Generation of a Core Set of Items to Develop Classification Criteria for Scleroderma Renal Crisis Using Consensus Methodology.

OBJECTIVE: To generate a core set of items to develop classification criteria for scleroderma renal crisis (SRC) using consensus methodology. METHODS: An international, multidisciplinary panel of experts was invited to participate in a 3-round Delphi exercise developed using a survey based on items identified by a scoping review. In round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In round 2, participants were asked to rate the validity and feasibility of the items using Likert-type scales ranging from 1 to 9 (where 1 = very invalid/unfeasible, 5 = uncertain, and 9 = very valid/feasible). In round 3, participants reviewed the results and comments from round 2 and were asked to provide final ratings. Items rated as highly valid and feasible (median scores ≥7 for each) in round 3 were selected as the provisional core set of items. A consensus meeting using a nominal group technique was conducted to further reduce the core set of items. RESULTS: Ninety-nine experts from 16 countries participated in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13, in the categories hypertension, renal insufficiency, proteinuria, and hemolysis. Eleven experts took part in the nominal group technique discussion, where consensus was achieved in 5 domains: blood pressure, acute kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and renal histopathology. CONCLUSION: A core set of items that characterize SRC was identified using consensus methodology. This core set will be used in future data-driven phases of this project to develop classification criteria for SRC.

Updated clinical classification of pulmonary hypertension.

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (PPHN) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1. Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4.

Hemolytic non-uremic syndrome.

We describe three children who developed isolated but severe microangiopathic hemolytic anemia without other manifestations of hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). All three recovered without specific treatment. We propose that they represent a unique phenotype in the spectrum of TTP and HUS, which we term "hemolytic non-uremic syndrome."

Glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community.

Experience with eosin-5'-maleimide as a diagnostic tool for red cell membrane cytoskeleton disorders.

The diagnosis of hereditary spherocytosis (HS) is based on red cell morphology and other conventional tests such as osmotic fragility, autohemolysis and acidified glycerol lysis. However, milder cases are at times difficult to diagnose. Confirmation by red blood cell (RBC) membrane protein analysis is not possible in most laboratories. Recently, a flow cytometric method has been described for quantitating the fluorescence intensity of intact red cells after incubation with the dye eosin-5'-maleimide (EMA), which binds specifically to the anion transport protein (band-3) at lysine-430. This has been shown to be an effective screening test for red cell membrane disorders. We evaluated the usefulness of this approach for screening membrane protein disorders such as HS and hereditary elliptocytosis (HE) and its value in discriminating this group from other hemolytic anemias, such as glucose-6-phosphate dehydrogenase (G6PD) deficiency, beta-thalassemia trait, sickle cell anemia and autoimmune hemolytic anemia. Fluorescence intensity, expressed in mean channel fluorescence (MCF) units, was determined using a Becton Dickinson FACS Caliber flow cytometer. Membrane protein analysis was carried out by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis (SDS-PAGE). RBCs from patients with HS and HE gave significantly lower MCF values (P < 0.001) than the normal control group and other patient groups. The diagnosis of HS in four cases was confirmed by RBC membrane protein electrophoresis and all showed a deficiency of spectrin. The advantage of the EMA dye method are its specificity for membrane disorders, as well as being a simple, user-friendly and rapid method which is inexpensive, provided a flow cytometer is available.

Crises falciformes / Sickle cell crisis

Foi feita a revisão das complicações agudas da doença falciforme, ou crises, com sugestões de condutas, baseadas na literatura

Runner's anemia.

Macrocytic anemia occurring in patients with fatigue suggests numerous diagnoses, ranging from nutritional deficiencies to a myelodysplastic syndrome. A careful history-taking is critically important for recognition of runner's anemia, which is due to plasma volume expansion, with hemolysis from the pounding of feet on pavement, and hemoglobinuria. Gastrointestinal blood loss may also contribute to anemia in long-distance runners. Early recognition of runner's anemia in patients with a complex presentation of anemia is important in circumventing many diagnostic tests. Runner's anemia should be considered when, amidst a constellation of signs and symptoms, mild anemia is well tolerated by an avid runner.

[Classification and diagnosis of hemolytic anemias].

Hemolysis is characterized by shortening of the red cell life span. When the red cell destruction exceeds the ability of the marrow to increase red cell production to compensate for, hemolytic anemias develop. These conditions are subdivided into hereditary abnormalities and acquired abnormalities. Except for PNH, all types of hemolytic anemia due to intrinsic abnormalities are inherited and those of extrinsic ones are acquired. Extrinsic factors include antibodies, physical trauma, biological agents, chemical agents and physical agents. For determining the specific cause of the conditions, anti-globulin test, morphological observation, analysis of hemoglobin, red cell enzyme assay, screening tests for PNH are needed.

Hemolytic anemias due to disorders of red cell membrane skeleton.

During the past 10 years, knowledge of the composition, function and supramolecular assembly of the red cell membrane has been greatly expanded by progress in molecular and cell biology. Detailed information on the organization of membrane cytoskeletal proteins and their molecular characterization has allowed us to correlate a number of protein abnormalities with clinical symptoms that are peculiar to hereditary hemolytic anemias (HHA). In particular, three general principles emerge that can help us to understand the pathogenetic mechanisms of HHA: (a) protein-protein and protein-lipid interactions greatly influence the correct assembly of the membrane skeleton; (b) the red blood cell (RBC) membrane skeleton mostly determines the shape (discocyte), deformability (rheologic properties) and durability (half-life and resistence to shear stress) of the erythrocytes; (c) changes in cytoskeletal composition and/or organization can produce alterations in all of the above properties, and therefore they are responsible for the onset of the hemolytic damage.

Hemolytic anemias in pregnancy.

Polymorphism exists and complicates the diagnosis of inherited hemolytic anemias. However, with linkage DNA analysis and, on occasion, with characterization of the mutant gene, it is possible to make a diagnosis on the DNA level. This technique increases our understanding of the enzymatic defect and the relationship with clinical findings. In acquired hemolytic anemias, pregnancy is one of the most commonly associated conditions. The physiology is not yet entirely understood and, therefore, does not allow specific treatment. Supportive therapy is usually the rule in these cases.