Acute Human Parvovirus B19 Infection Triggers Immune-Mediated Transient Bone Marrow Failure Syndrome, Extreme Direct Hyperbilirubinemia and Acute Hepatitis in Patients With Hereditary Hemolytic Anemias: Multicenter Pathophysiological Study
试验速览
- 阶段
- 不适用
- 入组人数
- 244
- 试验地点
- 1
- 主要终点
- Number of cytopenias
研究概览
简要总结
Although many studies investigated the prevalence and manifestations of HPV-B19 infection in patients with sickle cell anemia (SCA), thalassemia, and hereditary spherocytosis (HS) separately, there is limited information about the extent to which HPV-B19 infection leads to severe complications and chronic infection.
详细描述
HPV-B19 is the smallest single-stranded, linear DNA virus that causes human diseases. Exposure to respiratory secretions is the most common means of transmission of this virus. Infection is associated with a variety of manifestations ranging from asymptomatic to severe complications that depending on the host's hematological and immunological status. No prospective comparative studies investigated the risks associated with this pathogenic virus and predicted the disease course and morbidity among hereditary hemolytic anemia (HHA) patients classified by their underlying diseases.
Nobody has studied the underlying causes of the different and unusual presentations in acute symptomatic HPV-B19 infection in hereditary hemolytic anemias patients. So that, this first head-to-head study to compare thalassemia, sickle cell anemia (SCA), and spherocytosis (HS) patients presented with acute symptomatic HPV-B19 infection.
Studying the relationship between viremia, humoral immune response, and the underlying disease in patients presenting with acute symptomatic HPV-B19 infection should be useful for clarifying the undiagnosed pathophysiological mechanisms and other accessory factors to improve the diagnosis and management.
Moreover, early diagnosis of risk factors of unusual presentations of acute symptomatic HPV-B19 infection will be a useful tool for better treatment strategy, follow up and prognosis as well as prevent future complications
Patients admitted from haematology clinics and emergency departments of Sohag and Assiut University Hospitals for HHA-related complications or manifestations suggesting HHA were screened continuously between February 2018 to February 2020 for enrolment in this study and monthly followed for at least one-year and 3 years post HPV-B19 infection.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed hereditary hemolytic anemias patients (age above 12 years) presented with signs and symptoms of hereditary hemolytic anemia (HHA) and admitted or treated in emergency departments or Hematology Units at Internal Medicine Departments of various university hospitals will be screened for enrollment in this study.
排除标准
- •• Patients will be diagnosed with non-HHA as ( autoimmune hemolytic anemia, microangiopathic hemolytic anemia (MAHA), Wilson disease, paroxysmal nocturnal hemoglobinuria (PNH).
- •HHA-patients will refuse to consent to this study.
- •Serologic evidence of recent virus infection other than human parvovirus B19 (HPV-B19); hepatitis A (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV,) cytomegalovirus (CMV), Epstein-Barr virus (EBV), or positive test for HIV.
- •HHA patients with uncontrolled diabetes mellitus (DM).
- •HHA patients with a history of nephrotic syndrome or chronic kidney disease(CKD).
- •HHA patients with a history of treatment by immunosuppressive drugs.
- •HHA patients with clinical and laboratory evidence of relevant toxicity related to iron chelation.
- •HHA patients with severe systemic diseases (such as cardiovascular, renal, and hepatic disease) or surgical/medical conditions that might interfere with follow-up instructions.
- •HHA patients with a life expectancy of less than 1 year.
- •HHA patients with psychiatric disorders or a history of drug abuse,
- •Pregnant women will be also excluded.
- •Patients are not a candidate for investigation (Refusal
结局指标
主要结局
Number of cytopenias
时间窗: 2 years
Complete blood count (CBC): peripheral blood samples will be withdrawn for diagnostic laboratory investigations and routine follow-up. 2- ml blood will be collected on potassium- ethylene diamine tetra-acetic acid (EDTA) anticoagulant coated tube for CBC using Cell-Dyn 3700, automated cell counter (Abbott diagnostic, Dallas, USA). The number of reticulocyte counts will be reported also.
