[Current management of thalassemia intermedia]. / Prise en charge actuelle des thalassémies intermédiaires.

Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Non-transfusion-dependent thalassemia encompasses 3 main clinical forms: beta-thalassemia intermedia, hemoglobin E/beta-thalassemia and alpha-thalassemia intermedia (HbH disease). Clinical severity of thalassemia intermedia increases with age, with more severe anemia and more frequent complications such as extramedullary hematopoiesis and iron overload mainly related to increased intestinal absorption. Numerous adverse events including pulmonary hypertension and hypercoagulability have been associated with splenectomy, often performed in thalassemia intermedia patients. The potential preventive benefit of transfusion and chelation therapies on the occurrence of numerous complications supports the strategy of an earlier therapeutic intervention. Increasing knowledge about pathophysiological mechanisms involved in thalassemia erythropoiesis and related iron overload is currently translating in novel therapeutic approaches.

Hemolytic transfusion reaction due to anti-IH.

BACKGROUND: Anti-IH is usually a clinically insignificant antibody that may complicate a serologic workup. However, it can occasionally cause hemolysis. We report a rare case of acute hemolysis caused by anti-IH. CASE REPORT: A 60-year-old man with a long history of chronic myelomonocytic leukemia and anemia, blood group A, D+ was found to have an unidentified antibody on serologic workup. He received an A, D+ red blood cell (RBC) unit that was crossmatch compatible by immunoglobulin G indirect antiglobulin test and then experienced an acute hemolytic transfusion reaction with fever, hemoglobinuria, and acute renal failure. The antibody was later identified as an anti-IH with a wide thermal amplitude. The transfused RBCs were later typed as A(2). The patient was subsequently typed as an A(1) individual. The patient recovered completely from the effects of this reaction and was transfused with A(1) RBCs over the next few days with no adverse effect. CONCLUSION: Anti-IH, which is usually clinically insignificant and often found in A(1), B, and A(1) B individuals, can, on rare occasions, cause acute hemolytic transfusion reactions, especially when an A(2) unit is transfused to an A(1) patient.

Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer.

PURPOSE: Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis. METHODS: Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival. RESULTS: Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (P(trend) < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk. CONCLUSION: Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted.

Lowered antioxidant status of red blood cells in post-parturient haemoglobinuria of buffaloes.

The antioxidant status of the red blood cells of buffaloes (n = 20) suffering from post-parturient haemoglobinuria (PPH) was assessed by comparing their tocopherol (vitamin E) and reduced glutathione contents with those of red blood cells from apparently healthy buffaloes (n = 20). The red cell tocopherol content of the diseased buffaloes (1.76 +/- 0.11 micrograms/ml) was significantly (p < 0.01) lower than that of healthy buffaloes (2.45 +/- 0.14 micrograms/ml). This may be the first report comparing the concentration of tocopherol in the red blood cells of buffaloes suffering from PPH and apparently healthy buffaloes. There was a drastic reduction in the reduced glutathione content in the red cells of haemoglobinuric buffaloes (23.74 +/- 2.86 mg%) compared to the healthy control buffaloes (73.71 +/- 3.87 mg%). The diseased buffaloes also exhibited severe hypophosphataemia. These findings suggest that an impaired or insufficient antioxidant potential of the red blood cells in this disease in buffaloes is associated with the phosphorus deficiency.

Variation of serum inorganic phosphorus and association with haemoglobinuria and osteomalacia in female water buffaloes in Pakistan.

Data from an animal health service in the Punjab of Pakistan showed that 39 adult female buffaloes with haemoglobinuria were 21 times more likely to have serum inorganic phosphorus (serum P) levels < 0.97 mmol/l than 24 controls sampled during the period of case occurrence (December 1984-March 1985). Age > 7 years or early lactation (1-60 days post partum) were unrelated to the disease. Similarly, symptoms of osteomalacia in 19 multiparous buffaloes were associated with low P (OR = 14.3) but not with age. Subsequently, a serum survey was carried out from February 1985 to July 1987 to investigate serum P variations with season and host factors. Data from 139 farms (426 adult female buffaloes, 468 lactations) indicated strong farm and seasonal effects on serum P. Serum P declined during the study period and was lowest during December-March 1985/1986 and again 1986/1987. Calving season, parity > 1, high pregnancy > 6 months, or daily milk production were not related to serum P in the final model. Seasonal effects were interpreted as soil borne and related to feed changes from maize to berseem in December.

The effect of erythroid hyperplasia on iron balance.

