Splenic Dysfunction Research Articles

Management of the Cancer Patient With Infection and Neutropenia

Infections are major causes of morbidity and mortality in cancer. The intensity and duration of immunosuppressive chemotherapy determine the risk. Cancer may be associated with immune defects, in particular hematologic malignancies. Predisposing factors include tumor site, intravenous devices, neutropenia due to underlying disease, mucosal lesions, corticosteroids, monoclonal antibodies, splenic dysfunction, and treatment with chemotherapy or radiation therapy. Bacteremia is documented in approximately 25% of people with febrile neutropenia. The drug choice for empiric therapy is influenced by factors related either to the patient or to the institution. Guidelines and general statements should always take local epidemiology into consideration. The therapeutic hematopoietic growth factors should be reserved for patients with fever and neutropenia and those at high risk for infection-associated complications or poor clinical outcomes. The Multinational Association of Supportive Care in Cancer (MASCC) has developed a Risk Index that predicts the risk of medical complications and outcome.

1456 A Survey of Paediatricians Practices and Knowledge About Pneumococcal Vaccines in High Risk Children Before the Era of Universal Immunisation

Aims and Background: We aimed to assess the knowledge and practice of paediatricians in the Trent region of England about the Chief Medical Officer's (CMO) recommendations for the pneumococcal vaccines (PV) to high-risk children before the introduction of the vaccine into the routine universal immunisation programme in Sept 2006. Methods and Design: A total of 68 self-administered questionnaires were returned from a total of 100 posted out to paediatricians in the Trent region. Results: 89% of the paediatricians were aware of the CMO's recommendations of pneumococcal and influenza vaccines to high risk children. The most correctly identified high risk groups for PV were children with asplenia / splenic dysfunction (71%), chronic lung disease (69%), previous invasive pneumococcal disease (65%), congenital heart disease (63%), neuromuscular diseases (59%), nephrotic syndrome (57%), cystic fibrosis (54%) and chronic heart failure (54%). Table 1 The least correctly identified high-risk groups were children previously admitted for asthma or a lower respiratory tract disease (9% each), cirrhosis (28%), patients with CSF shunts (31%), following renal transplant (37%), on chemotherapy or steroids (38%) and chronic liver diseases (38%). Conclusion: Most paediatricians were aware of the CMO's recommendations on pneumococcal vaccines for high-risk children. This knowledge however was poorly translated into correct advice given to patients. The introduction of PV into the universal immunisation schedule would enable all the high-risk children to be optimally protected and not subjected to the unreliable knowledge of their busy paediatricians and ”postcode lottery” effect.

1455 A Survey of Paediatricians‚ Knowledge and Practices About Influenza Vaccines in High Risk Groups of Children

Aims and Background: We aimed to assess paediatricians‘ awareness of Chief Medical Officer’s (CMO) recommendations in relation to influenza vaccination of high risk children in the Trent region of England. Methods: A questionnaire was posted out to 100 consultant paediatricians. A total of 68 questionnaires were returned and analysed. Results: 41% and 49% of the respondents were working in tertiary and district hospitals respectively. 89% of them claimed to be aware of the CMO's newsletters which listed the high-risk groups of children requiring influenza vaccines. The highest rates of vaccine recommendation were for children with chronic lung disease (70.5%), congenital heart disease (68%), cystic fibrosis (66%), chronic heart failure (63%), asthmatics requiring regular steroids (62%), neuromuscular diseases (59%), severe splenic dysfunction (59%), children aged below 5 years with previous invasive pneumococcal disease (56%), diabetes mellitus (53%) and chronic renal failure (48.5%). The lowest rates of vaccine recommendations included nephrotic syndrome (43%), post renal transplant (41%), chronic liver disease (35%), cirrhosis (26%), HIV/AIDS (37%), children on chemotherapy/steroids (38%), previously admitted for asthma (22%) or with a lower respiratory tract disease (9%). Conclusion: Most paediatricians were aware of the CMO recommendations on influenza vaccines for high risk children. This knowledge however was not always translated into correct advice given to patients in routine clinical practice. We recommend that regular education and training for the busy practising paediatricians should be undertaken to ensure that continual high quality of care is rendered to children who need to be vaccinated with the Influenza vaccine.

