Occurrence of overwhelming gram-negative infections in splenectomised patients with thalassaemia major

Abstract

This report emphasises (1) the importance of the emergence of gram-negative organisms in the pathogenesis of overwhelming post-splenectomy infections in thalassaemics, irrespective of their age and splenectomy interval, (2) the necessity to start immediate intravenous treatment with broad spectrum antibiotics in febrile individuals and (3) to draw attention to the need of a well designed study of this problem and its prevention.In thalassaemia major, ineffective erythropoesis causes chronic haemolytic anaemia resulting in extramedullary haematopoesis, iron overload and organ dysfunction. Regular packed red cell transfusion (PRCT) to maintain the pre-PRCT level at 10.5±0.5 g/dl and iron chelating with desferrioxamine to keep the serum ferritin (SF) <2,000 ng/ml have been effective in suppressing the ineffective erythropoesis and reducing the iron burden, thus improving life quality and expectancy and delaying splenomegaly [6]. Splenectomy (SE), as indicated by increased PRCT requirement, splenomegaly and hypersplenism, is now carried out in late adolescence. Having lost the protective immune function of the spleen, patients become life-long prone to overwhelming post-splenectomy infections (OPSI) and have a higher infection rate and susceptibility to OPSI in comparison to those undergoing SE for, e.g. hereditary spherocytosis, idiopathic thrombocytopenia and trauma. OPSI are caused predominantly by encapsulated Streptococcus pneumoniae (50%-60%) with a mortality rate of 60% and less frequently by Haemophilus influenzae and Neisseria meningitidis. Infections caused by Klebsiella spp., Pseudomonas aeruginosa, E. coli, Salmonella spp. and Staphyolococcus aureus have also been reported. The current infection prophylaxis targets the encapsulated pathogens and consists of pre-SE immunisations and post-SE penicillin prophylaxis to provide protection against bacterial strains, not covered by antipneumococcal vaccine and to protect those who fail to have immune response [1,3,4,5].Of 101 homozygous b-thalassaemics managed in our department, 54 have undergone SE (increased PRCT requirement and splenomegaly). Occurrence of gramnegative OPSI in the last decade prompted us to evaluate its frequency in this cohort. The female/male ratio was 1:3, age range 8-43 years, mean age at SE 11.8 years and post-SE follow-up of 1-36 years. All patients received antipneumococcal vaccine 2 weeks prior to SE and thereafter oral prophylactic penicillin 125 mg or 250 mg twice daily according to their age. Anti-pneumococcal booster vaccination was administered at 5-year intervals. The survey revealed only eight episodes of OPSI in seven patients (13%), three males and four females, age range 10-21 years, SE interval 2-11 years, mean 5.8 years. Three patients had diabetes mellitus and one had hepatitis B. All patients presented with high fever, two had hepatic abscess, one sepsis followed 2 months later by hepatic abscess and pleuropneumonia, one multiple brain abscesses, one purulent arthritis and septic meningitis and two had purulent meningiti...

Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up

“…38,39 The excess risk of septicemia may be caused by Gram-positive or Gram-negative bacteria, as previously reported. [15][16][17] The patterns of risk and mortality in our study and in others indicate the importance of pneumococcal vaccination in this population of patients. We previously showed that antibody levels are decreased in immunocompromised individuals and patients who undergo splenectomy because of chronic lymphocytic leukemia or Hodgkin lymphoma.…”

“…[15][16][17] Immunological and hematologic abnormalities have been described as well, including depressed phagocytic activity, diminished immunoglobulin M (IgM) production, depressed T-cell function, and leukocytosis and thrombocytosis, all of which may contribute to late complications. 4,[18][19][20][21] Post-splenectomy infections may be fatal, particularly in younger patients, those with an underlying malignant disease, and during the initial years following splenectomy.…”

Peripheral development of B cells in mouse and man

“…An increased frequency and severity of infections by pneumococcus and other encapsulated bacteria ( Haemophilus influenzae , Neisseria meningitidis ) is the first and most important symptom of primary B‐cell immunodeficiency (65) and a sign of acquired immunodeficiency syndrome (AIDS) progression in human immunodeficiency virus (HIV)‐infected children. In addition, pneumococcal diseases are 20–100 times more frequent in individuals with asplenia, splenectomy, and SCD (47, 48). Prevention of infection by vaccination is still a priority, not only because of the immense number of people infected every year and of the significant frequency of serious consequences (hearing loss, sepsis, death), but also because of the increasing antibiotic resistance (20–50%).…”

“…In the adult, IgM memory B cells are reduced in spleenless individuals and in patients with pathologies leading to anatomical lesions of the spleen and consequent impaired function, such as β‐thalassemia and sickle cell disease (SCD) (manuscript in preparation). These conditions are characterized by an increased risk of infections by encapsulated bacteria (47–49), raising the question of whether protection is dependent on the physical presence of the spleen, which filters and removes bacteria from the blood, or on the availability of IgM memory B cells, generated in the spleen. Common variable immunodeficiency (CVID) is an heterogeneous immune disorder of unknown etiology characterized by reduced serum levels of all immunoglobulin isotypes and an inability to mount protective antibody responses in the presence of normal numbers of circulating B cells (50, 51).…”

Histone acetyltransferase inhibitor II induces apoptosis in glioma cell lines via the p53 signaling pathway

“…Gliomas are the most common type of primary brain tumor in adults and second most common childhood malignancy after leukemia [ 1 , 2 ]. The annual incidence of glioma is approximately 3–8 per 10 million [ 3 ].…”