Associated occurrence of persistent truncus arteriosus and asplenia

Summary An infant with persistent truncus arteriosus associated with splenic agenesis and the asplenia syndrome is reported, including clinical, echocardiographic and autopsy findings. To the authors' knowledge this association has not been previously reported.     

Abnormalities of Intestinal Rotation in Patients with Congenital Heart Disease and the Heterotaxy Syndrome

Objective. Abnormalities of intestinal rotation (AIR) are seen in association with congenital heart disease and heterotaxy syndrome. The prevalence of these abnormalities and recommendations for management are unclear. Our objective was to determine the prevalence of screening for AIR by elective imaging among our group and prophylactic vs. emergent surgical intervention for AIR in patients with congenital heart disease and heterotaxy syndrome. Methods. From October 1988 through October 2000, we identified 74 patients with congenital heart disease and heterotaxy syndrome, 44 (59%) asplenia, 30 (41%) polysplenia. Abdominal imaging was performed in 34 patients (45%). Twenty-four (32%) were found to have AIR. Of 34 patients imaged, 22 (65%) were found to have AIR. Two patients not imaged were found to have AIR: one at autopsy, and the other, incidentally during other abdominal surgery. Because imaging was performed based on individual cardiologist’s practice style that did not change over the period of the study and rarely secondary to symptoms, it is likely that the prevalence of AIR in the patients that were not electively imaged would be similar. Results. There was no statistical difference in the presence of AIR between asplenic (34%[15/44]) and polysplenic (30%[9/30]) patients. Of the 22 patients imaged with AIR, 18 underwent Ladd procedure. Five of 12 imaged patients without AIR were found to have other significant gastrointestinal pathologies requiring intervention including gastrostomy tube placement for reflux (3), duodenal web (1), and biliary atresia (1). Of the 40 patients who were not pre-emptively imaged, none suffered acute obstruction solely secondary to AIR. However, in 2 patients intestinal obstruction was suspected and subsequently discovered by imaging and/or laparotomy due to other intestinal anomalies. Conclusions. AIR is common among patients with heterotaxy syndrome and congenital heart disease. We recommend that patients with congenital heart disease and heterotaxy syndrome have routine elective abdominal imaging of their gastrointestinal tract at birth as part of their evaluation.     

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008–2020

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.     

Association of hiatus hernia with asplenia syndrome

During a 13-month period, 13 patients with asplenia syndrome were evaluated with MRI for cardiovascular and visceral anomalies. The MR images were reviewed for the presence of hiatus hernia which was found in three patients. One of the remaining ten patients with no MRI evidence of hiatus hernia was diagnosed as having gastro-oesophageal reflux and hiatus hernia by an oesophagogram and 24-h pH monitoring. This patient had undergone fundoplication prior to MRI. Out of the 13 patients (31%) with asplenia syndrome, 4 had hiatus hernia. It appears that among patients with the asplenia syndrome, hiatus hernia is a frequent finding. Recurrent pneumonia or bronchiolitis in patients with asplenia syndrome requires evaluation for the presence of hiatus hernia and gastro-oesophageal reflux.     

Right Atrial Isomerism in Four Siblings

Heterotaxy syndromes, right or left atrial isomerism, result from disruption of left–right axis determination and their manifestations include complicated heart defects. Recent studies in model organisms have revealed complex genetic pathways and several genes involved in this process. In affected humans, however, molecular studies have identified mutations in a small number of individuals, while in most the cause remains unknown. Furthermore, although family data suggest, autosomal recessive inheritance, such genes have not yet been identified. We have studied six members of a family, four children affected with right atrial isomerism (RAI) and their healthy parents, for disturbances of left–right axis development. The children, one female and three males who all had complicated heart defects, succumbed and had an autopsy. Their nonconsanguineous parents were examined by cardiac and abdominal ultrasound or MRI. In all four children the heart defects included single ventricle with dysplastic atrioventricular (AV) valve, total anomalous pulmonary venous drainage (TAPVD), and malposition of great arteries (MGA) with pulmonary stenosis (PS). All had asplenia; two also had dextrocardia and abdominal situs inversus. The diagnosis of RAI was made postnatally in the first child and prenatally in others. Two siblings had no surgery and died as a newborn, one with obstructed supracardiac TAPVD and the other with regurgitating AV valve. Two children underwent heart surgery. One had repair of obstructive infracardiac TAPVD but died in infancy. The other underwent both hemi-Fontan operation and heart transplantation but died at the age of 2 years. This is the first report describing four children with RAI in the same family. The occurrence of RAI in male and female siblings without any indication of left–right axis abnormalities in their parents suggests autosomal recessive inheritance of human isomerism.     

Haemophilus influenzae type b capsular polysaccharide antibody levels in Japanese young patients with hematological malignancies and asplenia

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 μg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 μg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.     

Immunogenicity,safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2–17-year-old children with asplenia or splenic dysfunction: A phase 3 study

BackgroundImmunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population.MethodsThis phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2–4, 5–10 and 11–17 years), was conducted in Poland and the Russian Federation. For the 2–4 years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2 months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31 days post-vaccination, respectively, and serious AEs (SAEs) throughout the study.ResultsOf 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2 µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child.ConclusionPHiD-CV was immunogenic and well tolerated in 2–17-year-old children with asplenia or splenic dysfunction.Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.     

Pathology and embryology of common atrioventricular canal

This paper focuses on the terminology, classification, pathologic anatomy, embryology, and etiology of common atrioventricular (AV) canal. The designation common AV canal is preferred because it includes both the characteristic septal and leaflet defects; i.e. common AV canal is much more than an AV septal defect, as the cleft in the anterior mitral leaflet indicates. This cleft is indeed a cleft (not a commissure), and the left-sided AV valve is a malformed mitral valve (not a trileaflet non-mitral valve). Common AV canal is classified as complete, partial, transitional, intermediate, balanced, left ventricular type, and right ventricular type. The complete form is subclassified as Rastelli types A, B, and C. The normal embryology of AV canal division is presented in man and in the rat. In humans, the superior and inferior endocardial cushions of the AV canal normally fuse during Streeter’s horizon XVII, i.e. 34–36 days of age. An understanding of the spatial geometry of the endocardial cushions of the AV canal relative to the ventricular and atrial septa helps to explain normal and abnormal development and the classification of common AV canal. Normal morphogenesis is a three-step process. An increase in fibroblast cell-surface adhesiveness may well be important in the morphogenesis of common AV canal in Down syndrome. Etiologically, a single gene stochastic model is now thought more likely than the polygenic multifactorial hypothesis. The Down syndrome congenital heart disease gene (or genes) is (are) now thought to be located on chromosome 21 from q22.1 to q22.3. Common AV canal may be non-syndromic or syndromic, the latter including Down syndrome and the heterotaxy syndromes with asplenia and polysplenia. There are statistically highly significant differences between Down and non-Down canals, and between asplenic and polysplenic canals.     

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.