Transient Red Cell Aplasia Following Acute Human Parvovirus B19 Infection in a Sickle Cell Disease Patient in Aplastic Crisis
Osho Poα, Joseph Aaσ, Ojo Maρ, Odunlade OcѠ, Osho Es¥, Okunnuga Na§ & Oni Oiχ
Parvovirus B19 (PVB19) is a DNA virus, non-enveloped, with icosahedral nucleocapsid symmetry and measures 22-24 nm in diameter. Transmission is via blood transfusion being one of the transfusion transmissible viruses though infection can occur spontaneously. It is a major disease patients and Thalassemia patients, with clinical manifestation ranging from asymptoma- tic disease in immunocompetent to symptomatic disease in the immunocompromised. At risk group include children, pregnant women, immunocompromised and those with chronic haemolytic anemia. Clinical features include erythema infectiosum (fifth disease) in children,
arthropathy, aplastic anemia/crisis and fetal hydrops.
Acute parvovirus B19 infection can be diagnosed by demonstrating the presence of HPV B19 IgM, with or without positive IgG using enzyme immunoassays (EIAs). Evidence of past infection is the presence of HPVB19 IgG. Red cell aplasia can be defined as a fall in haemoglobin concentration to below steady‐state levels of more than 30g/l associated with a very low reticulocyte count.
This was a case report of a 15 year old girl, a known sickle cell anemia patient (HbSS) diagnosed a year after birth and has been stable on folic acid. Routine follow-up clinic visit has been irregular as patient had been clinically stable and crisis free on till about 15 months prior to presentation at our centre. Her steady state PCV hence could not be ascertained. She however started having extreme fatigue, tiredness and easy fatigability about 15months prior to her referral to our centre. On examination she was found to be severely pale with PCV of 6%. This necessitated her been transfused with whole blood at the peripheral health centre where she was been managed. PCV improves post transfusion for a few days after which the patient starts having dark coloured urine, jaundice, bone pains and generalized body pains. subsequently, the PCV drops to pre-transfusion level or below necessitating her frequent transfusion, atleast twice a month for upto 8 months before her referral to a tertiary health centre for further investigation.
Investigations done include CBC, PBF, BMA, repeat haemoglobin genotyping using HPLC G6PD assay and Human Parvovirus B19 screening. Findings were in concordance with aplastic anaemia, negative for G6PD deficiency but was positive on screening for HPVB19 with a high persistent fetal hemoglobin of upto 31%.
Author α ρ: Department of Haematology, Faculty of Basic Clinical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria.
σ: Department of Microbial Pathology, Faculty of Basic Clinical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria.
Ѡ: Department of Paediatrics, Faculty of Clinical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria.
¥ §: Department of Radiology, Trauma Surgical Centre and University of Medical Sciences, Ondo City, Ondo State, Nigeria.
χ: Department of Haematology/virology, University of Medical Sciences Teaching Hospital, Akure.
Parvovirus B19 (PVB19) is a DNA virus belonging to the parvoviridae family and of the erythrovirus genus (1). Alongside hepatitis B virus (HBV), hepatitis C virus (HCV), human immunode- ficiency virus (HIV), human T cell leukaemia virus I (HTLV1), cytomegalovirus (CMV) and Epstein -Barr virus (EBV), It is another transfusion transmissible viruses. It is non-enveloped, with icosahedral nucleocapsid symmetry, and measu- res 22-24 nm in diameter. The virus has a linear nucleic acid (DNA) of ~5.6 kb in length with three (3) genotypes 1, 2 and 3. Genotype 1 had been implicated for the majority of human infections worldwide while genotypes 2 and 3 appear to have some geographic and temporal variation in distribution. The strength of them virus is seen in its resistant to dry heat, freezing and lipid solvents but can be inactivated by formalin, β-propiolac tone and gamma irradiation (2).
The main transmission route of the virus is as droplet infections, vertically through placental to fetus and through blood transfusion. The population at risk include children, pregnant women, immunocompromised and those with chronic haemolytic anemia such sickle cell and Thalassemia patients (1,3), with clinical manifestation ranging from asymptomatic disease in immunocompetent to symptomatic disease in the immunocompromised. Clinical features include erythema infectiosum (fifth disease) in children, arthropathy, aplastic anemia/crisis and fetal hydrops (2).
Acute infection is associated with a viremic phase shortly followed by IgM antibody production (10–14 days post-infection). This is followed by IgG antibody production against the viral capsid. Viraemia declines with IgM production; IgM declines after a few months but IgG persists longer to convey immunity against reinfection. Infrequently, low level PVB19 nucleic acid may persist with IgG for months or years (2).
Parvovirus B19 infections has been reported globally and are evident with the secretion of immunoglobulin M (IgM) antibodies in plasma while IgG signify previous exposure. The clinical manifestation varies widely depending on the immunological and haematological status of the host as the virus has a direct cytopathic effect on erythroid progenitors in bone marrow leading to an arrest in the maturation and subsequent anaemia. According to Serjeant et al., individuals with underlying haemolytic disorders, such as patients with sickle cell anaemia (SCA), PVB19 infection may cause transient erythroblastopenia (TEB), characterized by a fall in haemoglobin level with reticulocytopenia (4). Other manifestations of parvovirus infection include arthritis, vasculitis, myocarditis, liver failure and fetal loss (2). SCA patients have accelerated premature haemolysis with significant reduction in red cell half life (5). Generally, the chronic haemolysis and resulting anaemia is well tolerated however, a reduction in the level of haemoglobin below the steady state may be detrimental to the patient; necessitating blood transfusion (6, 7).
