B19 Infection Research Articles

The Spectrum of Clinical Manifestations of Serious Human Parvovirus B19 Infection in Children without any Underlying DiseasesA Case Series

Human Parvovirus B19 causes mild to life-threatening illnesses, especially in immunosuppressed individuals. In the immunocompetent individuals, the severe spectrum of clinical manifestations of the virus infection is not widely known. This case series presents the spectrum of clinical manifestations of serious Parvovirus B19 infection in children without any chronic haematological or immunodeficiency disease. This series is about a total of 12 children who were positive for Parvovirus Immunoglobulin M (IgM) antibody and the age range was between 1-12 years. Fever, fatigue, and arthritis were the most common manifestations. Pure red cell aplasia, the specific manifestation of Parvovirus infection, was seen only in one-third of patients. All the children were treated with Intravenous Immunoglobulin (IVIG) along with supportive therapy. All except one had a successful recovery.

Pure Red Cell Aplasia Caused by Parvovirus B19 Infection in an Early Kidney Transplant Recipient

Pure Red Cell Aplasia Caused by Parvovirus B19 Infection in an Early Kidney Transplant Recipient

Parvovirus B19 infection in a patient of juvenile arthritis: A case report

Abstract Parvovirus B19 infection, or fifth disease or erythema infectiosum, is a self-limiting viral exanthem and can occur along with other connective tissue disorders. Occasionally, children may have preceding chronic joint complaints suggestive of juvenile idiopathic arthritis. A 7-year-old female patient presented to the outpatient department with a rash over her face, upper and lower limbs, and trunk, which was preceded by fever. The patient is a known case of juvenile arthritis. On examination, there were multiple erythematous and skin-colored plaques over cheeks; few pustules over lips; multiple erythematous papules over upper limbs, lower limbs, and trunk; multiple erythematous macules over palms; and swelling over interphalangeal joints of bilateral hands, elbow and knee joints with genu valgum deformity of limbs. The patient was given topical antibiotic and steroid combination cream and oral antihistaminic for her cutaneous complaints.

RELATIONSHIP BETWEEN PARVOVIRUS B19 AND OSTEOARTHRITIS: LITERATURE REVIEW.

Osteoarthritis and Parvovirus B19 infection present silent and gradual evolution, since the former is a degenerative process while the latter is often asymptomatic and may persist in the individual's body during their life. This study aims to analyze clinical studies that establish a correlation between degenerative osteoarthritis and Parvovirus B19 infection. Of the 62 studies found, 25 were chosen for reading in full. Analyzing only the studies that establish the correlation between the pathologies, seven confirm this relationship between Parvovirus B19 and Osteoarthritis, while one reports no relationship. No objective correlation could be found between the other articles studied. Our findings suggest that there is a close relationship between Parvovirus B19 and Osteoarthritis, with a higher prevalence of acquired causes, women and older adults, but it can manifest during life. However, it is essential to carry out new studies involving family history of patients with Osteoarthritis with positivity of Parvovirus B19, cohort studies between childhood and adult-old adult, so that it can elucidate this duality of congenital-acquired cause and, finally, raise treatment alternatives. Level of Evidence II, Systematic Review of Level II Studies.

Treating Parvovirus Triggered Refractory Hemolytic Anemia with Rituximab in Renal Transplant Recipients - A Report of Two Cases.

Parvovirus B19 is a small (26 nm), nonenveloped, single-stranded DNA (5.6-kb) virus. The only known host for parvovirus B19 is humans. Parvovirus B19 is directly cytotoxic to erythroid precursor cells of the colony- and burst-forming units. Human parvovirus B19 is the etiologic agent of erythema infectiosum and chronic pure red cell aplasia in immunocompromised individuals. Acute parvovirus B19 infection should be suspected in immunocompromised patients, who present with reticulocytopenic hemolytic anemia and thrombocytopenia. Intravenous immunoglobulin (IVIg) is the standard treatment for parvovirus-induced cytopenias. We report two cases of postrenal transplant who presented with reticulocytopenic anemia and were found to have parvovirus infection. They did not respond to conventional treatment with intravenous gamma globulin. Both patients were treated with rituximab with which they had improvement in clinical and hematological parameters. There was no previous documentation of using rituximab in the treatment of parvovirus-triggered autoimmune hemolytic anemia postrenal transplant patients. This article illustrates how rituximab will be helpful in this setting, of course, it is a new thought but requires further studies and validation.

