CASE REPORT Year : 2021  |  Volume : 46  |  Issue : 3  |  Page : 192-194

Parvovirus-associated pure red cell aplasia − can we still make a diagnosis in resource-constrained setting by conventional laboratory method?

Sidra A Ali ACRF, MBBS, FCPS (Hem) 1, Muhammad S Shaikh2
1 Department, Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
2 Section of Hematology, Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan

Date of Submission16-Sep-2020Date of Acceptance23-Feb-2021Date of Web Publication13-May-2022

Correspondence Address:
Sidra A Ali
BBTs Spec Cert. (TSP) UK, Department, Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Acton, ACT 2601
Australia

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/ejh.ejh_39_20

Human parvovirus B19 has been linked with a wide variety of disorders in both pediatric and adult population. Commonly seen manifestation of the virus in patients with persistent infection of parvovirus B19 is suppression of erythropoiesis, leading to transient aplastic anemia and pure red cell aplasia. Host immunity plays an important role in disease expression, and the complications are generally reported in immunocompromised host or with underlying red cell disorders. We report a case of pure red cell aplasia in a previously healthy boy without any underlying disease, following asymptomatic infection with parvovirus B19. The diagnosis was based on clinical grounds with help of morphological findings typical of parvovirus B19 infection.

Keywords: parvovirus, pure red cell aplasia, transfusion

How to cite this article:
Ali SA, Shaikh MS. Parvovirus-associated pure red cell aplasia − can we still make a diagnosis in resource-constrained setting by conventional laboratory method?. Egypt J Haematol 2021;46:192-4
How to cite this URL:
Ali SA, Shaikh MS. Parvovirus-associated pure red cell aplasia − can we still make a diagnosis in resource-constrained setting by conventional laboratory method?. Egypt J Haematol [serial online] 2021 [cited 2022 May 14];46:192-4. Available from: http://www.ehj.eg.net/text.asp?2021/46/3/192/345244   Background 

Discovered in 1974, parvovirus B19 is the only member of the family Parvoviridae capable of causing disease in humans [1]. The infection is exceedingly common with incidence reaching up to 90% after sixth decade of life [2]. The virus is mainly transmitted via respiratory secretions, but transmission through transfusion of blood-derived products, vertically from mother to fetus and less commonly as nosocomial infection, are also reported in the literature [1],[3],[4],[5].

Disease spectrum of the virus is largely based on immune response of the host. The illness is usually subclinical and self-limiting. In most of the cases, no therapy is required as symptoms are mild and resolve within few days [6]. Common manifestation in an immunocompetent individual includes erythema infectiosum in children [7] and polyarthropathy syndrome [1] and various other inflammatory disorders in adults [8]. The virus may lead to fetal death in utero, hydrops fetalis, or development of congenital anemia owing to undeveloped immune system of the fetus [1]. In immunocompromised host, persistent B19 infection is usually manifested as pure red cell aplasia (PRCA) and chronic anemia [9].

Parvovirus B19 has a unique tropism for bone marrow and exclusively replicates in human erythroid progenitor cells [10]. This leads to suppression of erythrogenesis during infection and is more pronounced especially in patients with underlying hemolytic anemias like hereditary spherocytosis [11], hemoglobinopathies [12], and autoimmune hemolytic anemia [13].

Here, we describe a case of a young male child who presented with persistent anemia, and based on clinical and morphological features, suspicion of PRCA secondary to parvovirus infection was made.

  Case presentation 

A 20-month-old male child presented with complaint of progressive pallor for 1 year. His parents denied history of fever, cough, runny nose, night sweats, or rash. Mother reported uneventful pregnancy and normal delivery with no illness or hospitalization of the child in first few months of life. The patient was not on any medication. Over the course of 12 months, he had received multiple blood transfusions. On examination, the child was pale. There was no icterus, lymphadenopathy, or visceromegaly. Complete blood count showed hemoglobin 84 g/L, hematocrit 25.7%, mean corpuscular volume 81.8 fL, mean corpuscular hemoglobin 26.8 pg, total leukocyte count 8.6×109/L, and thrombocytes 170×109/L. Corrected reticulocyte count was found to be 0.05%. Peripheral blood smear showed normocytic and normochromic red blood cells with few reactive lymphocytes. No immature cells or blasts were noted. Other baseline investigations including coagulation studies, creatinine, and liver function tests were within normal limits.

