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540 Part VI: The Erythrocyte Chapter 36: Pure Red Cell Aplasia 541

TRANSIENT APLASTIC CRISIS AND tropic for erythroid progenitor cells, mainly because of their P antigen
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or globoside, the receptor for entry of B19 into the cell
(Fig. 36–1).
TRANSIENT ERYTHROBLASTOPENIA Infection lyses the target cell and abrogates erythropoiesis in vitro and in
OF CHILDHOOD vivo. Reticulocytopenia probably accompanies B19 parvovirus infection
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in all infected persons. Anemia only manifests if red cell survival is
DEFINITION AND HISTORY decreased. Infection ordinarily is terminated by production of neutraliz-
ing antibodies to the virus (when such antibodies are absent, persistence
Temporary failure of erythropoiesis is clinically identical to pure red cell of the virus produces chronic pure red cell aplasia). B19 parvovirus may
aplasia except for spontaneous resolution of symptoms and of the labo- appear in epidemics of fifth disease in the normal population and of
ratory findings of normocytic and normochromic anemia and marrow transient aplastic crisis, for example, in hematology clinics specializing
erythroid hypoplasia, usually over the course of a few weeks. Erythro- in sickle cell disease. 74,75 In fifth disease, IgM antibody is present in the
cyte production is halted: (1) by acute primate erythroparvovirus 1 (B19 blood, and virus levels are either low or are not detectable. Symptoms and
parvovirus) infection, typically in the context of underlying hemolytic signs of a typical “slapped cheek” cutaneous eruption and arthralgia or
disease (called transient aplastic crisis); (2) in normal children, usually arthritis are secondary to antibody–virus immune complex deposition.
after an infection by another [unknown] childhood virus (transient ery- In contrast, in transient aplastic crisis, high concentrations of virus
throblastopenia of childhood); or (3) as a transient reaction to a drug. are present in the circulation, and patients do not develop fifth disease.
An anemic crisis was described in the 1940s first by Lyngar and In children with sickle cell disease, the incidence of B19 parvovirus
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then by Owren, Gasser, and Dameshek and Bloom in kindreds with infection was estimated at approximately 11 percent, and 75 percent of
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hereditary spherocytosis. Several children within a family suffered patients were infected by age 20 years. In this setting, parvovirus infec-
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anemic crises and exhibited low, rather than the usually high, reticu- tion was associated with transient aplastic crisis, a higher frequency of
locyte numbers. Transient aplastic crisis also was noted as a complica- fever, pain, acute chest syndrome, and acute splenic sequestration syn-
tion of sickle cell disease. 62,63 Marrow examination showed decrease or drome. As in normal individuals, parvovirus infection can be asymp-
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absence of erythroid precursor cells, and often giant erythroblasts. 60,61 tomatic in sickle cell disease. 77
An infectious etiology was suspected from the history of a preceding The origins of transient erythroblastopenia of childhood are
febrile illness in families and its simultaneous occurrence in siblings. poorly understood. An apparent viral prodrome is typical, and tem-
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After the serendipitous discovery of B19 parvovirus in a normal blood poral and seasonal clustering of cases may occur. 79–81 With rare excep-
donor, Pattison and colleagues screened large numbers of stored sera for tion, B19 parvovirus is not the etiology, 83,84 and no other virus has been
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evidence of recent infection. Immunoglobulin (Ig) M antibody or viral consistently implicated. Erythroid colony numbers (Chap. 32) usually
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antigen was found in the blood of Jamaican children in London, all of are low. An immune pathophysiology has been inferred from in vitro
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whom had transient aplastic crisis of sickle cell disease. B19 parvovirus experiments in which IgG from sera of patients inhibited erythropoie-
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later was established as the agent also responsible for fifth disease. In sis in the majority of cases. Cell-mediated mechanisms also may play
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the large cohort of sickle cell patients in Jamaica reported by Serjeant a causal role. In one report, T-cell depletion led to a dramatic increase
and colleagues, 66,67 virtually all episodes of transient aplastic crisis could in CFU-E formation. A possible relationship between transient ery-
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be linked to B19 parvovirus. In retrospect, red cell aplasias blamed on throblastopenia of childhood and inherited red cell aplasia has been
kwashiorkor, vitamin deficiency, bacterial infections, and chemical suggested by the clustering of polymorphic alleles in familial transient
exposures likely represented parvovirus infection. erythroblastopenia. 89
Gasser described erythroblastopenia in normal children who ulti- The same drugs implicated in chronic pure red cell aplasia apply to
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mately recovered ; the disease was recognized as an entity by Wranne transient erythropoietic failure. Laboratory investigations of red cell
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in the 1970s. Transient erythroblastopenia of childhood has an unclear aplasia secondary to diphenylhydantoin and rifampicin are consis-
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etiology but may represent a postviral immune-mediated syndrome. The tent with a hapten mechanism, in which serum antibody affects ery-
syndrome is rare and may be declining in incidence. 69 throid progenitor cells only in the presence of drug.
ETIOLOGY AND PATHOGENESIS CLINICAL FEATURES
B19 parvovirus, a small DNA virus, commonly infects humans. Most Transient aplastic crisis typically occurs in younger patients who are
of the adult population has IgG antibodies specific to B19. The virus is chronically anemic as a result of hereditary spherocytosis, sickle cell
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A B C
Figure 36–1. A and B. Giant early erythroblast precursors in the marrow aspirate of a patient with chronic pure red cell aplasia secondary to per-
sistent B19 parvovirus infection. Note the nuclear inclusions (darker nuclear shading) representing parvovirus infection. C. Marrow biopsy section.
The arrows point to binucleate erythroid precursor cell with nuclear inclusions representing parvovirus infection. (Reproduced with permission from
Lichtman’s Atlas of Hematology, www.accessmedicine.com.)

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