Parvovirus B19 infection in children post hematopoietic stem- cell transplant: Clinical spectrum, management, and recommendations

Parvovirus B19 infection in children post hematopoietic stem- cell transplant: Clinical spectrum, management, and recommendations

Parvovirus B19'a Bağlı Akut Pleuro-Perikardit: 17 Yaşındaki Bir Erkek Çocuğun Olgu Sunumu

We report on a seventeen-year-old boy with acute pleuro-pericarditis with human parvovirus B19 (PVB19) infection. He presented with chest pain, fever and shortness of breath. On physical examination, he had orthopnea, increased temperature (38,4 °C), tachycardia and hepatomegaly. Echocardiography showed a pericardial effusion of 12 mm. Thoracic ultrasound revealed left pleural effusion of 10 mm. Serum anti-Parvovirus 19 IgM and Parvovirus B19 DNA were positive. Two weeks later; serum anti-Parvovirus B19 IgM was negative, pericardial effusion and pleural effusion were resolved. In our knowledge this case represents the first report of acute pleuro-pericarditis associated with Parvovirus B19 infection in a pediatric patient.

Molecular detection of human parvovirus B19 DNA amongst pregnant women attending antenatal clinic in Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria

Background: Parvovirus B19 infection causes a wide range of complication in pregnant women including spontaneous abortion, severe fetal anaemia, non-immune hydrops fetalis and even intrauterine fetal death, erythema infectiosum (5th) disease and aplastic crisis. Objective: To perform molecular detection of human Parvovirus B19 among pregnant women attending antenatal clinic in Nnamdi Azikiwe Teaching Hospital Nnewi, Anambra State, Nigeria. Materials and Methods: This is a cross-sectional study conducted among 92 consented pregnant women, between the ages of 20-40 years who are attending antenatal clinic in Nnamdi Azikiwe University Teaching Hospital Anambra State, Nigeria, from May 2020-November 2020. A total of 92 blood specimen was collected from the pregnant women. Result: Out of the 20 IgM positive samples analyzed for Parvovirus B19 DNA, 13(65.0%) had Parvovirus B19 DNA and 7(35.0%) were negative for Parvovirus B19 DNA. Prevalence of Parvovirus B19 DNA in relation to gestational age was highest (69.2%) among pregnant women who were in their 2nd trimester and the prevalence was lowest (0.0%) among pregnant women who were in their 3rd trimester. Prevalence of Parvovirus B19 in relation to history of blood transfusion was highest (100.0%) among pregnant women who have had transfusion history and the prevalence was lowest (0.0%) among pregnant women who had no transfusion history. Conclusion: The frequency rate of Parvovirus B19 DNA seropostivity was highest (65.0%) among the pregnant women investigated. The association of Parvovirus B19 DNA seroposivity with gestation age and history of blood transfusion was statistically significant.

Human parvovirus B19 infection in hospitalized patients suspected of infection with pathogenic microorganism.

Human parvovirus B19 (HPV B19) is a single-stranded DNA virus. The detection rate of HPV B19 in the blood of healthy blood donors using PCR technology was reported to be 6.323/100000. However, that among hospitalized patients suspected of being infected with a pathogenic microorganism is unknown. A retrospective analysis was conducted on 2,182 high-throughput NGS results for 1,484 inpatients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to October 2021 who were suspected of being infected with a pathogenic microorganism, as well as on clinical data of some HPV B19-positive patients. Human parvovirus B19 was detected in 39 samples from 33 patients. The positivity rate was 2.22% among patients and 1.78% among samples. HPV B19 was detected in 20 cerebrospinal fluid samples, 13 blood samples, 3 alveolar lavage fluid samples, 2 tissue samples, and 1 throat swab. Based on clinical symptoms and NGS results, 16 patients were diagnosed with HPV B19 infection. The number of HPV B19 sequences in these patients was greater than 6, and the patients showed common symptoms such as fever (14 cases), anemia (11 cases), and severe nervous system symptoms such as meningoencephalitis (9 cases) and Guillain-Barré syndrome with peripheral motor and sensory nerve axon damage (4 cases). All 16 patients had experienced events likely to lead to decreased immunity (11 had a history of trauma/surgery/major disease, 4 had a history of precursor infection, and 3 had used immunosuppressants) and 7 had a history of blood transfusion during hospitalization. After treatment with antiviral drugs (12 cases) and intravenous human immunoglobulin (3 cases), of the 16 patients, 14 patients improved. The HPV B19 infection rate in hospitalized patients suspected of microbial infection was 2.22%. Most patients with HPV B19 infection had a history of low immunity and blood transfusion. HPV B19 could be detected in various bodily fluids and tissues (especially cerebrospinal fluid) using NGS. Patients with severe HPV B19 infection may have nervous system damage such as Guillain-Barré syndrome and meningoencephalitis. Early diagnosis using NGS and treatment with antiviral drugs and immunoglobulin can improve prognosis.