As no plausible reason of pallor was identified, it was decided to proceed with bone marrow examination to establish the cause of anemia. Bone marrow aspirate was a cellular specimen with predominance of early proerythroblasts and paucity of mature erythroid precursors. These proerythroblasts had noticeable intranuclear inclusions as shown in [Figure 1]A. No ringed or nonringed sideroblasts were appreciated on Perls’ iron staining. Bone trephine also exhibited early proerythroblasts with relatively reduced intermediate and late normoblasts.

Figure 1 Bone marrow aspirate at 100x predominantly showing pronormoblasts with prominent intranuclear inclusions rejected to nuclear periphery (as shown by red arrows).

Click here to view

Based on isolated anemia with reticulocytopenia and paucity of mature erythroid precursors on bone marrow, clinical diagnosis of PRCA was made. Morphological findings of erythroblasts in the setting of PRCA were highly suggestive of infection with human parvovirus B19.

  Discussion 

PRCA, an uncommon red cells disorder characterized by maturation arrest of erythroblasts, is commonly caused by parvovirus B19 infection. Other viral infections like HIV, hepatitis, and drugs, especially anti-epileptics, also add to the list of causative agents [14].

Clinical suspicion is raised in patients with isolated normochromic normocytic anemia and reticulocytopenia having no obvious cause of low hemoglobin. Diagnosis of parvovirus infection is made serologically by detecting anti-parvovirus antibodies or by B19 DNA via PCR. Enzyme-linked immunoassay, radioimmunoassay, and immunofluorescence are few common techniques to detect anti-parvovirus B19 immunoglobulin M and immunoglobulin G antibodies. Together with difficulty in interpretation of results, lack of standardization between laboratories, and high rates of false-negative results, serological tests are not preferred in settings where molecular assays are available [15]. Careful interpretation of PCR is also required, as in contrast to high-level viremia in transient aplastic crises, low levels of B19 DNA are measurable for few months in serum after acute infection and for years in other tissues [16].

Albeit, bone marrow examination is not a part of diagnostic workup of parvovirus infection, morphological findings aid toward diagnosis especially in resource-constrained settings. There is predominance of giant proerythroblasts with a high nuclear to cytoplasmic ratio, thin rim of basophilic cytoplasm, and compact uncondensed nuclear chromatin [17],[18]. Multiple, distinct, large purple inclusions abutting nuclear margins are seen in the nuclei of few these cells [19]. Morphological findings are key to diagnosis in cases where serological and molecular tests are either inconclusive or are not available.

Persistent B19 infection producing PRCA has been reported in several patients with proven or suspected congenital immunodeficiency syndromes [9], but cases in immunocompetent hosts are also reported [20],[21],[22]. Our patient had no prodromal symptoms or underlying immunodeficiency. Unfortunately, both serological testing and molecular testing were not available in our institute to confirm the diagnosis. The patient also had financial constraints, so the sample could not be sent to reference laboratories.

Based on clinical suspicion and morphological findings the diagnosis of PRCA secondary to parvovirus B19 was made. The child received immunoglobulin and was discharged after full recovery. However, parents did not come for follow-up.