Pneumococcal sepsis presenting as purpura fulminans in a healthy infant

The majority of cases of purpura fulminans are associated with Neisseria meningitidis sepsis. However, other bacteria, including Streptococcus pneumoniae, can also be the cause. Underlying predisposing conditions are immunodeficiencies and splenic dysfunction, the latter being the most frequent in the paediatric age group. Purpura fulminans secondary to pneumococcal sepsis in a healthy infant is described.

Organ-o-penia

the loss in appendicular muscle and bone mass with increasing age is a well-defined event ([4][1], [11][2]). While this event has been acknowledged for centuries, in vivo data to quantify the degree of age-related changes in muscle and bone mass have only become available, primarily due to new

The spleen in the sickling disorders: an update

In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal "autosplenectomy" emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management.

Asplenia and functional hyposplenism in autoimmune polyglandular syndrome type 1

Asplenia was diagnosed in four patients with autoimmune polyendocrine syndrome type-I (APS-I): two children, aged 2-4 years, from the same family and two adults, the father of the two children and his cousin. We have observed a worsening in splenic function in the children during a follow-up of a few years. Patients with APS-I should be evaluated for splenic function, since splenic dysfunction has important therapeutic implications, especially in children.

Morphological and functional platelet abnormalities in Berkeley sickle cell mice

Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37 ± 3.2 vs. 27 ± 1.4, mean ± SD; p < 0.001), in association with moderate thrombocytopenia (505 ± 49 × 10 3/μl vs. 1151 ± 162 × 10 3/μl; p < 0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell–Jolly bodies and “pocked” erythrocytes ( p < 0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5 ± 1% vs. 1 ± 1%; p < 0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease.

L‐arginine reverses Radiation‐induced immune dysfunction: the need for optimum treatment window

The aim of the present study was to investigate the protective efficacy of L‐arginine (LA), in mitigating gamma radiation‐induced injury in mice. Administration of LA at +2 h after 2‐Gy total body gamma radiation (TBI) was effective in preventing, the decrease in spleen size, weight and splenocyte number caused by TBI (Fig. 1a). LA administration at +2 h of TBI also prevented specific antibody response of splenic B cells to sheep red blood cells (Fig. 2). Splenic DNA fragmentation, which was significantly increased in TBI mice, was significantly reduced by the administration of LA at +2 h of TBI (Fig. 3). However, LA administered just before TBI did not reverse the radiation‐induced splenic damage. Serum nitrite levels in mice administered with LA just before TBI, were significantly higher, when compared to levels in mice, administered with LA at +2 h of TBI. The results suggest the importance of the correct therapeutic window of administering LA in mitigating the radiation induced host splenic immune dysfunction.

Sudden Death Caused by Fulminant Bacterial Infection: Background and Pathogenesis of Japanese Adult Cases

To analyze a risk factor for the onset of fulminant bacterial infection. Nine unexpected acute death cases were clinicopathologically analysed. All cases represented the sudden onset of shock symptom, led to acute death within a few days, and later bacteremia was identified. Pathogens were Streptococcus pneumoniae (S. pneumoniae) (5 cases), group A beta Hemolytic Streptococcus pyogenes (S. pyogenes) (3 cases), and Vibrio vulnificus (V. vulnificus) (1 case). Seven of the nine patients had underlying chronic illness. S. pneumoniae infection was associated with splenic dysfunction, and group A beta Hemolytic S. pyogenes and V. vulnificus infections were associated with alcoholic liver injury. Group A beta hemolytic S. pyogenes and V. vulnificus infections involved necrotizing fasciitis, and alcoholic liver cirrhosis was confirmed in two of the four patients. Despite the different type of bacteria, the onset of fulminant bacterial infection depended upon depressed bacterial phagocytosis in the liver or spleen. Underlying chronic illnesses should be identified as a predisposing common risk factor. It is important to understand the relations between underlying chronic illness and the onset of fulminant infection.

Uptake of pneumococcal polysaccharide vaccine in at-risk populations in England and Wales 1999–2005

The UK has had a pneumococcal polysaccharide vaccination (PPV) programme for groups at higher risk of invasive disease since 1992. This paper presents data from a sample of primary-care practices (Q-RESEARCH) of PPV uptake in patients according to their risk status. Of 2.9 million registered patients in 2005, 2.1% were vaccinated with PPV in the preceding 12 months and 6.5% in the preceding 5 years. Twenty-nine per cent of the registered population fell into one or more risk groups. The proportion of each risk group vaccinated in the previous 5 years ranged from 69% (cochlear implants), 53.4% (splenic dysfunction), 36.5% (chronic heart disease), 34.7% (diabetes), 22.9% (immunosuppressed), 28.7% (chronic renal disease), 15.9% (sickle cell disease) to 12.6% (chronic respiratory disease). Uptake was lower in areas where the non-white proportion of population was >10%. In conclusion, there remain large gaps in the uptake of PPV in several high-risk populations in the United Kingdom. Effective strategies need to be developed to address these deficiencies.

