[Treatment of iron deficiency anemia during pregnancy with oral iron: State of practice among midwives]. / Traitement par fer oral de l'anémie ferriprive lors de la grossesse : état des pratiques chez les sages-femmes.

OBJECTIVES: Iron deficiency anemia represents a public health issue which is usually managed by midwives. Because it is associated with maternal and fetal risks, a treatment is warranted. Oral iron represents the main option for treating this condition. Despite the existence of national and international guidelines no consensus about its modality of use has emerged so far. The primary objective of this study was to analyze midwives'practice with regards to iron deficiency anemia treatment using oral iron formulations. METHODS: We conducted an observational and descriptive cross-sectional in a sample of midwives from the Gironde administrative region using a questionnaire. RESULTS: We obtained 85 questionnaires from midwives working in private or public health facilities. Doses of iron and duration of treatment seem insufficient for a majority of responders. Folic acid and vitamin C are often associated with oral iron. Most midwives assess the efficacy of oral iron at one month with hemoglobin and ferritin levels. A significant fraction of these midwives shares similar practices which are in good accordance with the literature such as patient counselling with regards to drug intake, management of gastrointestinal side effects and inefficacity of oral iron. Noticeably, some of these midwives don't follow any guidelines. CONCLUSION: The majority of participants demonstrated practices in accordance with various national guidelines although no precise therapeutic algorithm is available as reference. Larger studies on the management of iron deficiency anemia in pregnancy by health professionals and harmonization of practices are necessary.

Transfusional iron overload in patients with myelodysplastic syndromes: A 10-year retrospective survey from a French general hospital.

We retrospectively assessed the characteristics of 165 MDS patients from our institution having received at least 20 RBC units. In the vast majority of them various comorbidities (range: 1-6 per patient) were registered including mainly cardiovascular disorders. Serum ferritin was over 1000µg/L in about half of tested individuals. A chelator agent was initiated in 43.6% of patients (mainly low-risk MDS). Transformation in AML occurred in 46 cases (27.8%). Overall, 112 patients died during follow up. The cause of death was documented in 65 cases and included mainly MDS or AML resistance to therapy. There was a context of bacterial or fungal-related sepsis in 35.3% of cases. We noticed a correlation between survival and number of RBC transfusions. Median OS from the 20th RBC unit was significantly prolonged among the chelated subgroup. Consequences of transfusional iron overload and chelation need to be clarified in MDS patients.

When genetic and surname analyses meet historical sources: The C56R mutation associated with factor XI deficiency as a marker of human migration during the Spanish Reconquista.

The C56R mutation associated with factor XI deficiency has been first evidenced in individuals from the French Basque Country. Genetic investigations revealed that this mutation occurred about 5400 years ago as a founder effect in this zone. Other cases were subsequently described in Southwestern Europe. Noticeably a cluster of cases was evidenced in Yecla, a small city from the province of Murcia, in Southeastern Spain. In correlation with historical sources our genetic data and surname analysis argue for associating this mutation with the migration of people from Western Pyrenees (and more probably from the Navarra province) toward Southeastern Spain during the Reconquista period.

[How to reduce rapidly destruction of labile blood components at the health facilities level? The experience of Centre Hospitalier de la Côte Basque]. / Comment réduire rapidement la destruction des produits sanguins labiles à l'échelle d'un établissement de santé ? L'expérience du centre hospitalier de la Côte Basque.

