Transient Red Cell Aplasia Research Articles

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Hypothesis: Low Vitamin A and D Levels Worsen Clinical Outcomes When Children with Sickle Cell Disease Encounter Parvovirus B19.

Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications.

Vitamin A and D Levels Correlate with Outcomes Following Acute Parvovirus B19 Infection in Children with Sickle Cell Disease

Background: Human parvovirus B19, a common childhood infection that typically causes mild disease in healthy individuals, causes life-threatening anemia due to transient red cell aplasia (aplastic crisis) in individuals with sickle cell disease (SCD). This complication often leads to hospitalization and red blood cell transfusions. Limiting the amount of transfusions is imperative to avoid alloimmunization. Strategies to mitigate complications from parvovirus B19 or reduce disease severity in SCD patients are needed. In this prospective observational study, we aim to describe the relationship between vitamin A and D levels and severity of symptoms during parvovirus B19 infection in pediatric patients with SCD.Methods: Twenty pediatric patients with SCD admitted to St. Jude Children's Research Hospital experiencing aplastic crisis and identified as having an active parvovirus B19 infection were under an IRB approved protocol (NCT02261480) and followed prospectively for 120 days post-infection. Acute parvovirus B19 infection was diagnosed by fever and a positive virus-specific IgM ELISA or PCR. Aplastic crisis was defined by worsened anemia without sufficient compensatory reticulocytosis in the setting of an acute parvovirus B19 infection. Virus-specific antibody responses were measured from sera or nasal washes (NW) by ELISA using parvovirus B19 virus-like particles (VLP) as target antigens. Peak serum antibody titers were defined (among measurements from Days 0, 7, 30, and 120). Total erythrocyte transfusion volumes required during the admission were quantified. Hematologic indices and vitamin A and D levels were obtained on Day 0. Vitamin A (retinol) was measured using UPLC and vitamin D (25[OH]D) was measured using a Roche Elecsys Vitamin D ELISA. Statistical analyses were performed with Spearman's rank correlation coefficient or Mann Whitney tests. We scored significance as p<0.05.Results: Twenty patients with different genotypes of SCD requiring hospital admission due to acute parvovirus B19 infection were sequentially enrolled (15 HbSS, 3 HbSC, 1 HbSD, 1 HbSβeta +thalassemia). Thirty-five percent (7/20) of patients were vitamin D deficient (VDD, defined here as <20 ng/mL) while 89% (17/19, one sample was not measured) of patients were marginally or severely vitamin A deficient (defined here as <20 μg/dL) on Day 0. Correlative analyses between vitamin levels and markers of disease severity are shown in figure 1. Lower vitamin D levels trended with lower hemoglobin (r=0.399, p=0.082) and there was a significant inverse correlation between transfused volume and vitamin D levels (r=-0.626, p=0.003, Figure 1B). There was a significant positive correlation of vitamin A levels on Day 0 with hemoglobin concentration (r=0.549, p=0.015, Figure 1D), and an inverse correlation between vitamin A levels and lactate dehydrogenase (r=-0.505, p=0.027, Figure 1F).Children with replete vitamin D levels exhibited significantly better peak virus-specific serum IgG (p=0.037) and IgA (p=0.011) responses (Figure 2A-B). Additionally, vitamin A, which plays an important role in mucosal immunity, correlated positively with virus-specific IgG (r=0.574, p=0.013) and IgA (r=0.480, p=0.044) in nasal passages on Day 30 (Figure 2C-D).Conclusions: In pediatric patients admitted to the hospital for acute parvovirus B19 infection, low vitamin A and D levels were associated with greater disease severity (greater hemolysis, lower hemoglobin concentration, and greater transfusion volumes). Higher vitamin levels were associated with better virus-specific antibody responses. While cause-effect relationships were not discerned in this study, we hypothesize that poor nutritional status contributed to poor outcomes and that efforts to improve nutrition may reduce the severity of parvovirus B19 disease in patients with SCD. [Display omitted] DisclosuresHankins: UpToDate: Consultancy; Vindico Medical Education: Consultancy; Global Blood Therapeutics: Consultancy; Bluebird Bio: Consultancy.