An Overview of the Epidemiology, Pathogenesis, Diagnosis, and Treatment of Human Parvovirus B19

Human Parvovirus B19 (HPV-B19) infections are reported from different parts of the globe. The infection occurs in all age groups; however, most infections occur in childhood. There is evidence of exposure to the virus in about 80% of adults when screened for specific IgG. HPV-B19 is incriminated in several conditions like erythema infectious, aplastic crisis, hydrops fetalis and arthropathy. HPV-B19 is a cause of the Fifth disease (erythema infectious); it could also cause a febrile illness with or without rash in adults. Many adults especially women develop arthropathy and the condition could be chronic following a febrile illness. Patients (adults) with End Stage Renal Disease (ESRD) are prone to develop aplastic crisis or chronic anemia [1]. This review article aims to comprehensively describe the etiology, epidemiology, clinical features, diagnostic methods, and treatment in the management of HPV-B19.

Abstract 10031: Parvovirus Causing Severe Cardiogenic Shock With Recovery

Parvovirus B19 infection is common worldwide with the majority of people infected as young children. Its clinical presentation varies widely depending on the patient’s age and immune competence. Parvovirus B19 infection has been associated with myocarditis; however, its causal mechanism is unclear. A 57 year-old man who recently returned from Bolivia presented after five syncopal episodes. His initial troponin was elevated at 11.2 ng/mL. Electrocardiogram showed third degree heart block with a fascicular escape rhythm at 40 beats per minute. Echocardiogram revealed an ejection fraction of 45-50% and global hypokinesis of the left ventricle. Left heart catheterization showed mild non-obstructive coronary artery disease. His transvenous pacemaker was exchanged for a permanent pacemaker a few days later only to discover a repeat ejection fraction of 15-20%. The patient’s condition progressed to cardiogenic shock requiring inotropic and mechanical support. A comprehensive myocarditis workup was pursued which included a negative full respiratory viral panel, along with negative serum tests for coxsackievirus, hepatitis, human immunodeficiency virus, tuberculosis, syphilis, Lyme disease, strongyloidiasis and fungi. Urine toxicology prior to admission was negative for cocaine. Thyroid function tests were normal. Endomyocardial biopsy showed severe myocarditis with lymphocyte predominance. Staining was negative for fungi, spirochetes, Trypanosoma cruzi, herpes simplex virus, cytomegalovirus, or amyloid. There were no multinucleated giant cells seen on light microscopy. Subsequent PCR of DNA isolated from the biopsy specimen was positive for parvovirus (495 copies/100ng DNA) and Epstein-Barr virus (2046 IU/100ng DNA). His serum EBV viral load was undetectable. His parvovirus IgM level was negative and IgG level was positive. A diagnosis of fulminant parvovirus myocarditis was made. The patient was treated with steroids and five days of IVIG. Repeat echocardiogram showed recovery of his ejection fraction to 50-55%. Our case illustrates a complicated and rare case of fulminant parvovirus myocarditis in a previously healthy and active adult who luckily had recovery of his ejection fraction within 1 month.

Parvovirus-induced autoimmune hepatitis: First case in the literature

Parvovirus B19 infection is usually self-limiting in immunocompetent individuals. Twenty-five percent of infected individuals are
 completely asymptomatic during infection, with 50% of them presenting flu-like symptoms and the remaining patients presenting
 erythema infectiosum, arthralgia, or arthritis. More rarely, transient aplastic crisis is seen in individuals with chronic haemolytic
 disorders. Chronic pure red cell aplasia and aplastic anaemia may also be observed in immunocompromised patients. There is
 sufficient evidence in the literature suggesting that B19 infections can also cause a spectrum of liver diseases, ranging from elevated
 transaminase levels to acute hepatitis, fulminant liver failure, and even chronic hepatitis. This case report discusses a patient with
 acute parvovirus infection and newly diagnosed autoimmune hepatitis (AIH) and the role of this viral infection in the disease.

