A child with severe iron-deficiency anemia and a complex TMPRSS6 genotype.

OBJECTIVES: We report a case of a 7-year-old girl with severe hypochromic microcytic anemia, who was unresponsive to classical iron supplements. We suspected IRIDA, iron-refractory iron-deficiency anemia, a genetic iron metabolism disorder, caused by TMPRSS6 variations. TMPRSS6 encodes matriptase-2, a negative regulator of hepcidin, and its pathological variants are related to normal to high levels of hepcidin. We analyzed the TMPRSS6 gene and we improved clinical management of the patient, selecting the appropriate supplementation therapy. Intervention & Technique: The parenteral iron therapy was started, but the patient was only partially responsive and the anemia persisted. To confirm the diagnosis, the TMPRSS6 gene sequence was analyzed by DNA sequencing and other relevant biochemical parameters were evaluated. RESULTS: The TMPRSS6 sequence analysis showed a complex genotype with a rare heterozygous missense variant, in addition to other common polymorphisms. The serum hepcidin value was normal. We unexpectedly observed a normalization of patient's hemoglobin (Hb) levels only after liposomal iron treatment. DISCUSSION AND CONCLUSION: The proband was symptomatic for IRIDA during a critical phase of growth and development, but we did not find a clearly causative genotype. A long-term result, improving stably patient's Hb levels, was obtained only after liposomal iron supplementation. Children may be at greater risk for iron deficiency and the degree of anemia as well as the response to the iron supplements varies markedly patient to patient. Here, we show the importance of comprehensive study of these patients in order to collect useful information about genotype-phenotype association of genes involved in iron metabolism.

Anemia in patients on chronic hemodialysis in Cameroon: prevalence, characteristics and management in low resources setting.

BACKGROUND: Anemia is a common complication of chronic kidney disease. We investigated the prevalence, characteristics and management of anemia in patients on chronic hemodialysis and assessed the response to blood-transfusion based management in Cameroon. METHODS: This was a cohort study of five months' duration (August-December 2008) conducted at the Yaoundé General Hospital's hemodialysis center, involving 95 patients (67 men, 70.5%) on chronic hemodialysis by a native arteriovenous fistula. A monthly evaluation included full blood counts, number of pints of red cell concentrates transfused, and vital status. RESULTS: At baseline, 75 (79%) patients had anemia which was microcytic and hypochromic in 32 (43%). Anemia was corrected in 67 (70.5%) patients using blood transfusion only, while 28 (29.5%) patients were receiving erythropoietin (11 regularly, 39%). Only 77.2% of 342 pints (median 3.0, range 0-17 per patients) of red cell concentrates prescribed were effectively received during the follow-up at an unacceptably high cost to patients and families. Mean hemoglobin and mean corpuscular hemoglobin levels remained stable during follow-up, while mean corpuscular volume increased. Erythropoietin treatment was the main determinant of favorable trajectories of hematological markers. CONCLUSIONS: Patients on chronic hemodialysis have predominantly microcytic hypochromic anemia, with limited capacity for correction using blood transfusion.

Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis.

During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel molecular discoveries in clinical practice has increased our understanding of the presentation, diagnosis, and management of these diseases. Integration of these insights into daily clinical practice will reduce delays in establishing a proper diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even detrimental treatments. To assist the clinician, we developed evidence-based multidisciplinary guidelines on the management of rare microcytic anemias due to genetic disorders of iron metabolism and heme synthesis. These genetic disorders may present at all ages, and therefore these guidelines are relevant for pediatricians as well as clinicians who treat adults. This article summarizes these clinical practice guidelines and includes background on pathogenesis, conclusions, and recommendations and a diagnostic flowchart to facilitate using these guidelines in the clinical setting.

How I manage patients with atypical microcytic anaemia.

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.

[Diagnosis of hypochromic microcytic anemia in children]. / Exploration d'une anémie microcytaire chez l'enfant.

Iron deficiency is the most frequent cause of hypochromic microcytic anemia in children, but other causes, some of them requiring specific management, may be involved. Checking the iron-status is absolutely mandatory. When iron-status parameters are low, inadequate intake, malabsorption, blood loss, and abnormal iron utilization must be tested. In absence of iron deficiency, α- and ß-globin and heme biosynthetic gene status must be checked. Assessing the iron stock level is difficult, because there is an overlap between the values observed in iron-replete and iron-deprived patients, so that at least 2 iron-status parameters must be below normal for diagnosing iron deficiency. Furthermore, inflammation may also mimic some characteristics of iron deficiency. Diagnosing iron deficiency leads to prescribing iron supplementation with follow-up at the end and 3 months after cessation of treatment. When iron stores are not replete at the end of treatment, compliance and dosage must be reevaluated and occult bleeding sought. The latter is also required when the iron store decreases 3 months after cessation of iron replacement.

