BRIEF CLINICAL OBSERVATIONS

propriate bone marrow transplantation or treatment with immunosuppressive agents. Recognition of the heterogeneity of FA s h o u l d e n a b l e more precise pathophysiologic categorization of the bone marrow failure syndromes. Ultimately, supplantation of DEB testing by more sensitive genetic linkage assays [5] may lead to the identification of FA heterozygotes with important disease susceptibilities within the spectrum of FA.

TABLEI HematologicIndicesofthePatientBeforeandDuringHerIllness

Hemoglobin (g/dL) Reticulocytes(x 109/L) Leukocytes(x 109/L) Platelets (x 109/L)

One Year Before Aplastic Crisis 8 -9.8 357

has been implicated as the probable cause [1]. Aplastic crisis is National Heart, Lung, and Blood most rarely due to extensive bone Institute Bethesda, Maryland marrow necrosis [2,3]. We report ARLEEN D. AUERBACH, Ph.D. a case of acute severe anemia asThe Rockefeller University sociated with extensive bone New York, New York ]VEAL S. YOUNG,M.D. marrow necrosis and serologicalNational Heart, Lung, and Blood ly documented parvovirus infecInstitute tion. Bethesda, Maryland A 24-year-old woman, known 1. Alter BP, Young NS. The bone marrow failure synto have typical homozygous SCD dromes. In: Nathan DG, Oski FA, editors. Hematolo(hemoglobin [Hb] S: 87.8%; HbF: 83/of infancy and childhood. Philadelphia: Saunders, 9%; HbA2: 3.2%), was admitted ]990. 2. Auerbach AD, Rogatko A, Schroeder-Kurth TM. for dizziness, diffuse bone pain, International Fanconi anemia registry: relation of dyspnea, and fever of 2-week duclinical symptoms to diepoxybutane sensitivity. ration. On admission, her temBlood 1989; 73: 391-6. 3. Estren S, Dameshek W. Familial hypoplastic aneperature was 40°C, she was dysmia of childhood. Report of eight cases in two famipneic at rest, and her arterial lies with beneficial effect of splenectomy in one blood gas values were as follows: case. Am J Dis Child ]947; 73: 671-87. 4. Alter BP, Frissora CL, Halperin DS, et aL Fan- pH 7.43, carbon dioxide tension coni's anaemia and pregnancy. Br J Haematol (PC02) 35 mm Hg, and oxygen 1991; 77: 410-8. tension (PO2) 61 mm Hg. The 5. Mann WR, Venkatraj VS, Allen RG, et al. Fanconi chest roentgenogram was normal. anemia: evidence for linkage heterogeneity on chroThe dyspnea improved with admosome 20q. Genomics 199]; 9: 329-37. Submitted March 11, 1991, and accepted in revised m i n i s t r a t i o n of oxygen at 3 L/minute, on which her arterial form April 16, 1991 P02 rose to 100 mm Hg. Sacral spine, lumbar spine, and limbs were tender to palpation. There APLASTIC CRISIS DUE TO was a grade 2/6 soft systolic murEXTENSIVE BONE MARROW mur along the left sternal border. NECROSIS AND HUMAN The liver and spleen were not enPARVOVIRUS INFECTION IN larged. The hemoglobin concenSICKLE CELL DISEASE tration was 1.6 g/dL with a mean corpuscular volume of 100 fL; the Aplastic crisis is a well-recog- reticulocyte count was 70.109/L, nized complication of sickle cell and the platelet count and white disease (SCD) defined by a tran- blood cell count were not signifisient arrest of erythropoiesis with cantly different from steadyrapidly worsening anemia. It is state values (Table I). The red usually associated with acute se- cell folate concentration was norlective erythroblastopenia, and mal. Numerous blood cultures human parvovirus B19 infection and urine culture remained sterJOHNSON M. LIU, M.D.

November 1991

Aplastic Crisis

Ten Days After Aplastic Crisis

Six Months After Aplastic Crisis

1.6 70 8.3 200

9.6 317 5.7 292

9,2 -8.9 286

ile. Results of plasmodium tests were negative. Hypercellular marrow was diagnosed from a bone marrow aspirate, and cultures of the aspirate were negative. A reticuloendothelial scan, performed with technetium-99m sulfur colloid and with indium chloride, showed a typical pattern of vaso-occlusive infarct with lack of marrow activity in a large area including the lumbar spine, sacrum, pelvis, entirety of both femurs, and humerus (Figure 1). A transfusion of 6 U of red blood cells brought her hemoglobin level to 9.6 g/dL (Table I). The patient's bone pain, dyspnea, and fever completely resolved within 2 weeks. Monthly transfusions were needed for 6 months because the pretransfusional hemoglobin level dropped below 7 g/dL with a HbS concentration below 20%, indicating low erythropoietic activity. Bone marrow biopsy was performed 6 months after the aplastic crisis and showed no abnormalities. Successive reticuloendothelial scans a f t e r 2 and 6 m o n t h s showed almost complete repopulation of the marrow. During the course of the anemia, serum IgM antibodies were present (optical density greater than 2; baseline value less than 0.2), but IgG antibodies against parvovirus antigens were undetectable (optical density less than 0.2) by capture r a d i o i m m u n o a s s a y [4]. Two months later, hematologic recovery coincided with the appear-