Case report: Unexpected parvovirus B19 infection in a myeloma patient treated with daratumumab

Multiple myeloma patients have an increased risk of infections due to both the inherent nature of the disease and ongoing treatment. We describe the case of a patient who was treated with daratumumab-lenalidomide-dexamethasone regimen for two years and developed a parvovirus B19 infection. The clinical picture, characterized by trilinear cytopenia, was initially attributed to anti-neoplastic treatment. Later on, when the patient’s condition worsened, an extensive diagnostic workup was applied and parvovirus B19 infection was detected by PCR. Due to the lack of effective antiviral drugs, the patient received IV immunoglobulins and it took 10 days to achieve a decrease in viral copies. Physicians should be aware that recent changes in the therapeutic scenario of multiple myeloma would make patients more susceptible to atypical infections in this patient setting.

Parvovirus В19 infection: lecture

Parvovirus B19 infection is best known as erythema infectiosum. However, infection with parvovirus B19 can lead to damage to various organs and systems, the development of severe complications up to death. The infection is most dangerous for people with immunodeficiency and hematological diseases. Serious consequences are possible with intrauterine infection of the fetus. Knowledge about the characteristics of the pathogen, the pathogenesis of the disease, the variety of clinical manifestations will allow the doctor to avoid diagnostic errors and provide the patient with timely medical care.

TWO CASE REPORT OF PARVOVIRUS B19 INFECTION IN HIV-INFECTED PATIENTS: DIFFERENT CLINICAL PRESENTATIONS FOLLOWING ACUTE AND PERSISTENT B19V INFECTION

Parvovirus B19 (B19V) infection could cause clinical manifestations depending on the host‘s immunologic and hematologic status. In immunocompetents individuals, clinical manifestations range from asymptomatic, or flu-like symptoms in childhood including a viral exanthem (fifth disease) to a fatal hydrops fetalis in pregnant women. B19V infect red blood cell (RBC) precursors and in immunocompromised hosts, such as HIV-infected patients, it could be manifested as pure red cell aplasia and chronic anemia. B19V may cause transient aplastic crisis (TAC) in patients with increased RBC destruction, including hereditary spherocytosis (HS). To report cases of B19V infection in HIV-positive adults in follow-up at Instituto Nacional de Infectologia Evandro Chagas. Case 1: A 27-year-old black male with HIV since childhood on irregular use of antiretroviral therapy (ART) complained of vertigo, headache, vomiting, fever. In April 2021 he had Hb 1,7 g/dL, Ht 6.5%, reticulocytes 0%, HIV viral load 40,305 cps/mL and CD4 + count 6 cells/μL. Up to October 2021 he required multiple RBC transfusions. Myelogram showed giants proerythroblasts with nuclear inclusions, B19V real time polymerase chain reaction (qPCR) detected 4.3 × 10 10 IU/mL, and B19V anti-IgM was negative. He received intravenous immunoglobulin (IVIG) and stabilized RBC counts. Nine months after treatment, he remained asymptomatic but had 11 cells/ μL CD4+ count and 27,642 HIV cps/mL due to poor adherence to ART. B19V was still detectable in qPCR (1.8 × 10 6 IU/mL), but he did not receive any additional treatment because blood counts were normal. Case 2: A 61-year-old white male with HIV since 2009 on regular use of ART, undetectable HIV viral load, but historically low CD4 + count, presented four weeks of lethargy, and an acute incident of dizziness, diarrhea, and syncope. He exhibited pancytopenia (Hb 5.6 g/dL, Ht 15.2%, WBC 1.48 × 10 9 /L, and platelets 41,000 per mm 3 ), non-immune hemolytic anemic features, jaundice, and palpable spleen. Reticulocyte counts were unavailable. He received transfusions of RBC, the HIV viral load at admission was undetectable, and CD4 + count 127 cells/ μL. The myelogram presented giant proerythroblasts with nuclear inclusions, and bone marrow had 95% cellularity and mild erythroid hyperplasia. B19V anti-IgM was indeterminate, while B19V qPCR detected 8.9 × 10 3 IU/mL, in August 2021. The patient received IVIG and nine months later, showed resolution of pancytopenia, but maintained elevated indirect bilirubin, indicative of chronic hemolysis. B19-DNA was no longer detected by qPCR, hematoscopy showed spherocytes, and the osmotic fragility test suggested RBC membranopathy, revealing an undiagnosed HS. Anemia is a common finding in the HIV setting, is often multifactorial, and represents a significant risk factor for mortality in AIDS. Our study highlights the importance of B19V infection be considered as a part of the differential diagnosis of anemia in this group. Clinicians should search for typical bone marrow and virologic findings. Identification of B19V DNA by qPCR was essential herein because of low sensitivity of serologic tests. Our findings showed that adherence to ART and the status of immunosuppression were crucial to the parvovirus clearance after IVIG. These cases highlight the challenging management of refractory parvovirus disease in immunosuppressed patient.

