Recommendations regarding splenectomy in hereditary hemolytic anemias.

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children.

Microfluidic study of enhanced deposition of sickle cells at acute corners.

Sickle cell anemia is a blood disorder, known to affect the microcirculation and is characterized by painful vaso-occlusive crises in deep tissues. During the last three decades, many scenarios based on the enhanced adhesive properties of the membrane of sickle red blood cells have been proposed, all related to a final decrease in vessels lumen by cells accumulation on the vascular walls. Up to now, none of these scenarios considered the possible role played by the geometry of the flow on deposition. The question of the exact locations of occlusive events at the microcirculatory scale remains open. Here, using microfluidic devices where both geometry and oxygen levels can be controlled, we show that the flow of a suspension of sickle red blood cells around an acute corner of a triangular pillar or of a bifurcation, leads to the enhanced deposition and aggregation of cells. Thanks to our devices, we follow the growth of these aggregates in time and show that their length does not depend on oxygenation levels; instead, we find that their morphology changes dramatically to filamentous structures when using autologous plasma as a suspending fluid. We finally discuss the possible role played by such aggregates in vaso-occlusive events.

A new high affinity variant Hb Aurillac (ß141Leu→Val).

Hemoglobin (Hb) variant ß141(H19)Leu→Val (HBB:c.424C>G), one of the two mutations defining Hb Kochi [the other one being ß144(HC1)Lys-Tyr-His→0 (HBB:c.433A>T)], was found as an isolated mutation. In contrast to what was suggested for Hb Kochi, the new variant was not clinically silent. It displayed increased oxygen affinity and was associated with mild erythrocytosis.

Recommendations for Pregnancy in Rare Inherited Anemias.

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders.

[Hereditary hemochromatosis, the clinician point of view]. / L'hémochromatose génétique, le point de vue du clinicien.

Hereditary hemochromatosis (HH) is an autosomal recessive disease whose most common form is due to homozygosity for the C282Y mutation of the HFE gene. Its prevalence is estimated between 1/200 and 1/600 in France. This represents potentially several thousands of affected people. The disease is characterized by progressive iron overload, which can lead to irreversible parenchymal tissue damage. When clinical signs become evocative the disease is already at an advanced stage and years of life are probably lost. It is therefore important to detect the disease early. The clinician, either general practitioner or specialist, plays a pivotal role in the diagnostic process: he/she receives complaints of patients, prescribes complementary investigations, conducts the treatment and must organize of the family screening. Based on the French recommendations and on literature data, this paper presents the main lines of management of the patient as responses to the eight following questions: 1) Under what circumstances should the clinician suspect HH? 2) How to conduct investigations in the presence of high ferritin levels? 3) What manifestations must be feared with the worsening of iron overload? 4) What medical evaluation should be performed when the diagnosis of HH has been made? 5) How to conduct iron depletive treatment in practice? 6) How to monitor the treated patient? 7) What is the place of iron-chelating drugs in the treatment of HH? 8) How to take charge of the family members?

Rapid detection of beta-Thalassemia alleles in Egypt using naturally or amplified created restriction sites and direct sequencing: a step in disease control.

beta-Thalassemia (thal), the most common genetic disorder in Egypt, is a major health problem with an estimated carrier rate of 9-10%. This study, aimed at describing the beta-globin gene mutations in the Suez Canal area, an important Egyptian region, to provide a foundation for a disease control program. We studied 44 beta-thalassemic patients (and their relatives) from 35 families living in this region. The commonest mutations were genetically diagnosed using naturally or amplified created restriction sites. Less frequent mutations were characterized by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. Twelve different mutations were identified in 51 unrelated chromosomes. The three most frequent mutations were IVS-I-110 (G-->A), IVS-I-1 (G-->A) and IVS-I-6 (T-->C). The spectrum of rarer mutations was heterogeneous and differed from that reported in other areas of Egypt. We also identified the first homozygous case of a rare mutation, codon 24 (-G; +CAC), displaying a thalassemia major phenotype. Parental consanguinity was high (60.6%) with 35.7% of the compound heterozygous patients having consanguineous parents. These data provide insights for the distribution of beta-thal alleles in this region, and could be used as a basis for genetic counseling and prenatal diagnosis.