Autoimmune Liver Disease in Children with Sickle Cell Disease

To assess the incidence, clinical features, and outcome of autoimmune liver disease (AILD) in patients with sickle cell disease (SCD). Single center retrospective review of patients with SCD with AILD referred between 1999 and 2015. Thirteen of 77 (17%) patients with SCD with hepatic dysfunction were diagnosed with AILD (median age 11, range, 3.4-16 years) with a female preponderance (77%). Acute hepatitis and insidious onset were the commonest presentations. Two patients (15%) presented with acute liver failure. In 2 patients (15%), parvovirus B19-induced transient red cell aplasia preceded the diagnosis of AILD. All patients were positive for antinuclear and/or smooth muscle autoantibodies. Six of 12 patients (50%) had cholangiopathy on cholangiogram suggesting autoimmune sclerosing cholangitis (ASC). Liver biopsy, performed in 11 patients without complications, showed interface hepatitis in 90%. Patients with AILD were treated with standard immunosuppression. After a median follow-up of 3.8 years (range, 0.2-14.3), 10 patients are alive (1 was transplanted 6.4 years after diagnosis); 2 are lost to follow-up; 1 died of subdural hemorrhage before starting treatment for AILD. Five (42%) achieved full and 4 (33%) partial biochemical remission. Ulcerative colitis, present in 4 patients (2 male patients, 3 with ASC) was diagnosed in 2 patients before and in 2 patients after the diagnosis of AILD. AILD is not uncommon in patients with SCD, affecting mainly female patients and responding satisfactorily to immunosuppressive treatment. Liver biopsy is helpful in confirming the diagnosis and can be safely performed in the absence of acute vaso-occlusive sickling episodes. Ulcerative colitis is common in the presence of ASC.

Transient red cell aplasia in two brothers with sickle cell anemia and erythrovirus B19 infection.

B19V infection is associated with many clinical manifes-tations, depending on the immunological and hematologicalstatus of the patient. The virus has tropism for bone marrowerythroblasts, on which it exerts a cytotoxic effect and deter-mines temporary suspension of erythropoiesis, leading to atransient episode of red cell aplasia.

Transient erytroblastopenia of childhood: a review of 39 cases

Transient erythroblastopenia of childhood is an acute form of anemia characterized by a transient red blood cell aplasia, of unknown case, in the bone marrow. 39 patients were seen in our paediatric depatment during the period 2010 to 2013. The ages varied from 11 to 66 months. 26 patients had severe anemia, the lowest mean haemoglobin values being 52 (28-69) g/l. The reticulocyte count was low in 29 patients, whereas 10 patiants had reticulocytosis. No underlying haematologic diseases were found. All patients were tested for parvovirus B 19 infection, HHV-6, CMV, EBV, HHV-1,2 infections. No child showed B 19 DNA in serum or bone marrow collected at presentation. 19 patients showed HHV-6 (n = 11), CMV (n = 4), EBV (n = 2), HHV-1,2 (n = 1) DNA in serum or bone marrow collected at presentation. Apart from transfusion of red blood cell in 23 patients. Reticulocytosis, indicating beginning recovery, was observed after a mean interval of 10 days. All patients resolved within 3 weeks, without long-term sequale.

Coeliac disease presenting as osteoporosis and associated autoimmune thyroiditis and transient red cell aplasia

The Journal of the Ceylon College of Physicians (JCCP) is a peer-reviewed, open access journal published bi-annually by the Ceylon College of Physicians (CCP) in the last week of June and December.The objective of the Journal is to promote good clinical practice and influence policy making across the medical world through publication of original research and peer reviewed articles on current issues and to foster responsible and balanced debate on issues that affect medicine and health care in Sri Lanka. Contributions to the JCCP reflect its national and multidisciplinary readership and include current thinking across a range of medical specialties.

Keeping it in the family: Three relatives with HbSC disease and simultaneous acute pulmonary emboli