Use of oral fluid samples for the investigation of outbreaks of human parvovirus B19 infection.

The use of oral fluid (OF) samples for serological diagnosis of parvovirus B19 infection during outbreaks of erythema infectiosum had already been demonstrated, but the feasibility of using OF for the characterization of B19 genotypes circulating during outbreaks has not been described. The aim of this study was to assess the use of "in-house" PCR-based assays as a powerful tool for a rapid diagnosis and molecular characterization of B19 strains in OF samples during outbreaks. Paired serum and OF samples collected from anti-B19 IgM-positive patients, during two outbreaks of ertythema infectiosum (1999-2000 and 2004-2005), were tested by conventional (cPCR) and quantitative PCR (qPCR). qPCR was more sensitive than cPCR for detecting B19-DNA in both OF and serum. Overall, OF presented lower viral load (9.97 × 106 UI/mL) than serum (2.42 × 1010 UI/mL) and this difference was statistically significant. All OF samples obtained from patients in the age group < 14years presented low viral load (< 104IU/mL). No correlation was found between viral load and the number of days of onset of rash. Sequence analysis from PCR positive OF samples confirmed the circulation of subgenotype 1a (G1a) during these outbreaks. Our findings indicate that PCR-based assays may fail to detect B19-DNA in approximately 50% of OF compared to serum samples. Nevertheless, our study has shown for the first time that the genome sequence of the amplicon from non-invasive clinical sample is useful for molecular genotyping and may be a tool to clarify the genetic diversity of B19 strains circulating in distinct outbreaks.

Investigation of Parvovirus B19 in Hashimoto thyroiditis

Thyroiditis is a broad term that refers to a variety of clinical conditions marked by inflammation and damage to thyroid cells. These disorders could be caused by due to factors, including radiation, a microbial infection, or be linked to autoimmune thyroid disease, such as in Hashimoto thyroiditis (HT). This cross-sectional study aimed to the detection of anti-TPO antibodies and to investigate (Parvovirus B19) IgM and IgG antibodies in serum of patients to investigate their role in the pathogenesis of thyroiditis. The study included 91 patients suffering from thyroid dysfunction and diagnosed by performing of the thyroid hormone tests (FT3, FT4 and TSH) by Snibe Maglumi-800 Chemiluminescence Immunoassay, where they were divided into three groups namely (subclinical thyroiditis, hypothyroidism and hyperthyroidism). Then Moreover, the study investigates the determination which of them has HT by the detection of thyroid autoantibodies anti-TPO Ab and the detection of antibodies to specific (Parvovirus B19) IgM and IgG in the sera of patients by ELISA. The results of serology showed that the percentage of anti-TPO antibodies in the three investigated groups was (54.94%), and the highest percentage was in the hypothyroidism group, which amounted to (71.40%). The serological diagnosis also showed that the presence of antibodies to (Parvovirus B19) IgM was (90.10%) while, IgG levels were (100%) respectively. Conclusions: Parvovirus B19 infection is commonly seen in patients with thyroiditis.