Chronic massive fetomaternal hemorrhage in a newborn from immigrants. Clinical and organizational implications.

Fetomaternal hemorrhage (FMH) refers to the entry of fetal blood into the maternal bloodstream before or during delivery. FMH of more than 30 mL occurs with the frequency of about 1/300. Fetal outcomes may be compromised by still births, hydrops fetalis, cardiac complications, and increased rates of postpartum infant death. In most cases, the cause is not identified. Clinical manifestations of FMH depend on the volume of blood lost and the rate that it occurred. We report a case of chronic massive FMH in a newborn of an immigrant mother with a favorable outcome. Medical visits and tests during pregnancy, including ultrasound scans, were not performed. The baby was hemodynamically stable after birth, manifesting only pallor. The complete blood count revealed severe hypochromic anemia (hemoglobin 3,8 g/dl, hematocrit 14,4%) and reticulocytosis (reticulocyte 25,2%). There was no ABO blood type incompatibility and the result of direct Coomb's test was negative. The Kleihauer-Betke test revealed 5% of fetal erythrocytes in the maternal bloodstream equivalent to 180 mL. The fact that FMH can occur without prior risk factors, and the diagnosis is often postnatal, underscores the importance of heightened of medical suspicion particularly in infants born to immigrants where there is often the lack of prenatal visits.

Allogeneic blood transfusion decreases with postoperative autotransfusion in hip and knee arthroplasty.

OBJECTIVES: We aimed to evaluate the effectiveness of postoperative autotransfusion method on prevention of the need of allogeneic blood transfusion in hip and knee arthroplasty. METHODS: Seventy-four patients who underwent 77 hip and knee arthroplasty operations were randomized into control and study groups, and evaluated prospectively. In the knee group (39 patients; 30 females, 9 males; mean age 66.6 years), cemented, cruciate retaining, and bicompartmental arthroplasty was performed under tourniquet control; whereas in the hip group (35 patients; 24 females, 11 males; mean age 59.3 years) cementless arthroplasty with posterolateral approach was performed. None of the patients received preoperative and intraoperative allogeneic blood transfusion. The collected blood in the surgical area was transfused with autotransfusion system to the patients in the study groups at the end of the fourth hour postoperatively. The mean amounts of autotransfused blood in hip and knee groups were 413 mL and 480 mL, respectively. Allogeneic blood transfusion was applied to the patients with hemoglobin level below 8 g/dL, hematocrit level below 25%, and clinical symptoms of anemia. RESULTS: Preoperative and postoperative hemoglobin-hematocrit levels did not differ significantly between study and control groups. Allogeneic blood transfusion was applied to one patient (5%) in study and 8 patients (38%) in control groups during knee arthroplasty (p=0.01); whereas 9 patients (53%) in study and 15 patients (79%) in control groups received allogeneic blood transfusion during hip arthroplasty (p=0.044). The amount of allogeneic blood transfusion in study groups was significantly lower than that in control groups (p=0.008 for knee arthroplasty, p=0.048 for hip arthroplasty). CONCLUSION: The need and amount of allogeneic transfusion were reduced with postoperative autotransfusion in both knee and hip arthroplasty groups with greater extent in knee arthroplasty.

Pregnancy in beta-thalassemia trait carriers: an uneventful journey.

Normochromic normocytic anemia during pregnancy reflects the significant increase in plasma volume, which disproportionately exceeds the increase in the red cell volume. In beta-thalassemia (beta-thal) trait carriers who become pregnant the plasma volume expansion may cause more pronounced anemia because the anemia of pregnancy is added to the pre-existed hypochromic microcytic anemia. In beta-thal women, pregnancy outcome and obstetric complications do not differ from the general population. Anemia in beta-thal carriers is generally not severe enough to warrant anxiety. No specific therapy is indicated and pregnant women generally require only supportive care with an anticipated favorable pregnancy outcome.

[Diagnosis and therapy of renal anemia]. / A renalis anaemia diagnosztikája és terápiája.