  Conclusion 

This case highlights the importance of careful microscopic examination as a diagnostic tool especially in developing countries where specific diagnostic facilities are not available and patients themselves have to bear the cost owing to unavailability of well-established health insurance system.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Heegaard ED, Brown KE. Human parvovirus B19. Clin Microbiol Rev 2002; 15:485–505.  
    2.Ke B. Parvovirus B19. In: Bennet JE DR, Blaser M, editors. Mandell, Douglas and Bennett’s principals and practice of infectious diseases. 8th ed. Philadelphia, PA: Churchill Livingstone Elsevier 2015. p. 1840–1847.  
    3.Evans JP, Rossiter MA, Kumaran TO, Marsh GW, Mortimer PP. Human parvovirus aplasia: case due to cross infection in a ward. BMJ 1984; 288:681.  
    4.Koziol DE, Kurtzman G, Ayub J, Young NS, Henderson DK. Nosocomial human parvovirus B19 infection: lack of transmission from a chronically infected patient to hospital staff. Infect Control Hosp Epidemiol 1992; 13:343–348.  
    5.Miyamoto K, Ogami M, Takahashi Y, Mori T, Akimoto S, Terashita Het al. Outbreak of human parvovirus B19 in hospital workers. J Hosp Infect 2000; 45:238–241.  
    6.Marano G, Vaglio S, Pupella S, Facco G, Calizzani G, Candura Fet al. Human parvovirus B19 and blood product safety: a tale of twenty years of improvements. Blood Transf 2015; 13:184–196.  
    7.Brass C, Elliott LM, Stevens DA. Academy rash. A probable epidemic of erythema infectiosum (‘fifth disease’). JAMA 1982; 248:568–572.  
    8.Adamson-Small LA, Ignatovich IV, Laemmerhirt MG, Hobbs JA. Persistent parvovirus B19 infection in non-erythroid tissues: possible role in the inflammatory and disease process. Virus Res 2014; 190:8–16.  
    9.Brown KE, Young NS. Parvoviruses and bone marrow failure. Stem Cells 1996; 14:151–163.  
    10.Pascutti MF, Erkelens MN, Nolte MA. Impact of viral infections on hematopoiesis: from beneficial to detrimental effects on bone marrow output. Front Immunol 2016; 7:364.  
    11.Kelleher JF, Luban NL, Mortimer PP, Kamimura T. Human serum ‘parvovirus’: a specific cause of aplastic crisis in children with hereditary spherocytosis. J Pediatr 1983; 102:720–722.  
    12.Brownell AI, McSwiggan DA, Cubitt WD, Anderson MJ. Aplastic and hypoplastic episodes in sickle cell disease and thalassaemia intermedia. J Clin Pathol 1986; 39:121–124.  
    13.Smith MA, Shah NS, Lobel JS. Parvovirus B19 infection associated with reticulocytopenia and chronic autoimmune hemolytic anemia. Am J Pediatr Hematol Oncol 1989; 11:167–169.  
    14.Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz JJ. Biology of erythropoiesis, erythroid differentiation, and maturation. Hematology: basic principles and practice. 6th ed. Philadelphia, PA: Churchill Livingstone; 2013.  
    15.Bredl S, Plentz A, Wenzel JJ, Pfister H, Most J, Modrow S. False-negative serology in patients with acute parvovirus B19 infection. J Clin Virol 2011; 51:115–120.  
    16.Soderlund-Venermo M, Hokynar K, Nieminen J, Rautakorpi H, Hedman K. Persistence of human parvovirus B19 in human tissues. Pathol Biol (Paris) 2002; 50:307–316.  
    17.Gupta D, Wu SL, Nguyen A. Human parvovirus B19 in the bone marrow with negative viral serologic results. Lab Med 2001; 32:8.  
    18.West NC, Meigh RE, Mackie M, Anderson MJ. Parvovirus infection associated with aplastic crisis in a patient with HEMPAS. J Clin Pathol 1986; 39:1019–1020.  
    19.American Society of Hematology. Erythroblasts with typical morphology of parvovirus B19 infection. ASH Image Bank, American Society of Hematology. 2014.  
    20.Lugassy G. Chronic pure red cell aplasia associated with parvovirus B19 infection in an immunocompetent patient. Am J Hematol 2002; 71:238–239.  
    21.Frickhofen N, Chen ZJ, Young NS, Cohen BJ, Heimpel H, Abkowitz JL. Parvovirus B19 as a cause of acquired chronic pure red cell aplasia. Br J Haematol 1994; 87:818–824.  
    22.Osaki M, Matsubara K, Iwasaki T, Kurata T, Nigami H, Harigaya Het al. Severe aplastic anemia associated with human parvovirus B19 infection in a patient without underlying disease. Ann Hematol 1999; 78:83–86.  
    
  [Figure 1]