Relação entre a infecção por Helicobacter pylori e doenças hematológicas: uma revisão integrativa / The relationship between Helicobacter pylori infection and hematologic diseases: an integrative review

Helicobacter pylori, uma bactéria gram-negativa, desde 1984 vem sendo associada às doenças gástricas. A partir da década de 1990, surgiram crescentes relatos indicando a relação da infecção com manifestações extragástricas. Nesse sentido, o objetivo do estudo foi investigar, através de uma revisão integrativa, as evidências relacionadas à H. pylori e a presença de doenças hematológicas, focando na anemia por deficiência de ferro (ADF) e na púrpura trombocitopênica idiopática (PTI). Bases de dados foram consultadas com as palavras-chave e descritores Helicobacter pylori, Doenças extragástricas, Doenças hematológicas, Anemia ferropriva e Púrpura Trombocitopênica Idiopática, nos idiomas inglês, português e espanhol, combinados com o operador booleano "AND". Após a leitura de 1.964 títulos, 85 artigos atendiam aos critérios de inclusão. Com a exclusão dos artigos duplicados e pela análise dos resumos, 62 trabalhos foram selecionados e lidos na íntegra. Por fim, 27 estudos foram incluídos: 13 relacionados à ADF e 77% deles encontraram associação com H. pylori, e 14 relacionados à PTI, nos quais a relação com a bactéria foi encontrada em 93%. As evidências que associam essas doenças hematológicas com H. pylori são expressivas, portanto, mais estudos são necessários para elucidar os mecanismos relacionados e contribuir para prevenção, diagnóstico e tratamento mais eficazes.

Helicobacter pylori is a gram-negative bacterium that has been associated with gastric diseases since 1984. Since the 1990s, there have been increasing reports indicating that the infection may also be associated with extragastric manifestations. This integrative review aimed to investigate the evidence on the relationship between H. pylori and hematological diseases, specifically iron deficiency anemia (IDA) and idiopathic thrombocytopenic purpura (ITP). Databases were searched for the keywords "Helicobacter pylori," "extragastric diseases," "hematologic diseases," "iron deficiency anemia," and "idiopathic thrombocytopenic purpura" in English, Portuguese, and Spanish, combined with the boolean operator "AND." The search yielded 1,964 studies. After reading the titles, only 85 met the inclusion criteria. Sixty-two studies were selected for full-text reading after exclusion of duplicates and abstract analysis. Finally, 27 studies were included in this review. Thirteen studies addressed IDA, among which 77% found an association with H. pylori; whereas 14 studies addressed ITP, among which 93% found a relationship with H. pylori. There is strong evidence supporting the association between hematologic diseases and H. pylori. Further studies are needed to elucidate the mechanisms involved in this relationship, contributing to more effective prevention, diagnosis, and treatment.

Maternal anemia and preterm birth among women living with HIV in the United States.

BACKGROUND: Women living with HIV (WLHIV) have a higher prevalence of anemia than women without HIV, possibly related to the effects of HIV and antiretroviral medications. OBJECTIVES: To estimate the prevalence of anemia in the third trimester of pregnancy and the effect of anemia on preterm births in WLHIV in the longitudinal, US-based Pediatric HIV/AIDS Cohort Study (PHACS). METHODS: During the third trimester, we obtained up to three 24-hour dietary recalls to estimate daily intakes of nutrients and measured serum concentrations of iron, vitamin B6, vitamin B12, zinc, folate, ferritin, total iron-binding capacity (TIBC), and high sensitivity C-reactive protein. Third trimester anemia was defined as hemoglobin < 11 g/d and iron-deficiency anemia (IDA) was defined as low ferritin, high TIBC, and low transferrin saturation. A preterm birth was defined as birth at < 37 completed weeks of gestation, regardless of etiology. We fit separate modified Poisson regression models for each outcome (anemia, preterm birth) and each main exposure, adjusted for confounders, and report adjusted prevalence ratios (aPR) and 95% CIs. RESULTS: Of the 267 WLHIV, 50% were anemic in the third trimester, of whom 43.5% (n = 57/131) had IDA. On average, women with anemia were younger, were more likely to be black, started antiretroviral medications in the second trimester, had a low CD4 count (<200 cells/mm3) early in pregnancy, and were less likely to meet recommended intakes for iron, B6, and folate. The prevalence of anemia was greater in WLHIV with a low CD4 count (aPR = 1.65; 95% CI: 1.20-2.27) and high HIV viral load (>10,000 copies/mL; aPR = 1.38; 95% CI: 1.02-1.87). In total, 16% of women delivered preterm. Anemia was associated with a 2-fold (aPR = 2.04; 95% CI: 1.12-3.71) higher prevalence of preterm births. CONCLUSIONS: Anemia is common in pregnant WLHIV, highlighting the need to address the underlying factors and clinical outcomes of anemia in this population.