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BRIEFCLINICAL OBSERVATIONS

Figure 1. R e t i c u l o e n d o t h e l i a l scan obt a i n e d with l l l l n c h l o r i d e : t y p i c a l pattern of extensive vaso-occlusive infarct. T h e b o n e scan s h o w s t h e a b s e n c e o f marrow activity in a large area including the humerus, f e m u r , pelvis, and l o w e r spine.

ance of IgG (optical density: 1.8) and the decrease of IgM antibodies (optical density: 0.8). B19 parvoviremia, as assessed by the dotblot technique, was negative and

558

November 1991

viral DNA sequences were not detected using the polymerase chain reaction analysis. However, failure to detect virus was probably due to the late sampling. The earliest serum sample was taken more than 1 month after the beginning of symptoms. In SCD, vascular occlusion of small blood vessels can induce extensive bone marrow necrosis [5]. In the case herein described, this complication was probably the cause of a c u t e severe anemia rather than acute selective erythroblastopenia because bone marrow specimens did not show a relative decrease in erythroid precursors. T h e results of bone marrow aspirate analysis may be misleading due to sampling error for this diagnosis because only a small proportion of the marrow is analyzed. Radionucleotide scintigraphy is therefore the most sensitive method for the detection and delineation of bone marrow infarction [6]. Aplastic crisis due to extensive bone marrow necrosis in SCD has already been reported by Pardoll et al [2]. These authors postulated that viral infection could be associated with this complication. Conrad et al [3] then reported two similar cases with 8erologically documented human parvovirus B19 infection. Results of virus analysis in our case are in accordance with the cases described by Conrad et al [3] and confirm that bone marrow necrosis can complicate parvovirus infection. The pathophysiology of

The American Journal of Medicine Volume 91

this association remains uncertain. However, consistent with Conrad et al [3], we suggest that hypoxemia was probably caused by the effects of viral infection of the lungs. This may enhance severe sickling of red blood cells and thereby lead to bone marrow necrosis. Bone marrow necrosis caused directly by injury of the marrow progenitor stem cells or bone marrow stromal fibroblasts by human parvovirus B19 seems very unlikely. B. GODEAU,M.D. F. GALACTEROS,M.D. A. SCHAEFFER,M.D. H5pital Henri Mondor

Creteil, France F. MORINET, M.D.

H6pital Saint Louis Paris, France D. BACHIR, M.D. J. ROSA, M.D. J.L. PORTOS, M.D.

HOpital Henri Mondor Creteil, France 1. Serjeant GR, Topley JM, Mason K, eta/. Outbreak of aplastic crises in sickle cell anaemia associated with parvovirusqike agent. Lancet 1981; 2: 595-7. 2. Pardoll DM, Rodeheffer RJ, Smith RRL, Charache S. Aplastic crisis due to extensive bone marrow necrosis in sickle cell disease. Arch Intern Med 1982; 142: 2223-5. 3. Conrad ME, Studdard H, Anderson LJ. Aplastic crisis in sickle cell disorders: bone marrow necrosis and human parvovirus infection. Am J Med Sci 1988; 295: 212-5. 4. Modnet F, Courrouce AM, Galibert F, Perol Y. Development of an IgM antibody capture test using labeled fusion protein as antigen for diagnosis of B19 human parvovirus infection. J Virol Methods. In press. 5. Conrad ME, Carpenter JT. Bone marrow necrosis. Am J Hematol 1979; 7: 181-9. 6. Alavi A, Heyman S, Kim HC. Scintigraphic examination of bone marrow infarcts in sickle cell disorders. Semin Roentgenol 1987; 22: 213-24. Submitted January 15, 1991, and accepted in revised form May 28, 1991

Aplastic crisis due to extensive bone marrow necrosis and human parvovirus infection in sickle cell disease.

BRIEF CLINICAL OBSERVATIONS propriate bone marrow transplantation or treatment with immunosuppressive agents. Recognition of the heterogeneity of FA...
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