Case Report: Susceptibility to viral infections and secondary hemophagocytic lymphohistiocytosis responsive to intravenous immunoglobulin as primary manifestations of adenosine deaminase 2 deficiency

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including systemic vasculitis, immunodeficiency, and cytopenia. We report a case of a 16-year-old girl affected by recurrent viral infections [including cytomegalovirus (CMV)-related hepatitis and measles vaccine virus-associated manifestations] and persistent inflammation, which occurred after Parvovirus infection and complicated by secondary hemophagocytic lymphohistiocytosis (HLH). HLH’s first episode presented at 6 years of age and was preceded by persistent fever and arthralgia with evidence of Parvovirus B19 infection. The episode responded to intravenous steroids but relapsed during steroids tapering. High-dose intravenous immunoglobulin (IVIG) helped manage her clinical symptoms and systemic inflammation. The frequency of IVIG administration and the dosage were progressively reduced. At the age of 9, she experienced varicella zoster virus (VZV) reactivation followed by the recurrence of the inflammatory phenotype complicated by HLH with neurological involvement. Again, high-dose steroids and monthly IVIG resulted in a quick response. Targeted next-generation sequencing (NGS) for autoinflammatory diseases and immunodeficiencies revealed the homozygous Leu183Pro ADA2 mutation, which was confirmed by Sanger analysis. ADA2 enzymatic test showed a complete loss of ADA2 activity. For about 3 years, IVIG alone was completely effective in preventing flares of inflammation and neurological manifestations. Anti-TNF treatment was started at the age of 13 for the appearance of recurrent genital ulcers, with a complete response. This case further expands the clinical spectrum of DADA2 and emphasizes the importance of extensive genetic testing in clinical phenotypes characterized by persistent unspecific inflammatory syndromes. The use of high doses of IVIG might represent a possible effective immune modulator, especially in combination with anti-TNF treatment.

Clinical utility of immune function based on IFN-γ monitoring of lymphocyte subsets for parvovirus B19 infection in renal recipients.

There should be a heightened index of suspicion for Parvovirus B19 (PVB19)-related anemia in organ transplant recipients. Thus far, there is no consensus or recommendation for clinical routine monitoring methods of PVB19 recipients to allow tailoring of immunosuppression. We conducted a retrospective study to evaluate the utility of the function (represented by the abilities to secrete IFN-γ) and numbers of lymphocyte subsets in monitoring PVB19 infections in renal recipients posttransplant. The enrolled 109 patients were split into 2 groups according to whether the recipients had an occurrence of PVB19 infection: 37 (33.94%) recipients developed PVB19 infection and 72 (66.06%) immune-stable recipients. The PVB19 infected group had significantly lower absolute counts and functions of different lymphocyte subsets compared with immune-stable recipients. We showed that the frequencies of IFN-γ+CD4+T cells, IFN-γ+CD8+T cells, and IFN-γ+NK cells increased markedly after treatment when compared to the occurrence in patients with timepoint before therapy, especially the percentages of IFN-γ+CD4+T cells were significantly higher. Receiver operating characteristic (ROC) analysis showed that the optimal infection indicator was IFN-γ+NK cells frequency, with an auROC curve of 0.925. Concomitantly, Cox regression analysis indicated that the post-therapy increasing level of IFN-γ secreting function was significantly predictive of recurrent infections (P<0.001). We recommend prospective risk stratification for the high-risk population at risk of early-onset PVB19 infection and its recurrence involves screening strategies of immune-based surveillance with the sensitive IFN-γ+secreting monitoring for antiviral prophylaxis and preemptive therapy goal. Clinical Trial Notation: clinical trial registration number: chiCTR-ROC-17010756.

Congenital hemolytic anemias due to erythrocyte membrane andenzyme defects

Erythrocyte membrane and enzyme defects are the most common cause of congenital hemolytic anemias in the Central European population. Diagnostics include erythrocyte morphology, special biochemical tests such as osmotic fragility (AGLT) and EMA. For enzymopenic hemolytic anemias, cost-effective biochemical analysis remains the gold standard, supplemented by molecular genetic diagnostics when appropriate. Therapeutically, near complete splenectomy reduces hemolysis significantly for spherocytosis. The residual spleen at least provides a considerable phagocytic function and better response to immunisation and by inference possibly better protection against severe post-splenectomy infection. For pyruvate kinase deficiency, which is not so rare, a new molecular therapy (Mitapivat) is currently being introduced. In G6PD deficiency, there are very few drugs that cause hemolytic crisis. Sudden onset of hemoglobinuria is an early important hallmark of severe hemolytic crisis in G6PD deficiency and these patients should be hospitalized. Aplastic crises in the setting of parvovirus B19 infection occur in all congenital hemolytic anemias. Transfusion is not preventable in most cases. Iron-excreting treatment is required in the rare patients in need of chronic transfusion.