Adherence in a pragmatic randomized controlled trial on prophylactic iron supplementation during pregnancy in Maputo, Mozambique.

OBJECTIVE: Assessing the level of adherence and its determinants is important in appraising the overall effectiveness of trials. The present study aimed to evaluate the extent of adherence and its determinants in a pragmatic randomized controlled trial of Fe prophylaxis during pregnancy in Maputo, Mozambique. DESIGN: A pragmatic randomized controlled trial. SETTING: Two health centres (1° de Maio and Machava) in Maputo, Mozambique. SUBJECTS: Pregnant women (≥12 weeks' gestation, ≥18 years old, non-high-risk pregnancy; n 4326) attending prenatal care consultations at two health centres were randomized to receive routine Fe (n 2184; 60 mg ferrous sulfate plus 400 µg folic acid daily throughout pregnancy) or selective Fe (n 2142; screening and treatment for anaemia and daily intake of 1 mg folic acid). RESULTS: The level of adherence was 79% for having two or more visits, 53% for adequate prenatal care and 67% for complete intake of Fe/folic acid tablets during the trial. The correlation between the adherence measures ranged between 0·151 and 0·739. Adherence did not differ by trial arm, but there were centre differences in adequate prenatal visits and intake of tablets. Older women (>20 years) and those with a history of abortion were more likely to achieve greater adherence, whereas an increased number of previous births decreased the likelihood of adherence. HIV positivity decreased the likelihood of adherence in one trial centre and increased it in the other. CONCLUSIONS: The variation in adherence by trial centre, women's characteristics and outcome measures suggests that adherence in trials fully depends on participants' behaviour and can be increased by paying attention to contextual factors.

Positive relationship between a polymorphism in Helicobacter pylori neutrophil-activating protein a gene and iron-deficiency anemia.

BACKGROUND: Numerous studies have suggested a link between iron-deficiency anemia (IDA) and Helicobacter pylori infection. Previously, we found that strains isolated from IDA patients showed higher levels of Fe ion uptake and Fe-ion-dependent rapid proliferation than those of strains derived from patients without IDA. MATERIALS AND METHODS: Twenty-four H. pylori strains from IDA patients (IDA strains) and 25 strains from patients who had H. pylori gastritis without anemia (non-IDA strains) were examined. Their nucleotide sequences of napA, fur, and feoB, which contribute to Fe ion uptake, were determined. RESULTS: Numerous polymorphisms of the three genes were found in both strains. Frequency of neutrophil-activating protein A (NapA), which encoded by napA, with threonine at amino acid residue No. 70 (Thr70-type NapA) was significantly higher in IDA strains than in non-IDA strains. Strains with Thr70-type NapA showed significantly higher levels of Fe(3+) and Fe(2+) uptake than did strains with other types, Ser70-type of NapA, which is found in standard strains. Other significantly different occurrences of polymorphisms between IDA and non-IDA groups were not observed in these genes. CONCLUSION: The results suggest that H. pylori strains with Thr70-type NapA have enhanced Fe ion uptake ability and are associated with the pathogenesis of IDA.