OBJECTIVE: The destruction of labile blood components (LBC) is of major concern. The objective was to carry out actions aiming to rapidly reduce this rate and to evaluate results in a single institution. METHODS: From 2017 we developed in the Centre Hospitalier de la Côte Basque a strategy in order to struggle against this problem including: 1/general information of prescriptors for reducing LBC waste, 2/fractioned delivery of RBC unit per unit, 3/recommendations to nurses, 4/information on platelets reserve, 5/new policy for ambulances and emergency unit: transfusion emergency package conditioned in single RBC units including a temperature recorder. Following the implementation of these measures, we analyzed the evolution of waste regarding number and distribution of causes. RESULTS: In contrast to stability of LBC destructions during these recent years between 0.84 and 0.97% we observed a marked decrease in 2017 (0.56%) and the first six months of 2018 (0.28%). Considering the evolution of causes between 2016 and 2017 we noticed for instance a disappearance of destructions due to patient' refusal and out of time of expiry or at level of the mobile emergency unit. Of note reduction of destruction is marked in the three categories of LBC. However, there still remains a large room for improvement regarding avoidable causes of destruction. CONCLUSION: It is possible to reduce very rapidly and significantly the fraction of LBC destruction in a health facility thanks to measures including information, teaching, organization and material conducted both in the blood bank and in clinical departments.

Evidence of an ancient (2000 years ago) goiter attributed to iodine deficiency in North America.

The Adena pipe figurine was found in the 2000 year-old Adena burial mound in Ross County, Ohio, USA by William C. Mills in 1901. The pipe reportedly represents an achondroplastic dwarf male Native American. However, the clinical aspect (swelling of the neck), the environmental/cultural characteristics in this area (iodine-poor soils, absence of seafood and milk consumption, tobacco smoking), and the marked prevalence of goiter among Native American populations favor the diagnosis of a goiter associated to iodine deficiency. Similar indigenous art representations found in South America and Mesoamerica strengthen this hypothesis. To our knowledge the Adena pipe is the first example of goiter depicted in Native North American art and one of the oldest from the continent.

[Evolutionary medicine: A new look on health and disease]. / La médecine évolutionniste : un nouveau regard sur la santé et les maladies.

Evolutionary medicine represents an innovative approach deriving from evolutionary biology. It includes the initial Darwin's view, its actualization in the light of progresses in genetics and also dissident theories (i.e. non gene-based) particularly epigenetics. This approach enables us to reconsider the pathophysiology of numerous diseases, as for instance, infection, and our so-called diseases of civilization especially obesity, type 2 diabetes, allergy or cancer. Evolutionary medicine may also improve our knowledge regarding inter-individual variation in susceptibility to disease or drugs. Furthermore, it points out the impact of our behaviors and environment on the genesis of a series of diseases.

C282Y/H63D hemochromatosis mutations and microevolution: Speculations concerning the Basque population.

The Basques live at the Western extremity of the Pyrenees. According to linguistic and genetic data they could be considered as one of the most ancient European populations. Numerous studies have evidenced particular patterns in the frequency of several genetic polymorphisms in this relatively unmixed human group. We discuss herein the puzzling distribution of the two major hemochromatosis HFE mutations associated with hereditary hemochromatosis. Thus, one can observe a low frequency of C282Y and, in contrast, one of the highest European frequencies of H63D. Genetic drift (enhanced by the long history and the small size of this population), long persistence of Paleolithic iron-rich diet, lower exposure to major infectious threats and limited mixing with both Celts and Vikings (who demonstrate the highest prevalence of C282Y) could be the underlying factors explaining these particular genetic features. Historical and environmental data represent key elements for understanding the role of the different evolutionary forces which shape the genetic profile of human populations.

Factor XI replacement for inherited factor XI deficiency in routine clinical practice: results of the HEMOLEVEN prospective 3-year postmarketing study.