A 30-year-old African American female (Patient #1) with Hemoglobin SC (HbSC) disease presented with a 1 week history of progressive left flank and lower extremity pain with diffuse myalgias. She had a history of multiple prior vasoocclusive episodes requiring simple and exchange transfusions. At the time of admission on physical examination, she was afebrile and hemodynamically stable with an oxygen saturation of 100% in ambient air. The only pertinent finding was mild diffuse abdominal tenderness. Laboratory studies are summarized in Table 1 and were significant for leukocytosis with a left shift, anemia worse than baseline, a depressed reticulocyte count, a normal bilirubin but a mild elevation in transaminases. Chest radiography was normal. HbSC disease is a compound heterozygous condition characterized by inheritance of one gene for ‘‘S’’ hemoglobin (Glu-Val substitution in the 6th position of the b-globin chain) and one gene for ‘‘C’’ hemoglobin (Glu-Lys substitution in the 6th position of the b-globin chain), with subsequent formation of similar levels of HbS and HbC within the erythrocyte. HbCC disease is a non-sickling disorder which results in a mild hemolytic anemia. The combination of HbS and HbC is much more clinically significant suggesting that HbS has major disease modifying effect. Population studies suggest that while patients with HbSC have less frequent complications occurring later in life than those with HbSS disease, when complications occur they can be equally severe. In contrast, there is generally milder anemia and hemolytic complications, including aplastic episodes and cholelithiasis are less severe compared to HbSS disease [1]. In our first patient, the presence of diffuse pain was suggestive of a vasoocclusive episode (VOE). There were no abnormalities on history, physical exam, or chest radiography suggestive of acute chest syndrome (ACS). In terms of anemia, this patient was noted to have approximately a 3.5 g decrease in Hb concentration with an inappropriately low reticulocyte response. This suggested a VOE complicated by an aplastic crisis. Patient #1 was admitted to the medical service and commenced on treatment for a vasoocclusive epsiode with intravenous fluids and analgesics. She was commenced on low molecular weight heparin (LMWH) for deep venous thrombosis (DVT) prophylaxis. A red blood cell transfusion was administered for treatment of symptomatic anemia. The next day, the 24-year-old brother of Patient #1 (Patient #2), was admitted to the medical service. He also had HbSC disease and lived in same household as Patient #1. He had a history of cough productive of green sputum, fever, chills, myalgia and lower back pain for one week prior to admission. On physical examination, he was afebrile and had an oxygen saturation of 100% in ambient air. The rest of his exam was unremarkable other than pain with limb and spine motion. Laboratory studies are summarized in Table 1 and were significant for a leukocytosis with a left shift, worse anemia from baseline, an abnormally reduced reticulocyte response and mild hyperbilirubinemia. Chest radiography was normal. He was treated with intravenous fluids, analgesics and was administered LMWH for DVT prophylaxis. One of the recognized complications of sickle cell disease (SCD) is a reticulocytopenic anemia, referred to as an aplastic crisis or episode. This condition can be associated with a decrease in any peripheral blood cell lines, but most commonly, there are decreased mature erythrocytes and reticulocytes, and this is referred to as transient red cell aplasia (TRCA) [2]. A number of infectious agents have been implicated as either being causative or temporally related to such an episode. The best detailed of these is Parvovirus B19 (HPV B19), the causative agent of fifth disease. This virus is the only member of the Parvoviridae family known to be pathogenic in humans, occurring worldwide endemically [3]. Most infections occur in children and young adults and are highly contagious. The association between parvovirus infection and hypoplastic episodes in sickle cell anemia was first identified in 1981, when sera from 600 children in a London hospital were analyzed for HPV B19. Six children were identified with either the presence of the B19 antigen or its acute phase antibody [4]. All six were originally from Jamaica, had SCD with worsening anemia and evidence of bone marrow erythroid hypoplasia [4]. Other viruses recognized to be associated with red cell aplasia, although not specifically in SCD, include Epstein Barr, mumps, hepatitis, and Human Herpes virus 6 [5,6].

Acute human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of transient red cell aplasia (TRCA) and acute anaemia in patients with sickle cell disease (SCD). We report three cases of patients who developed nephrotic syndrome (NS) with chronic sequelae after initially presenting with HPV B19-associated TRCA. There was no correlation between evidence of HPV B19 infection and impaired renal function in our cohort of adult sickle cell patients. This is consistent with a view that although NS is potentially a rare complication of symptomatic acute HPV B19 infection, exposure to HPV B19 is not associated with an increased risk of renal disease.

Transient pure red blood cell aplasia as clinical presentation of congenital hemolytic anemia: a case report

Transient pure red blood cell aplasia as clinical presentation of congenital hemolytic anemia: a case report

Acute Human Parvovirus B19 Infection and Nephrotic Syndrome in Patients with Sickle Cell Disease

