We report the case of an 82-year-old patient, hospitalized for malaise. Her clothes were infested by numerous insects and the entomological analysis identified them as being Cimex lectularius (bed bugs). The history of the patient highlighted severe cognitive impairment. The biological assessment initially showed a profound microcytic, aregenerative, iron deficiency anemia. A vitamin B12 deficiency due to pernicious anemia (positive intrinsic factor antibodies) was also highlighted, but this was not enough to explain the anemia without macrocytosis. Laboratory tests, endoscopy and a CT scan eliminated a tumor etiology responsible for occult bleeding. The patient had a mild itchy rash which was linked to the massive colonization by the bed bugs. The C. lectularius bite is most often considered benign because it is not a vector of infectious agents. Far from trivial, a massive human colonization by bed bugs may cause such a hematic depletion that severe microcytic anemia may result.

The foundation of laboratory hematologic diagnosis is the complete blood count and review of the peripheral smear. In patients with anemia, the peripheral smear permits interpretation of diagnostically significant red blood cell (RBC) findings. These include assessment of RBC shape, size, color, inclusions, and arrangement. Abnormalities of RBC shape and other RBC features can provide key information in establishing a differential diagnosis. In patients with microcytic anemia, RBC morphology can increase or decrease the diagnostic likelihood of thalassemia. In normocytic anemias, morphology can assist in differentiating among blood loss, marrow failure, and hemolysis-and in hemolysis, RBC findings can suggest specific etiologies. In macrocytic anemias, RBC morphology can help guide the diagnostic considerations to either megaloblastic or nonmegaloblastic causes. Like all laboratory tests, RBC morphologies must be interpreted with caution, particularly in infants and children. When used properly, RBC morphology can be a key tool for laboratory hematology professionals to recommend appropriate clinical and laboratory follow-up and to select the best tests for definitive diagnosis.

Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children.Serum hepcidin was measured by using an automated commercial immunoassay. Reference values were obtained from 86 healthy children. Hepcidin was then evaluated in 52 children with diseases where this hormone was expected to be differently regulated.Hepcidin values were 43.6 ng/mL median; 32-52.7 1-3 q: in males and 36.4 ng/mL median; 28.5-45.7 1-3 q: in females (P = 0.039). Hepcidin was significantly higher in postpubertal normal females than in normal males. Hepcidin resulted up-regulated in anemia of chronic disease of children affected by systemic Juvenile Idiopathic Arthritis and decreased after treatment with anakinra, an anti-interleukin-1 receptor antagonist. In iron deficiency anemia patients on oral iron supplementation and in β-thalassemia subjects, hepcidin levels were similar to those found in healthy subjects.This study sets up reference values for pediatric population and shows that in normal controls serum hepcidin react differently to puberty in females vs. males. In addition, it suggests that serum hepcidin may discriminate microcytic inflammatory anemia of Juvenile Idiopathic Arthritis from iron deficiency anemia. Overall these findings may represent a helpful tool for future studies tailored to understand the role of hepcidin in management of iron disorders in children.

A 6-month-old, neutered male, mixed-breed dog was examined for a 2-month persistent fever, nonhealing dermal metacarpal area wound, and leukocytosis (47.0-198.0 × 10(3)/μl). Serum chemistry findings included hypoalbuminemia, hyperglobulinemia, hyperphosphatemia, and hyperphosphatasemia. Complete blood cell count results revealed a moderate microcytic, hypochromic nonregenerative anemia with a profound leukocytosis (198.5 × 10(3)/μl), characterized by neutrophilia with toxicity and hypersegmentation, and significant band cells. Tick-borne disease titers (genera Anaplasma, Ehrlichia, and Borrelia) were negative, as were polymerase chain reaction for other infectious agents (genera Hepatozoon, Mycobacterium, Mycoplasma; and Canine distemper virus). No agents were identified in a deep dermal biopsy (conventional and special histochemical stains) of the chronic draining, metacarpal region lesion. Cytology of the draining tract revealed numerous mixed bacteria and a surprising lack of neutrophils. Chronic occult blood loss with iron deficiency was considered a possible cause of the anemia. Differentials for the leukon were chronic established inflammation (occult infectious agent), chronic neutrophilic leukemia, paraneoplastic leukocytosis (neoplastic source of granulocyte colony-stimulating factor [CSF] or granulocyte-macrophage CSF), and leukocyte adhesion deficiency (LAD). The possibility of a LAD disorder was further investigated because of the noted hypersegmented neutrophils, absence of neutrophils in the cytology sample, the animal's young age, and persistence of clinical and laboratory signs. Flow cytometry of blood neutrophils showed a 60% reduction in surface expression of the β2-integrin (CD18) subunit, whereas neutrophil function tests (oxidative burst and phagocytosis) were normal. Genetic testing revealed a homozygous missense mutation in the β2-integrin subunit gene, previously recognized only in purebred Irish Setters, leading to a diagnosis of LAD type 1 disorder in this mixed-breed dog.