Questions and answers on immunization

QUESTION: What constitutes optimal pneumococcal immunization for children with splenic dysfunction or asplenia?

Controlling invasive pneumococcal disease: is vaccination of at-risk groups sufficient?

SummaryRisk factors for invasive pneumococcal disease (IPD) include young and old age, comorbidities (such as splenic dysfunction, immunodeficiencies, chronic renal disease, chronic heart or lung disease or cerebral spinal fluid leak), crowded environments or poor socioeconomic conditions. Universal use of the 7-valent pneumococcal conjugate (7vPncCRM) vaccine for infants and young children has led to significant decreases in IPD in the vaccinated population (direct protection), and there has also been a decrease in the incidence of IPD among the nonvaccinated population (indirect immunity; herd protection). While 7vPncCRM vaccine is administered universally to children in USA, many countries of the European Union have chosen to target children with comorbidities. This review aims to highlight individual risk factors for IPD, describe studies that evaluated pneumococcal conjugate vaccines in at-risk groups and estimate the proportion of at-risk children who may have been vaccinated in the European Union since the 7vPncCRM vaccine was introduced, using UK as an example. Although immunisation targeting only children with comorbidities may achieve satisfactory results for a few, many otherwise healthy children at risk simply because of their age will be neglected, and herd protection might not be established.

Clarifying anatomical complexity: Diagnosing heterotaxy syndrome in the fetus

Heterotaxy syndrome, a disorder that involves abnormal lateralization of the abdominal viscera, thoracic organs and cardiac atria, remains one of the most challenging lesions in the field of pediatric cardiology both from a diagnostic and surgical strategy standpoint. Despite improved techniques, heterotaxy syndrome continues to be associated with high morbidity and mortality. Generally, heterotaxy syndrome can be categorized into two subtypes. Right atrial isomerism is associated with single ventricle, atrioventricular canal defect, pulmonary outflow obstruction, conotruncal abnormalities, bilateral superior vena cavae and total anomalous pulmonary venous connection. Left atrial isomerism can have similar intracardiac findings but also includes interruption of the inferior vena cava, ipsilateral pulmonary venous connection and complete heart block. Non-cardiac abnormalities such as splenic dysfunction, intestinal malrotation, and biliary atresia can be seen in both subtypes. Prenatal diagnosis of heterotaxy syndrome requires thorough knowledge of the typical findings as well as a systematic approach to the segmental anatomy. Accurate prenatal diagnosis is helpful to appropriately counsel families and for the perioperative management of these patients. However, the impact of prenatal diagnosis on long-term outcome remains to be seen.

Questions and answers on immunization

QUESTION: What constitutes optimal pneumococcal immunization for children with splenic dysfunction or asplenia?

The absent and vanishing spleen: Congenital asplenia and hyposplenism-two case reports

Two unrelated patients are reported: one with isolated familial asplenia diagnosed postmortem, the other with isolated hyposplenism diagnosed after recurring invasive bacterial infections. Because both children died of fulminant septic shock, the importance of early diagnosis of splenic dysfunction is evident. Clues for an early diagnosis of congenital asplenia are recurrent invasive bacterial infections, Howell-Jolly bodies in the blood smear or a relative with congenital isolated asplenia. Although the guidelines for infection prevention in asplenism--patient education, antibiotic prophylaxis and vaccination--are well defined, controversy remains as to how to differentiate hyposplenism from functional asplenism. Based on the present observations, we define a patient as functionally asplenic--and therefore at risk for life-threatening infections-when Howell-Jolly bodies are present in the blood smear, a very small spleen is found by ultrasound, or splenic blood flow is compromised.

