acquired PelgerHuet nuclear anomaly with tuberculosis. Arch Intern Med 142:153–154PubMedGoogle Scholar
  95. Singh KJ et al (2001) Significance of haematological manifestations in patients with tuberculosis. J Assoc Physicians India 49:790–794Google Scholar
  96. Singh SP et al (1986) Tubercular lymphadenitis with purpura. J Indian Med Assoc 84:247–249PubMedGoogle Scholar
  97. Skopinski S et al (2001) Mycobacterium avium complex septicemia: a new cause of thrombocytopenic thrombotic purpura. Rev Med Interne 22:400–401PubMedGoogle Scholar
  98. Slavin RE, Walsh TJ, Pollack AD (1980) Late generalized tuberculosis: a clinical pathologic analysis and comparison of 100 cases in the preantibiotic and antibiotic eras. Medicine (Baltimore) 59:352–366Google Scholar
  99. Solis OC, Belmonte AH, Ramaswamy G (1986) Pseudo-Gaucher cells in Mycobacterium avium-intracellulare infection in the acquired immunodeficiency Syndrome (AIDS). Am J Clin Pathol 85:233PubMedGoogle Scholar
  100. Stein DS, Libertin CR (1990) Disseminated intravascular coagulation in association with cavitary tuberculosis. South Med J 83:60–63PubMedGoogle Scholar
  101. Talbot S et al (1998) Mediastinal nodal tuberculosis presenting as immune thrombocytopenia. Aust NZ J Med 28:465–466Google Scholar
  102. Torriani FJ et al (1994) Autopsy findings in AIDS patients with mycobacterium avium complex bacteremia. J Infect Dis 170:1601–1605PubMedGoogle Scholar
  103. Torriani FJ et al (1996) Disseminated Mycobacterium avium complex: correlation between blood and tissue burden. J Infect Dis 173:942–949PubMedGoogle Scholar
  104. Toscano V et al (1995) Thrombotic thrombocytopenic purpura associated with primary tuberculosis. Infection 23:58–59PubMedGoogle Scholar
  105. Tulliez M (1976) Bone marrow’s histopathology in tuberculosis of the hematopoietic organs. Pathol Biol (Paris) 24:699–711Google Scholar
  106. Turett GS, Telzak EE (1994) Normalization of CD4 + T-lymphocyte depletion in persons without HIV infection treated for tuberculosis. Chest 105:1335PubMedGoogle Scholar
  107. Uetake T et al (1990) Clinicopathological study of miliary tuberculosis in patients with hematologic disease. Kekkaku 65:273–283PubMedGoogle Scholar
  108. Ugo V et al (1996) Myelodysplasia and tuberculosis. Bull Cancer 83:548–552PubMedGoogle Scholar
  109. Wendland T et al (2000) Strong alpha beta and gamma delta TCR response in a patient with disseminated Mycobacterium avium infection and lack of NK cells and monocytopenia. Immunol Lett 72:75–82PubMedGoogle Scholar
  110. White NW (1989) Venous thrombosis and rifampicin. Lancet 2:434–435PubMedGoogle Scholar
  111. Whitfield CL (1970) Hematologic abnormalities in tuberculous patients. Arch Intern Med 126:698PubMedGoogle Scholar
  112. Yang CW et al (1996) Tuberculosis-associated hemophagocytic Syndrome in a hemodialysis patient: case report and review of the literature. Nephron 72:690–692PubMedGoogle Scholar
  113. Yasuda Y et al (1994) A case of intractable pulmonary tuberculosis complicated by idiopathic thrombocytopenic purpura. Nippon Kyobu Geka Gakkai Zasshi 42: 2301–2305PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Görgün Akpek
    • 1
  1. 1.Greenebaum Cancer Center at University of Maryland School of MedicineBaltimoreUSA

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