Transfusion predisposes SCA patients to increased risk of immunological and infectious complications and accurate epidemiologic data on the frequency of Parvovirus B19 infection in patient with sickle cell anaemia are essential for assessing the potential effect of viral prevention programs in this patient population (8). Though the findings from the work of Iheanacho et al. (2014) suggests that it may not be cost effective to recommend routine donor screening for PVB19 antibodies. However, because of the increased risk of aplastic crisis in SCA patients, SCA patients who require transfusion and are seronegative for PVB19 should have the blood screened for PBV virus. We hereby present a case of a 13 year old sickle cell anaemic girl with PVB19.
Patient was a 15‐year‐old female with HbSS and infrequent admissions and had never received any previous blood transfusions prior to this episode of ill health as she has been clinically stable on folic acid. her steady‐state PCV could not be ascertained due to irregular follow-up clinic visit. In February 2019, she presented with lethargy, easy fatigability and dyspnoea. she was extremely pale with a PCV of 6%. She was managed supportively with blood transfusion. complete blood count following transfusion showed the following: PCV (28.1%), Haemoglobin (10.0g/dL), white blood cell (1,200/cmm3), platelets (59,000/cmm3), lymphocyte (59.6%), neutrophils (35.3%), Baso, Eos, Monocytes (5.1%), Red blood cell (3.53 *1012/L), MCV (79.8fL), MCH (28.3Pg), MCHC (35.5g/L) and PCT (0.04%). Few weeks post transfusion, she presented at the private health facility where she is being managed with extreme weakness, passage of dark coloured urine, jaundice and generalized body pains. Her complete blood count showed PCV (9.1%), Haemoglobin (2.9g/dL), white blood cell (1,600/cmm3), platelets (60,000/cmm3), lymphocyte (68.9%), neutrophils (27.2%), Baso, Eos, Monocytes (3.9%), Red blood call (0.92 *1012/L), MCV (99.0fL), MCH (31.5Pg), MCHC (31.8g/L) and PCT (0.06%). She was transfused with 2 units of whole blood on account of this. The cycle of low PCV, blood transfusion, relapse of anaemic crisis continued, necessitating her being transfused at least once every month for upto 8 months before her referral to a tertiary health Centre for further management.
At admission, her haemoglobin genotyping was repeated using HPLC revealed a foetal hemoglobin (31.8), haemoglobin A0 (26.4), haemoglobin A2 (1.6), haemoglobin S (40.2). Further investigations carried out include Complete Blood Count with Peripheral Blood Film which revealed pancytopenia. Bone Marrow Aspirate and cytology was also done which showed hypocellular marrow. Other tests carried out include G6PD assay which was within reference range of activity (247 mU/109 erythrocyte), as well as Human Parvovirus B19 screening which was positive for HPV B19 DNA in blood using Parvo virus B19 DNA test.
Patient was managed conservatively with methy- lprednisolone (32mg/dl), cyclophosphamide (100 mg/dl) and immune boosters such as glutathione supplementation and selenium-based therapy.
OUTCOME AND FOLLOW-UP
Patient recovered from acute haemolytic episode with remarkable increase in PCV and a reduction in the frequency of transfusion. She was transfused once in the last four months and has returned back to school and normal activity, maintained on the present line of supportive care.
Parvovirus B19 is one of the emerging transfusion transmissible infections. Interventions for parvovirus B19 infection need to balance the low risk of infection at a population level with the potential for serious adverse outcome for particular groups, notably the fetus, people with haemoglobinopathies and the immunocompromi- sed. The virus is stable in heat and remains infective even after treatment with dry heat at 80°C for 72 hours, which was used for treating some blood products (9, 10). It has been widely studied in various countries among healthy blood donors and sickle cell patients with results indicating a high seroprevalence of the virus in the study areas however there are limited publications on parvovirus in SCA patients and blood donors in our environment. Iheanacho (2013) reported a seroprevalence rate of 66% for IgG antibody in Nigerian healthy blood donors (2). Abraham et al and Munoz et al reported seroprevalence of 65% each for IgG antibody in blood donors in India (11) and Salamanca, Spain (12) respectively. In various studies in developed nations, rates between 55 – 77% were reported (13–15). In non-immune sickle cell anaemia patients, the clinical manifestation of the virus upon infection may include transient aplastic crisis, which is indicated by a fall in haemoglobin with reticulocytopenia. Serjeant et al in their study of epidemiology of human parvovirus B19 infection in Jamaica in homozygous sickle cell disease found that PVB19 infection accounts for most if not all aplastic crisis in SS disease (4). The reticulocyte percentages of IgG antibody positive SCA patients are generally higher than that of IgM positive SCA subjects. This affirms the risk of transient aplasia associated with acute or persistent parvovirus infection documented in some previous studies (16). A high seroprevalence of IgG anti-PVB19 antibodies in sickle cell patients and voluntary blood donors in our environment had been reported. This suggests that it may not be cost effective to recommend routine donor screening for PVB19 antibodies. However, because of the increased risk of aplastic crisis in SCA patients, SCA patients who require transfusion and are seronegative for PVB19 should have the blood screened for PBV virus.
The high seroprevalence of IgG anti-PVB19 antibodies in sickle cell patients and voluntary blood donors in our environment suggests that it may not be cost effective to recommend routine donor screening for PVB19 antibodies. However, because of the increased risk of aplastic crisis in SCA patients, and severe complications which may occur following the infection such as nephrotic syndrome and progressive renal fibrosis, SCA patients who require transfusion and are seronegative for PVB19 should have the blood to be transfused screened for Parvovirus B19. The discovery of this case hereby calls for intentional approach to parvo-virus B19 (2). Severe complications associated with acute HPV B19 infections in patients with SCD supports the development of HPV B19 prevention strategies, targeting particularly patients who are still HPV B19‐naïve.
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