Microcytic hypochromic anaemias are a result of defective iron handling by erythroblasts that decrease the haemoglobin content per red cell. Recent advances in our knowledge of iron metabolism and its homeostasis have led to the discovery of novel inherited anaemias that need to be distinguished from common iron deficiency or other causes of microcytosis. These atypical microcytic anaemias can be classified as: (i) defects of intestinal iron absorption (ii) disorders of the transferrin receptor cycle that impair erythroblast iron uptake (iii) defects of mitochondrial iron utilization for haem or iron sulphur cluster synthesis and (iv) defects of iron recycling. A careful patient history and evaluation of laboratory tests may enable these rare conditions to be distinguished from the more common iron deficiency anaemia. Molecular studies allow distinction of the different types, a prerequisite for differentiated therapy.

A 39-year-old woman was admitted to our hospital with an eight-month history of dyspnea on exertion, weakness and increasing fatigue. She reported repeated episodes of menometrorrhagia and underwent a myomectomy. She is not a vegetarian. Her menstrual bleeding: 3-5 days per month. Two months ago, she complained of burning sensation of the tongue upon swallowing food and noted brittle nails. She tolerated soft foods. On physical examination, she was pale; her nails were very thin, fragile and somewhat concave. Her oral examination showed angular stomatitis, depapillated tongue and glossitis. The clinical diagnosis was anemia and dysphagia. Laboratory tests were: Hb: 7.0g/dL, MCV: 57.42fL, MCH: 15.82 pg; leukocytes: 4,980; reticulocytes: 2.18%, reticulocyte index: 0.1%, serum iron: 21ug/dl, total iron binding capacity (TIBC): 286, transferrin saturation: 7% and serum ferritin: 27ng/ml. The peripheral blood smear showed anisocytosis and hypochromic microcytic cells. Thevenon test was negative. Abdominal ultrasound: uterine myoma. A barium swallow X-ray showed a 2-mm linear filling defect between the 4th and 5th cervical vertebrae in the anteroposterior and lateral view; it protruded from the anterior wall and reduced esophageal lumen by 60%. In the endoscopy, we found a fibrous web in the cricopharyngeal area. Serial dilatations were performed over a guidewire using Savary-Gilliard dilators with diameter up to 14 mm, improving dysphagia. She was treated with transfusional therapy and parenteral iron. She was discharged with ferrous sulfate and folic acid. The Plummer-Vinson syndrome, Paterson-Brown-Kelly or sideropenic dysphagia is characterized by dysphagia, irondeficiency anemia and upper esophageal web. The syndrome is described as very rare.

We report on a case of hereditary pyropoïkilocytosis fortuitously diagnosed in a 34-year old woman issued from Benin. Laboratory tests indicated a moderate haemolytic anaemia with a marked microcytosis. Blood film examination revealed a striking anisopoikilocytosis characterized by elliptocytes, numerous red blood cells (RBC) fragments and microspherocytes. The histogram of RBC volume distribution showed two populations of RBC: a normocytic and a very microcytic population, this later corresponding to the RBC fragmentation. These features strongly suggested a membrane disorder, particularly an hereditary pyropoïkilocytosis (HPP). The thermal unstability of the cytoskeleton was demonstrated by enhanced red cell fragmentation after in vitro exposure to heat which occurs at a lower temperature as compared to normal red cells. The diagnosis of HPP was confirmed by specialized investigations (osmotic gradient ektacytometry and erythrocytic membrane proteins electrophoresis). HPP is considered as a severe form of hereditary elliptocytosis characterized by jaundice and a severe haemolytic anaemia which usually appears during the neonatal period and the childhood. Our report is intriguing because of the delayed diagnosis of HPP in a patient who presented moderate clinical manifestations.