Mild-phenotype sickle cell disease: molecular basis, clinical presentation and management recommendations

<h2>Summary</h2> Although sickle cell disease (SCD) is monogenic, its clinical presentation is highly heterogeneous. Many of the modulating factors are genetically determined while others are environmental. The <i>β</i>-globin gene haplotype, level of fetal haemoglobin and co-inheritance of <i>α</i>-thalassaemia trait are some of the genetic factors. Many SCD patients in the Arabian Peninsula have the Arab/India haplotype and are characterized by elevated Hb F levels. They tend to have a mild phenotype, presenting with fewer pain episodes and less anaemia. Stroke, leg ulcers, acute chest syndrome, priapism and early splenic dysfunction are uncommon. Management of acute episodes does not differ from usual recommendations, but the use of routine penicillin prophylaxis to prevent pneumococcal sepsis may not be mandatory.

Administration of tolerogenic dendritic cells induced by interleukin-10 prolongs rat splenic allograft survival

The risk and intensity in splenic graft rejection are greater than in other types of transplants, because the spleen is the largest peripheral lymphoid organ and the immunosuppressive drugs administered can cause splenic dysfunction. In this study, we demonstrate that intravenous injection of interleukin-10–treated donor-type dendritic cells into recipient rats prolongs the survival of splenic allografts. Although the mechanisms are not clear, the induction of tolerance to grafted spleens seems to rely mainly on blockage of expression of the costimulatory molecule CD86, by interleukin-10, leading to enhanced apoptosis of allospecific T cells by immature and tolerogenic dendritic cells. Administration of tolerogenic cells induced by interleukin-10 may thus represent a useful approach for protection of splenic allografts. Further study is required to investigate the operative pathways and to optimize the strategy targeting dendritic cells to induce tolerance in splenic allografts.

Salmonella as a Causative Organism of Various Infections in Patients with Sickle Cell Disease

Patients with sickle cell disease (SCD) are susceptible to a variety of bacterial infections, including infections caused by Salmonella species. We sought to identify the most common infections caused by Salmonella spp. in SCD patients at our hospital, and to determine their mortality rates and susceptibility to commonly used antimicrobial agents. We conducted a retrospective review of all Salmonella infections in SCD patients admitted to Qatif Central Hospital during the last 11 years. During the 11 years of the study, 331 episodes of Salmonella infection occurred in 319 patients. The incidence of Salmonella infection in SCD patients was 11.5% compared to only 0.65% in the general hospital population. The commonest sites of Salmonella infection were blood (42% of isolates), followed by gastrointestinal tract (23.5%) and the skeletal system (22.5%). Salmonella infection was commonly seen in patients less than 15 years of age. The case fatality rate in patients with Salmonella sepsis was 2.2% (3/139), but there were no deaths associated with other types of Salmonella infections. Ampicillin and cotrimoxazole resistance occurred in 29% and 24% of the isolates, respectively, but only 0.6% were resistant to ceftriaxone and 1.8% had intermediate resistance to ciprofloxacin. Salmonella is a common cause of sepsis and osteomyelitis in patients with SCD in our locality. Empirical antimicrobial therapy should cover the likely pathogens, including Salmonella species.

SPLENIC FUNCTION IN OMANI CHILDREN WITH SICKLE CELL DISEASE: Correlation with Severity Index, Hemoglobin Phenotype, Iron Status, and α -Thalassemia Trait

The prevalence of functional asplenia in Omani children with sickle cell disease (SCD) has not been previously defined. In this study, the authors aim to compare the natural history of splenic dysfunction in their patients to other reports. The splenic function was studied in 72 Omani patients with sickle cell disease (50 homozygous for hemoglobin S (HbS-S), 11 double heterozygotes for HbS and g 0 -thalassemia (HbS- g 0 -thal), 5 HbS- g + -thal, 5 patients with hemoglobin S-D disease, and 1 child with hemoglobin S oman trait) aged 4.8-16 years, using 99m Tc-labeled tin colloid scintigraphy. The study revealed 4 groups according to their colloid uptake: group I included 20 patients (28%) with normal splenic function; group II, 6 patients (8%) with mild hyposplenism; group III, 20 (28%) with severe hyposplenism; and group IV, 26 (36%) patients with functional asplenia. Overall, more than 60% of them had preserved splenic function. Except for HbS- g + patients, the developmental pattern of hyposplenism was not different among the different Hb phenotypes. Factors associated with preservation of spleen function in these patients were larger splenic size ( p < .01), less clinical severity ( p < .05), lower MCH ( p < .01), higher HbF ( p < .001), and presence of f -thalassemia trait ( p < .05).