Human Parvovirus B19 (HPV B19) infection has previously been thought to be a trigger of nephrotic syndrome. The virus is associated with significant morbidity in patients with sickle cell disease (SCD) and a major cause of transient red cell aplasia (TRCA). We report three patients with SCD who presented with TRCA secondary to acute HPV B19 infection who subsequently developed significant proteinuria and nephrotic syndrome (NS) on outpatient follow up. There were 37 cases of acute HPV B19 infection in SCD patients admitted to King's College Hospital between November 2002 and July 2008. 29 cases were in children below the age of 16 years, eight in patients over the age of 16 years. The average age of the cohort was just over 11 years at diagnosis. Three patients developed NS within 4 months of acute HPV B19 infection and TRCA. Two of these patients were aged 17 and 26 years at diagnosis (patient 1 and 2 respectively), whereas the third was a child aged 11 (patient 3). Renal histology demonstrated the collapsing variant of focal segmental glomerulosclerosis (FSGS) in the acute phase of NS in patient 1, a characteristic finding associated with HPV B19-associated nephrotic syndrome. A subsequent biopsy in the same patient two years later demonstrated non-collapsing FSGS and marked interstitial fibrosis. Patient 2 had a renal biopsy performed 4 months after the onset of NS. This demonstrated non-collapsing FSGS, acute sickle nephropathy and significant chronic tubular atrophy. Patient 3 also had a renal biopsy 1 year after her acute HPV B19 infection which demonstrated the cellular variant of FSGS. Patient 1 was treated with immunosuppression and although the NS has improved slowly he continues to have significant proteinuria and progressive renal impairment. Patient 2 has not received immunosuppressive therapy and has also slowly improved from her NS but continues to have significant proteinuria; her estimated GFR has fallen from 169 ml/min to 104 ml/min six months after the acute HPV B19 infection. Patient 3 was treated with corticosteroids with subsequent improvement in serum albumin and symptoms but proteinuria persists with normal renal function. Consistent with previous reports, we observe that NS is a relatively rare complication of HPV B19 infection in young children with SCD (one case in 29 in our cohort). However, two out of eight patients older than 16 years developed this complication. Proteinuria in patients with SCD is common and gradual in onset, and eventually may progress to NS. Nephrotic syndrome of acute onset in adults with SCD is rare, only two cases were observed during a 6-year period among our cohort of over 400 adult patients with SCD. In both cases, they were associated with recent HPV B19 infection. It has previously been noted that acute HPV B19 infection in older patients with HbSC SCD have a more severe clinical course than younger children (Smith-Whitley et al., 2004). Our data, though limited by small numbers in the cohort, suggest that older SCD patients with acute HPV B19 infection may be more susceptible to chronic complications including the development of NS and progressive renal fibrosis. A correct diagnosis of the aetiology of NS is vitally important as the HPV B19-associated condition may not be responsive to corticosteroids, unlike other aetiologies of NS in this age group. It is possible that antiviral therapy may be of benefit in the acute setting but this needs further investigation. Furthermore, immunisation of older children and young adults who are HPV B19-naïve may be effective in preventing an important contributor of chronic renal disease in SCD patients.

A CHILD WITH HUMAN PARVOVIRUS B19 INFECTION INDUCED APLASTIC ANEMIA AND ACUTE HEPATITIS: Effectiveness of Immunosuppressive Therapy

Human parvovirus B19 (HPV B19) infections are usually asymptomatic or benign and self-limiting. In immunocompromised patients and patients with chronic hemolytic anemia, it can lead to transient red cell aplasia. Few reports in the literature have implicated HPV B19 as the possible cause of acute hepatitis and severe aplastic anemia in immunocompetent patients. Here, the authors report a previously healthy 6-year-old girl with acute hepatitis and severe aplastic anemia associated with HPV B19 infection diagnosed by serology (ELISA). Other common causes of these manifestations were ruled out. The clinical manifestations subsequently improved significantly with the use of immunosuppressive therapy confirming an autoimmune mechanism.

Transient parvovirus‐associated hypoplasia of multiple peripheral blood cell lines in children with chronic hemolytic anemia

Human parvovirus infection typically causes transient red blood cell aplasia. However, contrary to common perceptions, the hematopathologic effects of parvovirus infection are not always limited to the erythroid lineage. We describe here a consecutive series of 17 patients with chronic hemolytic anemia hospitalized for aplastic crisis, of whom 13 had transient hypoplasia of multiple peripheral blood cell lines.

Aplasia transitória da série vermelha na anemia falciforme

Sickle cell disease due to shortened life span of red blood cells by hemolysis, may present with severe anemia when erythropoietic suppression occurs due to infection by the Human parvovirus B19. The clinical presentation presents with fever, which may precede transient red cell aplasia, as well as laboratorial signs such as a drop in hemoglobin and significant reticulo cytopenia. Laboratorial diagnosis may be by immunofluorescence or enzymatic assays. Treatment is achieved by transfusion of packed red blood cells. Complications may be associated to this infection, including splenic and hepatic sequestration, acute chest syndrome, nephrotic syndrome, meningoencephalitis and strokes. Strategies of prevention are able to change the morbidity and mortality of this condition in sickle cell disease patients.