Maximum contaminant levels are used to control potential health hazards posed by chemicals in drinking water, but no primary national or international limits for aluminum (Al) have been adopted. Given the differences in toxicological profiles, the present evaluation derives total allowable concentrations for certain water-soluble inorganic Al compounds (including chloride, hydroxide, oxide, phosphate and sulfate) and for the hydrated Al silicates (including attapulgite, bentonite/montmorillonite, illite, kaolinite) in drinking water. The chemistry, toxicology and clinical experience with Al materials are extensive and depend upon the particular physical and chemical form. In general, the water solubility of the monomeric Al materials depends on pH and their water solubility and gastrointestinal bioavailability are much greater than that of the hydrated Al silicates. Other than Al-containing antacids and buffered aspirin, food is the primary source of Al exposure for most healthy people. Systemic uptake of Al after ingestion of the monomeric salts is somewhat greater from drinking water (0.28%) than from food (0.1%). Once absorbed, Al accumulates in bone, brain, liver and kidney, with bone as the major site for Al deposition in humans. Oral Al hydroxide is used routinely to bind phosphate salts in the gut to control hyperphosphatemia in people with compromised renal function. Signs of chronic Al toxicity in the musculoskeletal system include a vitamin D-resistant osteomalacia (deranged membranous bone formation characterized by accumulation of the osteoid matrix and reduced mineralization, reduced numbers of osteoblasts and osteoclasts, decreased lamellar and osteoid bands with elevated Al concentrations) presenting as bone pain and proximal myopathy. Aluminum-induced bone disease can progress to stress fractures of the ribs, femur, vertebrae, humerus and metatarsals. Serum Al ≥100 µg/L has a 75-88% positive predictive value for Al bone disease. Chronic Al toxicity is also manifest in the hematopoietic system as an erythropoietin-resistant microcytic hypochromic anemia. Signs of Al toxicity in the central nervous system (speech difficulty to total mutism to facial grimacing to multifacial seizures and dyspraxia) are related to Al accumulation in the brain and these symptoms can progress to frank encephalopathy. There are four groups of people at elevated risk of systemic Al intoxication after repeated ingestion of monomeric Al salts: the preterm infant, the infant with congenital uremia and children and adults with kidney disease. There is a dose-dependent increase in serum and urinary Al in people with compromised renal function, and restoration of renal function permits normal handling of systemically absorbed Al and resolution of Al bone disease. Clinical experience with 960 mg/day of Al(OH)(3) (~5 mg Al/kg-day) given by mouth over 3 months to men and women with compromised renal function found subclinical reductions in hemoglobin, hematocrit and serum ferritin. Following adult males and females with reduced kidney function found that ingestion of Al(OH)(3) at 2.85 g/day (~40 mg/kg-day Al) over 7 years increased bone Al, but failed to elicit significant bone toxicity. There was one report of DNA damage in cultured lymphocytes after high AlCl(3) exposure, but there is no evidence that ingestion of common inorganic Al compounds presents an increased carcinogenic risk or increases the risk for adverse reproductive or developmental outcomes. A number of studies of Al exposure in relation to memory in rodents have been published, but the results are inconsistent. At present, there is no evidence to substantiate the hypothesis that the pathogenesis of Alzheimer's Disease is caused by Al found in food and drinking water at the levels consumed by people living in North America and Western Europe. Attapulgite (palygorskite) has been used for decades at oral doses (recommended not to exceed two consecutive days) of 2,100 mg/day in children of 3-6 years, 4,200 mg/day in children of 6-12 years, and 9,000 mg/day in adults. Chronic ingestion of insoluble hydrated Al silicates (in kg) can result in disturbances in iron and potassium status, primarily as a result of clay binding to intestinal contents and enhanced fecal iron and zinc elimination. Sufficiently high doses of ingested Al silicates (≥50 g/day) over prolonged periods of time can elicit a deficiency anemia that can be corrected with oral Fe supplements. There is essentially no systemic Al uptake after ingestion of the hydrated Al silicates. Rats fed up to 20,000 ppm Ca montmorillonite (equivalent to 1,860 ppm total Al as the hydrated Al silicate) for 28 weeks failed to develop any adverse signs. The results of dietary Phase I and II clinical trials conducted in healthy adult volunteers over 14 days and 90 days with montmorillonite found no adverse effects after feeding up to 40 mg/kg-day as Al. Since the Al associated with ingestion of hydrated Al silicates is not absorbed into the systemic circulation, the hydrated Al silicates seldom cause medical problems unless the daily doses consumed are substantially greater than those used clinically or as dietary supplements. A no-observable-adverse-effect-level (NOAEL) of 13 mg/kg-day as total Al can be identified based on histologic osteomalacia seen in adult hemodialysis patients given Al hydroxide for up to 7 years as a phosphate binder. Following U.S. EPA methods for calculation of an oral reference dose (RfD), an intraspecies uncertainty factor of 10x was applied to that value results in a chronic oral reference dose (RfD) of 1.3 mg Al/kg-day; assuming a 70-kg adult consumes 2 L of drinking water per day and adjusting for a default 20% relative source contribution that value corresponds to a drinking water maximum concentration of 9 mg/L measured as total Al. A chronic NOAEL for montmorillonite as representative of the hydrated Al silicates was identified from the highest dietary concentration (20,000 ppm) fed in a 28-week bioassay with male and female Sprague-Dawley rats. Since young rats consume standard laboratory chow at ~23 g/day, this concentration corresponds to 56 mg Al/kg-day. Application of 3x interspecies uncertainty factor and a 3x factor to account for study duration results in a chronic oral RfD of 6 mg Al/kg-day. Of note, this RfD is 5-10 fold less than oral doses of Al silicates consumed by people who practice clay geophagy and it corresponds to a maximum drinking water concentration of 40 mg Al/L. To utilize the values derived here, the risk manager must recognize the particular product (e.g., alum) or source (e.g., groundwater, river water, clay or cement pipe) of the Al found in tap water, apply the appropriate analytical methods (atomic absorption, energy dispersive X-ray diffraction, infrared spectral analysis and/or scanning transmission electron microscopy) and compare the results to the most relevant standard. The drinking water concentrations derived here are greater than the U.S. EPA secondary maximum contaminant level (MCL) for total Al of 0.05-0.2 mg/L [40 CFR 143.3]. As such, domestic use of water with these concentrations is likely self-limiting given that its cloudy appearance will be greater than the maximum permitted (0.5-5.0 nephalometric turbidity units; 40 CFR Parts 141 and 142). Therefore, the organoleptic properties of Al materials in water determine public acceptance of potable water as contrast to any potential health hazard at the concentrations ordinarily present in municipal drinking water.

