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Chapter 32 Acquired Disorders of Red Cell, White Cell, and Platelet Production 427

receptor for the virus is the P antigen, a blood group antigen also pathogenesis of the PRCA in this setting may vary and includes
66
responsible for the agglutination reaction that occurs in the presence autoantibody-mediated erythroid inhibition, autoantibody directed
67
of the virus. Detection of parvovirus B19–specific IgM without against erythropoietin, and CTL-mediated killing of erythroid
antiparvovirus B19 IgG, supports the diagnosis of acute infection, precursors. 64
whereas the parvovirus B19–specific IgG suggests immunity. Addi-
tion of parvovirus B19 in vitro to cultures of erythroid progenitor
cells completely abolishes erythroid colony formation. Primary infec- Drug-Induced PRCA
tion causes lifelong immunity; however, it is possible that a latent
virus may persist in a healthy individual for years. Various chemical agents and drugs have been associated with PRCA.
A transient aplastic crisis is a typical complication of a primary The mechanisms responsible for erythroid inhibition may be diverse
parvovirus B19 infection in patients with increased red cell turnover depending on the offending agent (Table 32.2) but may include
(usually chronic hemolysis, e.g., hemoglobinopathies, and hereditary induction of antibodies targeting the drugs or drugs bound to cellular
red blood cell [RBC] membrane disorders, e.g., hereditary spherocy- and plasma proteins. Another possible mechanism involves drug-
tosis). In typical cases, acute reticulocytopenia results in a sudden mediated triggering of T-cell responses, or direct toxicity to the ery-
drop in hemoglobin (Hb)/hematocrit levels as RBC destruction is throid series as seen with diphenylhydantoin. 68
not supported by a suppressed marrow. Occasionally, characteristic
giant pronormoblasts may be seen in marrow aspirates (Fig. 32.2).
Aplastic crisis is often self-limiting with the evolution of a protective Erythropoietin Antibody–Associated PRCA
IgG response. Viral titers in the serum of affected patients may
be high. Recombinant erythropoietin is used in the treatment of anemia
A more chronic form, parvovirus B19–related PRCA, may develop of various origins, including anemia of chronic disease, renal disease,
in immunocompromised patients as, for example, in acquired immu- and a variety of bone marrow failure syndromes, particularly myelo-
nodeficiency syndrome (AIDS). In such cases, IVIg can produce dysplastic syndrome (MDS). Cases of PRCA have developed
remarkable responses. High doses of IVIg are required (>2 g/kg)
because an insufficient dose may not produce the desired effect. DNA
dot blot hybridization is the best diagnostic test for the detection of
viremia. Parvovirus B19 can also be detected by polymerase chain TABLE Drugs and Chemicals Implicated in Pure Red
reaction (PCR), a routinely available test, but this method may 32.2 Cell Aplasia
provide a high rate of false-positive results. However, if negative, it Alemtuzumab 69 Isoniazid 92–94
excludes B19 parvovirus–mediated disease. Improved tests have been Allopurino 70,71 Lamivudine 95
developed that allow for the detection of neutralizing antibodies and α-Methyldopa 72 Linezolid 96
infectivity of parvovirus B19. Several other viral infections, including Aminopyrine 73 Maloprim 97
viral hepatitis (A and C), Epstein-Barr virus (EBV), cytomegalovirus Azathioprine 74,75 Mycophenolate mofetil 98
(CMV), human T-Lymphotropic virus (HTLV)-1, and human Benzene 76 Penicillin 99
immunodeficiency virus (HIV) have been implicated as causative Carbamazepine 77 Phenylbutazone 100
agents of PRCA. Little is known about the exact mechanisms under- Cephalothin 78 Phenytoin 68,101,102
lying these disorders, but they likely involve T cell–mediated suppres- Chloramphenicol 79 Procainamide 103–105
sion as observed during HTLV-1 infection and EBV or Chlorpropamide 80,81 Ribavirin 98,106
antibody-mediated destruction of RBC precursors, as in hepatitis Cladribine 82 Rifampicin 107
C–induced PRCA. Clopidogrel Sulfasalazine 108,109
Cotrimoxazole 83 Sulfathiozole 110
Connective Tissue Disease–Associated PRCA D-Penicillinamine 84 Sulindac 111 112
Erythropoietin
Tacrolimus
43,44
Estrogens 85 Thiamphenicol 113
The majority of connective tissue diseases associated with PRCA Fludarabine 86 Ticlopidine 114,115
are autoimmune in nature. Several rheumatologic diseases have FK506 87 Valproic acid 116,106
been associated with PRCA, including adult-onset Still disease, 58,59 Gold 88 Zidovudine 117
60
41
dermatomyositis, mixed connective tissue disease, polymyosi- Halothane 89
61
tis, rheumatoid arthritis, 38,62 Sjögren syndrome, 39,40,63 systemic Interferon-α 90,91
lupus erythematosus and antiphospholipid syndrome. 37,64,65 The

Fig. 32.2 PARVOVIRUS B19–MEDIATED PURE RED CELL APLASIA.