Transient red cell aplasia in siblings: a common environmental or a common hereditary factor?

During the years 1987-89, transient erythroblastopenia of childhood was diagnosed in 52 previously healthy Swedish children aged less than 4 y. Among these children there were four pairs of siblings, including one pair of identical female twins. This is a much higher familial occurrence than expected. The probability of finding 4 pairs of siblings with this disease in 50 families was estimated to be considerably less than 10–6. In the retrospectively analysed material, no environmental factor was implicated and no association with human leucocyte antigen could be proven. The twins demonstrated the disease simultaneously. Their anaemia was transient and did not recur, but showed certain features usually seen in congenital hypoplastic anaemia. The other pairs of siblings fulfilled the criteria for transient erythroblastopenia of childhood and several years elapsed between the development of the disease in siblings. Two of the fathers were reported to have had transient anaemia during their childhood. Our findings indicate that transient erythroblastopenia of childhood may involve hereditary factors, eventually demonstrating an autosomal dominant inheritance.

Life threatening parvovirus B19 and herpes simplex virus associated acute myocardial dysfunction in a child with homozygous sickle cell disease

Human parvovirus (HPV) B19, a common infection, frequently causes transient red cell aplasia in children with hemolytic anemia, such as sickle cell disease (SCD). It was considered to be a self-limited condition, easily treated with blood transfusion. However, acute splenic sequestration, acute chest syndrome, nephrotic syndrome, and stroke have been reported in SCD patients following HPV B19 infection. We report a 3-year-old child with SCD who developed fulminant myocarditis following HPV B19-related aplastic crisis. The diagnosis of myocarditis should be considered in a patient with hemolytic anemia with an infection with HPV B19 who develops signs of cardiopulmonary failure despite correction of anemia.

Epidemiology of human parvovirus B19 in children with sickle cell disease

AbstractHuman parvovirus (HPV) B19 causes significant morbidity and mortality in children with sickle cell disease (SCD), but little data are published about the epidemiology of HPV B19 infection and its associated complications in this patient population. In this study, prevalence and incidence rates of HPV B19 were determined in 633 patients with SCD followed at The Children’s Hospital of Philadelphia between November 1996 and December 2001. Thirty percent (30%) were HPV B19 immunoglobulin G (IgG) positive at first testing, and the 70% without evidence of past HPV B19 infection were tested annually. One hundred ten patients developed evidence of HPV B19 infection for an incidence rate of 11.3 per 100 patientyears. Sixty-eight episodes of HPV B19–induced transient red cell aplasia occurred with the following clinical events: fever (89.7%), pain (61.8%), acute splenic sequestration (19.1%), and acute chest syndrome (11.8%). Pain, fever, and acute splenic sequestration were more frequent events with acute HPV B19 infections compared with acute events in uninfected patients. The results of this epidemiologic study, the largest and most comprehensive to date, justify the development of HPV B19 prevention strategies to diminish the frequent and often severe complications associated with HPV B19 infections in patients with SCD.

Aplastic Crisis or Erythroid Hypoplasia in Sickle Cell Disease?

To the Editor.— A recent letter by Rosner1is critical of the use of the term "aplastic crisis" to describe the transient red cell aplasia occasionally observed in association with human parvovirus B19 infection2-5in children with sickle cell disease or other hereditary hemolytic anemias. Rosner contends that the phrase "aplastic crisis" is a misnomer because only "erythroid hypoplasia" occurs in this clinical entity. Whereas erythroid hypoplasia is the principal and most consistent hematologic manifestation in parvovirusinduced aplastic crisis, transient thrombocytopenia2-4and leukopenia3,4or neutropenia5occasionally have also been observed in association with aplastic crisis. Erythroid hypoplasia is also observed in other disease states with transient or chronic bone marrow failure, eg, in aplastic anemia or in transient erythroblastopenia of childhood. The exclusive use of the term "erythroid hypoplasia" in place of "aplastic crisis" to describe the clinical entity of transient parvovirus-induced bone marrow aplasia

Transient red blood cell aplasia in association with viral hepatitis. Occurrence four years apart in siblings

Transient red blood cell aplasia in association with viral hepatitis. Occurrence four years apart in siblings