Potential role of Howell-Jolly bodies in identifying functional hyposplenism: a prospective single-institute study.

Although patients with cancer and immunosuppression are at a risk of functional hyposplenism, how to detect it promptly remains unclear. Since hyposplenism allows erythrocytes with nuclear remnants (Howell-Jolly bodies [HJBs]) to appear in the peripheral blood, HJB detection by a routine microscopic examination may help identify patients with functional hyposplenism. This prospective study was thus performed to determine the underlying diseases in patients who presented with HJBs. Of 100 consecutive patients presenting with HJBs, 73 had a history of splenectomy. The remaining 27 had hematologic cancer (n = 6, 22%), non-hematologic cancer (n = 8, 30%), hepatic disorders (n = 4, 15%), premature neonates (n = 3, 11%), hemolytic anemia (n = 2, 7%), autoimmune disorders (n = 2, 7%) and miscellaneous diseases (n = 2, 7%), and their prior treatments included chemotherapy (n = 8, 30%), steroids (n = 7, 26%) and molecular-targeted therapy (n = 3, 11%). Among the 27 patients, 22 had computed tomography scans available: 3 (14%) had underlying diseases in the spleen, and the remaining 19 (86%) were all found to have a decreased splenic volume, including 11 (50%) with more than 50% of the ideal value. The present findings suggest that HJB detection identifies patients with potentially functional hyposplenism who should receive appropriate interventional treatment, such as vaccination and prophylactic antibiotics.

Crystals and Fatty Acid Abnormalities Are Not Present in Circulating Cells From Choroideremia Patients.

Purpose: To confirm whether choroideremia (CHM) is a systemic disease characterized by blood lipid abnormalities and crystals found in, or associated with, circulating peripheral blood cells of patients. Methods: Peripheral blood samples obtained from three subjects with confirmed mutations in the CHM gene and three age-matched normal controls were processed for transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fatty acids from plasma of nine male CHM subjects were analyzed and compared to reference values for a sample from a Canadian population. Results: Intracellular crystals were not observed in the cells from choroideremia-affected males. No crystals were found adherent to the external plasma membrane of red blood cells. Fatty acid profiles of patients were similar to reference values, with the exception of lower levels of nervonic acid. Conclusions: This investigation failed to observe crystals previously reported in peripheral circulating blood cells derived from CHM subjects, and showed no significant fatty acid abnormalities, not supporting the view of CHM as a systemic disease.

Effects of GlyT1 inhibition on erythropoiesis and iron homeostasis in rats.

Glycine is a key rate-limiting component of heme biosynthesis in erythropoietic cells, where the high intracellular glycine demand is primarily supplied by the glycine transporter 1 (GlyT1). The impact of intracellular glycine restriction after GlyT1 inhibition on hematopoiesis and iron regulation is not well established. We investigated the effects of a potent and selective inhibitor of GlyT1, bitopertin, on erythropoiesis and iron homeostasis in rats. GlyT1 inhibition significantly affected erythroid heme biosynthesis, manifesting as microcytic hypochromic regenerative anemia with a 20% steady-state reduction in hemoglobin. Reduced erythropoietic iron utilization was characterized by down-regulation of the transferrin receptor 1 (TfR1) on reticulocytes and modest increased iron storage in the spleen. Hepatic hepcidin expression was not affected. However, under the condition of reduced heme biosynthesis with reduced iron reutilization and increased storage iron, hepcidin at the lower and higher range of normal showed a striking role in tissue distribution of iron. Rapid formation of iron-positive inclusion bodies (IBs) was observed in circulating reticulocytes, with an ultrastructure of iron-containing polymorphic mitochondrial remnants. IB or mitochondrial iron accumulation was absent in bone marrow erythroblasts. In conclusion, GlyT1 inhibition in rats induced a steady-state microcytic hypochromic regenerative anemia and a species-specific accumulation of uncommitted mitochondrial iron in reticulocytes. Importantly, this glycine-restricted anemia provides no feedback signal for increased systemic iron acquisition and the effects reported are pathogenetically distinct from systemic iron-overload anemias and erythropoietic disorders such as acquired sideroblastic anemia.

Hyposplenism: comparison of different methods for determining splenic function.

Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different methods for determining splenic function. Eighteen patients with SCD (i.e., 10 heterozygous (SC) and 8 homozygous (SS) SCD patients), and eight splenectomized patients were compared to 10 controls. All subjects underwent spleen scintigraphy, after which functional splenic volumes (FSV) were calculated. FSV was compared to immunological function and B cell-subsets, as well as phagocytic function represented by the presence of Howell Jolly bodies (HJB) and percentages of pitted red cells (PIT). Heterozygous SCD (SC) patients had increased splenic volumes, but diminished FSV, homozygous SCD (SS) patients were asplenic. Splenectomized and SS patients had a strongly reduced phagocytic and immunological function. SC patients had reduced anti-polysaccharide responses without an increase in PIT. FSV correlated significantly with phagocytic and immunological function. HJB were indicative of splenic dysfunction, HJB absence was not indicative of normal functioning splenic tissue. Although visualizing HJB is methodologically advantageous to PIT, both are valid biomarkers of splenic dysfunction. The amount of non-switched memory B cells is strongly correlated to FSV.

Feto-placentary pathology in human parvovirus B19 infection.