Factor XI (FXI)-deficient patients may develop excessive bleeding after trauma or surgery. Replacement therapy should be considered in high-risk situations, especially when FXI levels are below 20 IU dL(-1) . HEMOLEVEN is a human plasma-derived factor XI concentrate available in France since 1992, but there are few data regarding its use by physicians. This prospective study assessed the use, efficacy and safety of HEMOLEVEN in common clinical practice. HEMOLEVEN was evaluated in FXI-deficient patients in 13 French centres in a 3-year postmarketing study. Forty-four patients (30 females, 14 males) received 67 treatments. The median age was 37 years (8 months-91 years). Basal FXI levels were <1 to 51 IU dL(-1) (median: 5.5); 29 patients were severely FXI-deficient (<20 IU dL(-1) ). FXI was administered prophylactically before 43 surgical procedures, 10 invasive procedures, 8 vaginal deliveries, or as curative treatment for six bleeds. The efficacy was assessed as excellent/good in 63, moderate in two and undetermined in two treatments. Seven patients experienced seven adverse effects, including two rated as serious: one sudden massive pulmonary embolism with fatal outcome and one case of inhibitor to FXI. HEMOLEVEN is effective for bleeding prevention in FXI deficiency. However, considering the benefit/risk ratio observed in relation to dosage in this study; firstly, it should be used sparingly due to its potential prothrombotic effect; secondly, new prescription procedures should be defined to adapt the dosage, especially in patients with intrinsic and/or acquired risk factors for thrombosis.

Why is factor V Leiden so rare in the Basques?

Factor V Leiden is the most common inherited trait in Caucasians that predisposes individuals to venous thrombosis. However, it is almost absent amongst the Basque people that live in the south western part of Europe. To explain this finding, we speculate upon the putative contribution of various evolutionary forces through which the Basque genome may have been shaped.

[The relationship between aneurysmal subarachnoid hemorrhage and meteorological parameters based on a series of 236 French patients]. / Relations entre hémorragies sous-arachnoïdiennes par rupture anévrysmale et paramètres météorologiques à partir d'une série française de 236 patients.

Subarachnoid hemorrhage (SAH) is a sudden and potentially severe event with mortality rates ranging between 24 and 30 % depending on the initial clinical condition. Studies have attempted to assess the possible influence of meteorological parameters on the occurrence of SAH. However, this idea remains very controversial and the results vary widely from one study to another. Our study is the second largest French series, and first performed in a homogeneous series of patients. The aim of our study was to attempt to establish a relationship between the weather (i.e.) temperature variations and daily variations of atmospheric pressure in the days before the onset of SAH and the same day and the occurrence of non-traumatic SAH in a homogeneous population of 236 patients from a single center, over a period of 7 years (2002 to 2008). This retrospective study does not suggest any relationship between the occurrence of SAH and meteorological data studied. Moreover, no relationship was observed between mean changes in temperature or pressure and the occurrence of SAH, that the day of the bleeding or the days preceding the SAH. However, a female predominance was observed and a relatively high mortality rate of 18.3 %. The distribution of the occurrence of an SAH was random. As it seems impossible to provide logistics and organization of care for non-traumatic SAH, the care system must remain vigilant throughout the year.

Point mutations regarded as missense mutations cause splicing defects in the factor XI gene.

BACKGROUND: Point mutations within exons are frequently defined as missense mutations. In the factor (F)XI gene, three point mutations, c.616C>T in exon 7, c.1060G>A in exon 10 and c.1693G>A in exon 14 were reported as missense mutations P188S, G336R and E547K, respectively, according to their exonic positions. Surprisingly, expression of the three mutations in cells yielded substantially higher FXI antigen levels than was expected from the plasma of patients bearing these mutations. OBJECTIVES: To test the possibility that the three mutations, albeit their positions within exons, cause splicing defects. METHODS AND RESULTS: Platelet mRNA analysis of a heterozygous patient revealed that the c.1693A mutation caused aberrant splicing. Platelet mRNA of a second compound heterozygote for c.616T and c.1060A mutations was undetectable suggesting its degradation. Cells transfected with a c.616T minigene favored production of an aberrantly spliced mRNA that skips exon 7. Cells transfected with a mutated minigene spanning exons 8-10 exhibited a significant decrease in the amount of normally spliced mRNA. In silico analysis revealed that the three mutations are located within sequences of exonic splicing enhancers (ESEs) that bind special proteins and are potentially important for correct splicing. Compensatory mutations created near the natural mutations corrected the putative function of ESEs thereby restoring normal splicing of exons 7 and 10. CONCLUSIONS: The present findings define a new mechanism of mutations in F11 and underscore the need to perform expression studies and mRNA analysis of point mutations before stating that they are missense mutations.

Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes? A report on 59 cases.

Erythropoiesis-stimulating agents (ESAs) remain the first-line treatment of anemia in lower risk myelodysplastic syndromes (MDS) without 5q deletion. A preliminary report suggested that adding all-trans retinoic acid (ATRA) to ESAs may improve their erythroid response, particularly in patients with high endogenous erythropoietin (EPO) level, and may improve other cytopenias. We conducted a prospective multicenter study of EPO-beta and ATRA in anemic MDS patients with marrow blasts <10% and either previous ESA failure or relapse, endogenous EPO >500 U/l or other cytopenia(s) (absolute neutrophilic count <1.0 G/l or platelets <50 G/l). A total of 59 patients were evaluable after 12 weeks of treatment. The erythroid response rates according to IWG 2000 and 2006 criteria, respectively, were as follows: overall: 49 and 36%; patients with previous ESA failure (n=28): 43 and 32%; patients with endogenous EPO >500 U/l (n=18): 11 and 19%; patients transfused >2 red blood cells units/month (n=28) 43 and 39%. Only one neutrophil, but no platelet response, and no major side effect were observed. EPO-beta-ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia.

Factor V Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase 677T, and population genetics.

Thrombosis results from the interaction between predisposing genetic polymorphisms and acquired risk factors. Two of the main prothrombotic alleles, Factor V (FV) Leiden and prothrombin 20210A, are only encountered among European populations. They are estimated to have arisen about 21,000-34,000 years ago as founding mutations after the evolutionary divergence of Caucasians from Asians, and have been subsequently dispersed by the Neolithic migrations. These polymorphisms may have developed by means of genetic drift or natural selection by possibly conferring a reduced risk of bleeding. Of note, FV Leiden is nearly absent in the Basques, a European population of pre-Neolithic individualization. The C677T mutation of the methylenetetrahydrofolate reductase gene may induce hyperhomocysteinemia and could slightly increase the risk of arterial or venous thrombosis and pregnancy loss in individuals with folic acid deficiency. Through a selective phenomenon, the frequency of the mutation may parallel the intake of this vitamin within populations. Hence, this allele is underrepresented in Sub-Saharan Africa, Indonesia, and in the Inuits and a positive North to South gradient has been described in Europe. Thus, these three inherited prothrombotic polymorphisms represent interesting tools for population genetics studies.

Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis patients from the French Basque Country.

The distribution of HFE mutations was studied in patients from the French Basque Country with hereditary hemochromatosis (HH). The C282Y mutation was underrepresented but H63D seemed to demonstrate the highest prevalence when compared with other European countries. In addition, symptomatic HH was rarer in autochthonous Basques. This profile is interesting to consider in view of population genetics and should be associated with the search for non-HFE mutations.

Is the assessment of von Willebrand disease prevalence an achievable challenge? The example of the French Basque Country where blood group O and factor XI deficiency are highly prevalent.

The diagnosis of type I von Willebrand disease (VWD) is not straightforward because of the absence of a single clear-cut biological criteria and the interference of several acquired conditions on phenotype expression. We illustrate here this challenge with the French Basque population characterised by a marked high frequency in both blood group O and factor XI deficiency. From this example one may question the validity of epidemiological studies reporting on VWD prevalence.

Is there a 'Basque' profile regarding autosomal recessive deficiencies of coagulation factors?

When excluding haemophilia and von Willebrand disease, coagulation factors deficiencies constitute rare autosomal recessive disorders (<1 in 500,000) of less precisely defined epidemiology. We have reported herein the distribution of these entities in the French Basque Country, a genetic isolate of very old individualization with peculiar biological specificities. The prevalence of these disorders was markedly high, especially, as already shown, factor XI deficiency. This unusual profile needs to be discussed in the view of population genetics.