Number of patients presenting with extreme hyperbilirubinemia during HPV-B19 infection
时间窗: 2 years
Measurement of direct and indirect bilirubin level which will be performed on Cobas c 311\& modular P auto analyzer (Roche diagnostics, Mannheim, Germany). Extreme hyperbilirubinemia will be considered when total bilirubin \>25 mg/dL.
Frequency of autoimmune bone marrow failure
时间窗: 2 years
The diagnosis of autoimmune bone marrow failure will be determined using several methods such as detection of 1. Several autoantibodies (antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA)), coombs test with pancytopenia and hypocellular bone marrow (BM) 2. Detection of the percentage of lymphocytes subsets, cytotoxic T cells and T helper cells, and regulatory T cells in the bone marrow by flowcytometry 3. Bone marrow aspiration if the patient had severe persistent cytopenia with histopathological studies of BM
Frequency of renal involvement and acute kidney injury
时间窗: Through study completion
The diagnosis of acute kidney injury (AKI) using AKI diagnosis last guidelines (Kidney Disease: Improving Global Outcomes KDIGO) and renal involvement will be determined by:- 1. Serum creatinine and blood urea 2. Urine amount and analysis 3. Albumin creatinine ratio 4. Histopathological studies of renal will be performed according to indication.
Number of hereditary hemolytic anemias (HHA) patients with symptomatic HPV-B19 infection
时间窗: 2 years
During the study period, any HHA-patient will have manifestations suggesting HPV-B19 infection (fever/ muscle pains /rash/ arthropathy/ lymphadenopathy/ rapid drop in (hemoglobin) Hb level and reticulocytopenia) and/or contact with a suspected case of erythema infectiosum will be investigated for anti-parvovirus B19 IgM and IgG immunoglobulin status. Those HPV-B19 seronegative will be retested 2 to 3 weeks later. HPV-B19 immunoglobulins (IgM and IgG) status will be determined by chemiluminiscent immunoassays (CLIA) technology from (Diasorin, Saluggia, Italy). The presence of signs, symptoms, HPV-B19 specific IgM, and absence of IgM of other viruses will be considered as a proof of recent symptomatic HPV-B19 infection. Patients will be divided based on previous criteria into two groups. Group I= HHA patients with acute symptomatic HPV-B19 infection, Group II= HHA patients without acute symptomatic HPV-B19 infection.
Common clinical manifestations of symptomatic HPV-B19 infection in patients with HHA
时间窗: 2 years
A questionnaire about the occurrence of. (Fever/ muscle pains /rash/ arthropathy / lymphadenopathy/ worsening of anemia/ Heart failure/ neuropathy) will be performed to determine the clinical manifestations of symptomatic HPV-B19 infection among patients with HHA.
Frequency of autoimmune hepatitis
时间窗: Through study completion
The diagnosis of autoimmune hepatitis (AIH) will be determined using AIH diagnosis last guidelines to diagnose and management of AIH in adults (.Revised Original Pretreatment Scoring System of the International Autoimmune Hepatitis Group) by:- 1. Detection of autoimmune hepatitis antibodies and immunoglobulin G level 2. Exclusion of other viral causes of hepatitis by serology and PCR of HAV, HBV, HCV, EBV, CMV 3. Exclusion of Wilson disease by serum ceruloplasmin, 24-hour urinary copper, 4. Exclusion of hemochromatosis by serum ferritin level 5. Histopathological studies of liver biopsies will be done after patients' acceptance in restricted conditions and according to guidelines for indication of biopsy.
次要结局
- Frequency of HPV-B19 reinfection during 3 years follow-up period and COVID-19 outbreak(3 years post HPV-B19 infection)
- Number of patients with HPV-B19 reinfection during short term follow-up period (one year)(1 year post HPV-B19 infection)
研究者
Mahmoud Ibrahim Yousef
Principal Investigator
Sohag University