In view of the scarce references concerning the histological data in congenital parvovirus human B19 infection, we intend to provide a description of the pathological features observed in six autopsies. The virus was detected by DNA hybridization (ISH-DBH), PCR and electronmicroscopy (EM) in paraffin-embedded feto-placentary tissues. These cases constitute a subset from 86 Non Immunologic Hydrops Fetalis (NIHF) cases, in which a systemic complex of inflammatory/degenerative lesions of unknown etiology was visualized by optical microscopy. In one case a syphilitic process was detected, typefying a double infection. All fetuses showed a similar pathology--hydrops, hepato-splenomegaly, lung hypoplasia and erythroblastemia, the specific histological feature being the presence of intranuclear inclusions in the erythroid progenitors, in the erythropoietic visceral tissue and in blood marrow. Complex cardiopathy allied to abnormal lung lobulation and polisplenia were observed once; in 2 cases endocardial fibroelastosis was diagnosed. The pulmonary lesions were represented by dysmaturity allied to interstitial mononuclear infiltration. The hepatic consisted of cholestasis, portal fibrosis, canalicular proliferation, hemossiderosis, focal necroses and giant cell transformation. The central nervous system lesions were predominantly anoxic although the autolysis impaired a correct diagnosis.

[The pitting function of the spleen visualized in a patient]. / Miltens plukkfunksjon synliggjort hos en pasient.

A patient with sideroblastic anemia was splenectomized. After the splenectomy numerous inclusions were present in the erythrocytes, whereas there were almost none before the splenectomy.

Howell-Jolly body-like inclusions in the neutrophils of patients with acquired immunodeficiency syndrome.

The authors have observed discrete, densely basophilic inclusions in the peripheral blood neutrophils of 10 patients with acquired immunodeficiency syndrome (AIDS) and two additional patients without documented evidence of human immunodeficiency virus seropositivity. These inclusions were seen in 3 of 25 (12%) patients with AIDS in a retrospective review. Gram, periodic acid-Schiff, and Gomori methenamine silver stains failed to demonstrate staining of these bodies; however, the Feulgen reaction was positive. The inclusions may represent "apoptotic" nuclear fragments and thus may be similar to Howell-Jolly bodies of normoblasts in abnormal erythropoiesis. An association of these inclusions with nucleoside analogue antiviral therapy is indicated. These inclusions must be differentiated from intracytoplasmic infectious agents, Döhle bodies, and inclusions of inherited disorders.

Absorbable mesh splenorrhaphy for severe splenic injuries: functional studies in an animal model and an additional patient series.

Polyglycolic acid mesh has been introduced as a method of controlling hemorrhage in severely damaged spleens. This study examines the effect of splenic wrapping on the immune function of the spleen, and also on its ability to control splenic bleeding in trauma patients. Thirty purebred beagle dogs were divided into three groups and subjected to sham operation (Group 1), splenectomy (Group 2), and splenic wrap (Group 3). Immunologic studies showed no difference between the wrapped group (Group 3) and those with their spleens intact (Group 1) in the induction of specific antibody-producing lymphocytes in splenic tissue after the injection of attenuated Pneumococci. All splenic injuries treated at Cook County Hospital between January 1985 and May 1988 were retrospectively analyzed. Of 60 patients with splenic injuries, 14 underwent mesh splenorrhaphy without mortality or serious complications. This study demonstrates that the immune function of spleen is preserved following mesh splenorrhapy, and that this technique can be used in a clinical setting with safe and efficacious results.

Molecular basis for dominantly inherited inclusion body beta-thalassemia.

Analysis of the molecular basis of dominantly inherited beta-thalassemia in four families has revealed different mutations involving exon 3 of the beta-globin gene. It is suggested that the phenotypic difference between this condition and the more common recessive forms of beta-thalassemia lies mainly in the length and stability of the abnormal translation products that are synthesized and, in particular, whether they are capable of binding heme and producing aggregations that are relatively resistant to proteolytic degradation.

Formation of intracellular vesicles in neonatal and adult erythrocytes: evidence against the concept of neonatal hyposplenism.

Intraerythrocytic vesicles accumulate in the peripheral blood as a result of impaired clearance of these intracellular inclusions by the spleen. The observation that neonates demonstrate an increased percentage of erythrocytes containing these vesicles constitutes the primary evidence supporting the concept that the newborn is functionally hyposplenic. Neonatal erythrocytes also demonstrate an increased propensity to undergo a variety of endocytic processes. We therefore questioned whether the increase in red cell vesicles in the neonate might be the result of increased vesicle formation as opposed to impaired splenic clearance. Newborn and adult erythrocytes were incubated in vitro in synthetic medium at 37 degrees C. Several parameters confirmed the maintenance of physiologic conditions, including levels of erythrocyte phosphate metabolites monitored by nuclear magnetic resonance. The acquisition of intraerythrocytic vesicles during the course of these incubations was compared. Over a period of 144 h, 19.2% of neonatal erythrocytes acquired vesicles compared to 3.7% of the adult cells (p less than 0.001). The increase in vesicles was greater in younger density-separated erythrocytes in both the neonate (37.6%, p less than 0.0005) and the adult (10.3%, p less than 0.002), but persisted even in the oldest erythrocytes (12.2% and 2.4%, respectively). We conclude that the increase in erythrocytic vesicles in the neonate may not simply be an indication of hyposplenism, but a reflection of increased vesicle formation which overwhelms the clearance capability of the spleen.

Maturation of Howell-Jolly bodies observed in a case of malignant histiocytosis.

The maturation of Howell-Jolly bodies was microscopically observed on the May-Grünwald-Giemsa-stained film of bone marrow obtained from a patient with malignant histiocytosis. The bodies separated from the nucleus at the polychromatophilic normoblast stage and condensed faster than the main nucleus before denucleation in the normoblast stage.