Anemia is a common concern in older people and can have significant morbidity and mortality. Because anemia is a sign, not a diagnosis, an evaluation is almost always warranted to identify the underlying cause. The purpose of this study was to study the clinical profile of elderly patients with anemia and to study characteristics of hematological types of anemia in such patients as well as the closest possible etiological profile. Hundred patients above the age of 60 years were included in the study. Clinical profile with laboratory studies of Hemoglobin and diagnostic tests to fix the etiology. Majority of patients had normocytic blood picture. Renal failure was the most common underlying chronic disease. Significant number of patients were on non steroidal anti-inflammatory drugs which could contribute to the anaemia. 14% of the patients had an underlying malignancy. 73.3% of the patients in the microcytic group had an underlying GI lesion on endoscopy. Identifying anemia as an important aspect of a comprehensive geriatric assessment is absolutely essential further to clinical detection. Confirming the type of anemia is critical to direct the investigation for profiling the etiology since it is well known that the treatment of anemia goes a long way in improving the overall outcome and quality of life.

A 28-year-old female vegetarian was referred to a specialist in internal medicine with persistent iron deficiency. Laboratory analysis revealed microcytic anaemia with low ferritin levels but normal total vitamin B12 levels. The red blood cell distribution width, however, showed a very wide variation in red blood cell sizes, indicating a coexisting vitamin B12 deficiency, which was confirmed by the low concentration of active vitamin B12. Another patient, a 69-year-old woman with a history of previous gastric surgery and renal insufficiency as a complication of diabetes mellitus, was suspected to be deficient in vitamin B12, as she had low total vitamin B12 levels and an accumulation of methylmalonic acid and homocysteine in her blood. Testing the total concentration of vitamin B12 alone has insufficient diagnostic accuracy and no accepted gold standard is available for diagnosing vitamin B12 deficiency. With the development of newer tests, such as measuring holotranscobalamin II (concentration of active vitamin B12), atypical and subclinical deficiency states can be recognized. A new approach to diagnosing vitamin B12 deficiency is presented, based upon these 2 case descriptions.