The cardiovascular state and life quality of patients suffering from chronic renal insufficiency is primarily determined by their haemostatic status. Renal anemia can positively be diagnosed if the glomerular filtration rate diminishes significantly (<60 ml/min/1,73 m 2 ). Other causes of anemia besides renal insufficiency can be excluded in these instances. The primary aim of erythropoietin treatment is to abolish the transfusion demand of patients suffering from renal insufficiency as this could lead to antibody formation and the transduction of viral infections. In case the existence of renal anemia is proved, the target values must be determined. A target value of >11 g/dl hemoglobin should be achieved for at least 85% of the patients in order to get an average hemoglobin level of 12-12,5 g/dl for the whole patient population. During the treatment of renal anemia regulating the iron metabolism of patients is of primary importance. A >5% rate of the hypochromic red blood cells in the blood circulation implies iron deficiency; but a value above 10% positively indicates iron deficiency. The transferric saturation values under 20% indicate functional iron deficiency and this indicator is a good means of following iron treatment. In the case of patients receiving dialysis parenteral input is advised because of poor iron absorption. In national clinical practice several erythropoietin products are available (erythropoietin-alpha, erythropoietin-beta, alpha-darbepoetin and continuous erythropoietin receptor activator, a new product now being introduced). When selecting the appropriate treatment strategy for each patient, the application method, the effect range and cost efficiency of the selected erythropoietin product must be taken into consideration.

[The interpretation of carbon monoxide diffusing capacity test depending of hemoglobin concentration]. / Interpretacja badania zdolnosci dyfuzyjnej pluc w zaleinosci od stezenia hemoglobiny krwi.

UNLABELLED: The carbon monoxide diffusion capacity (DLCO) is among others dependent of the hemoglobin value. The result of DLCO test in patients with anemia change when we adjust DLCO for hemoglobin (Hb) concentration. The aim of the study was to estimate if the differences between result of DLCO and DLCO/VA before and after adjust the Hb value can change the interpretation of the test in the group with normal and low value of Hb. The study group consist of 25 patients with normal level of Hb (group A) and 21 ones with anemia (group B). All studied have been done spirometry, bodypletyzmografy and DLCO test. All tests were made on the SensorMedics. The DLCO test was made in the single breath diffusing capacity program Results. The values of the Hb in the group A were above 13 g/dl for female and 14 g/dl for man. In the group B the Hb value were less then 10 g/dl. In the group A the middle Hb concentration was 14,49 +/- 1,36g/dl. DLCO and DLCO/VA before and after Hb value adjusted were 91,4 +/-17,98 vs 90,7 +/- 17,58 % i 101,5 +/- 19,46 vs 100,7 +/- 18,65% (p>0,05). In the group B the middle Hb concentration was 8,77 +/- 0,97 g/dl. DLCO and DLCO/VA before and after Hb value adjusted were: 57,05+/-17,55 vs 72,19+/-25,27% i 67,57+/-11,18 vs 84,66+/-14,62% (p< 0,05). CONCLUSIONS: 1. The were non statistically important change in the DLCO test results after consideration on Hb level in the studied group without anemia, so in the patients with normal level of Hb the DLCO test result doesn't change the interpretation of the test after the consideration on Hb concentration 2. In patients with anemia we shout adjust the Hb value to the DLCO test because the results with out this can completely change the interpretation of the test and clinical diagnosis

Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q.

Deletions of the long (q) arm of chromosome 5 [del(5q)]occur in patients with myelodysplastic syndromes (MDS) including, but not limited to, those who meet the WHO definition of the 5q- syndrome. Del(5q) MDS patients frequently have symptomatic anemia, and its treatment has traditionally consisted of RBC transfusions and, for some, iron chelation therapy. Erythropoietin, darbepoetin, hypomethylating agents, and lenalidomide can enhance erythropoiesis in MDS patients with anemia, increasing hemoglobin levels and abrogating RBC transfusion requirements. Lenalidomide is particularly active in treating the anemia of del(5q) MDS, which is especially relevant given the low response rate to erythropoietin in this group of patients. In a recent study of 43 MDS patients, 10 of 12 patients (83%) with del(5q) MDS achieved sustained RBC transfusion independence (or a > 2 g/dL increase in hemoglobin), compared with 57% of those with a normal karyotype and 12% of those with other karyotypic abnormalities. Complete cytogenetic remissions were achieved in 75% (nine of 12) of the del(5q) MDS patients, suggesting that lenalidomide targets a fundamental pathogenetic feature of MDS that is more pronounced in the presence of chromosomal 5q deletions. This review highlights some issues about the classification and treatment of del(5q) MDS.