Iron deficiency in children with HIV-associated anaemia: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to determine the prevalence of iron deficiency in HIV-infected children from high- and low-income settings and compared it with that of HIV-uninfected controls. We searched five major databases for primary studies reporting on anaemia and iron markers in HIV-infected children. A pooled analysis was done using random-effects models, with Forest plots and heterogeneity test estimates provided. Fifteen articles (2778 children) met the inclusion criteria. In the pooled analysis, mean overall prevalence of iron deficiency in HIV-infected children was 34% (95%CI 19-50%). Prevalence rates were similar in high-income (31%; 95%CI 2-61%) and low-income settings (36%; 95%CI 17-54%) (p=0.14). Studies that included a HIV-uninfected control population (n=4) were only available from low-income settings and showed less iron deficiency in HIV-infected children (28%) than in HIV-uninfected children (43%); OR 0.50 (0.27-0.94); p=0.03. The findings suggest that HIV-infected children are less likely to be iron deficient when compared with HIV-uninfected children. Possible explanations for this include HIV-induced haematosuppression and associated hypoferraemia, with adequate iron stores. Nevertheless iron deficiency is a common co-morbidity in HIV. Studies are needed to determine the role of iron deficiency in HIV-associated anaemia and the effects of iron supplementation in this population.

Human herpesvirus 6 in hematologic diseases in China.

BACKGROUND AND OBJECTIVE: The prevalence and pathogenic role of human herpesvirus 6 (HHV-6) in various benign and malignant hematologic diseases remain largely unknown. The aim of this study was to search for a possible involvement of HHV-6 in the pathogenesis of hematologic diseases. DESIGN AND METHODS: The presence of HHV-6 DNA sequences was examined by polymerase chain reaction (PCR) in bone marrow mononuclear cells from 241 patients with benign and malignant hematologic diseases in China. Platelet-associated immunoglobulin (PAIg) of 66 idiopathic thrombocytopenic purpura (ITP) patients was measured by competitive enzyme-linked immunosorbent assay. The presence of HHV-6 DNA in sera from 31 ITP patients was examined by PCR. Paired serum samples from 19 ITP patients were analyzed for anti-HHV-6 IgG titers using an indirect immunofluorescence assay. RESULTS: HHV-6 DNA was detected in 41% and 37.5% of ITP and acute leukemia patients respectively, but in only 6.7% of patients with iron deficiency anemia. HHV-6 positivity for ITP patients with excessive PAIgG was significantly higher than in patients with a normal level of PAIgG. HHV-6 DNA was not detected in any of the serum samples from ITP patients. None of the 19 cases of ITP showed a significant increase in anti-HHV-6 antibody titers during the convalescent phase compared with the onset phase. INTERPRETATION AND CONCLUSIONS: Our results indicate that HHV-6 infection might be associated with excessive PAIgG in some cases of ITP, and that the virus persists in a latent state. The pathogenic role of HHV-6 in ITP needs to be confirmed by further investigations.

Zinc protoporphyrin and percentage of hypochromic erythrocytes as markers of functional iron deficiency during therapy with erythropoietin in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: We assessed zinc protoporphyrin (ZPP) and the percentage of hypochromic erythrocytes in patients with advanced acquired immunodeficiency syndrome (AIDS) treated with recombinant erythropoietin (rhEPO). METHODS: Patients received 150 IU rhEPO subcutaneously every second day for 10 days, and 150 IU rhEPO plus 62.5 mg of intravenous iron every second day for an additional 10 days. RESULTS: Before rhEPO therapy, ZPP was at 64.3 +/- 27.3 micromol/mol heme and the percentage of hypochromic erythrocytes was elevated at 9.7%, indicating mild functional iron deficiency. Ferritin was 1,002 +/- 956 microg/L, with transferrin saturation of 19.1 +/- 9.7%. Under rhEPO alone, ZPP rose to 80.1 +/- 21.6 micromol/mol heme and the percentage of hypochromic red cells rose to 22.9 +/- 4.7%; ferritin fell to 705 +/- 601 microg/L and transferrin saturation fell to 12 +/- 6.3%. When rhEPO was supplemented with iron, ZPP fell to 70.4 +/- 20.5 micromol/mol heme, the percentage of hypochromic red cells fell to 14.7 +/- 3.4%; ferritin was unchanged at 771 +/- 62 microg/L and transferrin saturation rose to 20.5 +/- 5.5%. CONCLUSIONS: In contrast to ferritin and transferrin saturation, ZPP and the percentage of hypochromic erythrocytes effectively detect the functional iron deficiency under rhEPO therapy in advanced AIDS.