Measurements of erythropoiesis and iron balance were made in eight normal and 32 anemic subjects. The latter consisted of 12 individuals with ineffective erythropoiesis (beta-thalassemia/hemoglobin E), 13 subjects with ineffective erythropoiesis and hemolytic anemia (hemoglobin H), and seven subjects with hemolytic anemia (hereditary spherocytosis). A consistent relationship within each group existed between the degree of erythropoiesis and radioiron absorption. Although the effect of erythropoiesis on iron absorption was of similar magnitude in the two thalassemia groups, the effect in hereditary spherocytosis was much less. There was agreement between absorption and ferritin or magnetic susceptibility (SQUID) measurements of iron stores in thalassemia, but in hereditary spherocytosis a discrepancy existed between absorption and ferritin. It is concluded that, although increased erythropoiesis is associated with increased iron absorption, some additional factor associated with red cell breakdown is more directly responsible for the positive iron balance in thalassemia.

Bovine postparturient hemoglobinemia: hypophosphatemia and metabolic disorder in red blood cells.

Mechanism of hemolysis in postparturient hemoglobinemia was studied in 7 cows. Cows 1 to 5 had a history of hemoglobinemia at a previous calving, but hemoglobinemia did not occur during the present parturition. Cow 6, a daughter of cow 4, and cow 7 from another farm, developed postparturient hemoglobinemia and had hemoglobinuria on days 20 and 21 and 10 to 17 after calving, respectively. During the time cows 6 and 7 had hemoglobinuria, both cows had a marked decrease in serum inorganic phosphorus, RBC adenosine 5'-triphosphate (ATP), and reduced glutathione, and a significant (P less than 0.01) increase in methemoglobin concentration. In cow 6, these changes were observed before the onset of hemoglobinuria, indicating metabolic disorder of RBC. After phosphate administration IV, serum inorganic phosphorus was corrected, and RBC ATP was increased above base-line value. During the time cows 6 and 7 had hemoglobinuria, PCV, hemoglobin concentration, and RBC count decreased progressively and reached nadir values, 40% to 50% of baseline values, on day 22 in cow 6 and on day 19 in cow 7. Cows 6 and 7 were anemic, even after serum inorganic phosphorus and RBC ATP values returned to acceptable values. Glycolytic disorder and depletion of ATP, resulting from phosphorus deficiency, appeared to be a primary and essential step leading to hemolysis in postparturient hemoglobinemia in cows 6 and 7.

Bovine post-parturient haemoglobinuria: effect of inorganic phosphate on red cell metabolism.

Washed red blood cells from normal cows were incubated as 10 and 20 per cent suspensions in media containing 0, 2.5 and 25 mM phosphate. The results showed that the rate of glycolysis was dependent on the inorganic phosphate concentration. In the absence of phosphate, the consumption of glucose and the production of 2,3-diphosphoglycerate, lactate and adenosine 5'-triphosphate (ATP) were decreased. Incubation without added phosphate also greatly increased the production of fructose-1,6-diphosphate, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Moderate hypophosphataemia was induced in two pre-ruminant calves. Washed red cells from the blood of these animals showed a depletion of ATP when compared with red cells from a control calf. The results indicate that phosphorus deficiency, leading to hypophosphataemia, may be a mechanism of post parturient and related syndromes of haemoglobinuria by decreasing red cell glycolysis and resultant ATP synthesis. Subnormal concentrations of ATP would predispose red cells to altered structure and function, a loss of normal deformability, and an increase in fragility and haemolysis with resultant haemoglobinuria.

Double heterozygosis for hemoglobin C-beta thalassemia: description of a Spanish family. Hemoglobin C-beta thalassemia in a Spanish family.

A spanish family is described with two abnormal genes: 1) hemoglobin C in heterozygosis with normal hemoglobin, introduced by the subject's mother, and 2) heterozygotic betathalassemia for which the father is a carrier. In the subject and his sister, both abnormal genes coincide with the presence of hemoglobin C and hemoglobin F, simulating homozygosis for hemoglobin C. The clinical condition shows medium intensity chronic hemolysis. In the subject's brother, mother and grandmother, simple heterozygosis of hemoglobins A-C is seen, with no apparent clinical manifestations. The father shows subjaundice with some acute hemolytic episodes. Hypotheses are discussed which might explain the presence of these hemoglobins in Spain.

Extraction of erythrocyte membrane proteins by sulfhydryl inhibitors.

Human red cell membrane proteins were extracted by incubation of the ghost with hypotonic phosphate buffer (pH 7.4), N-ethylmaleimide and p-hydroxy-mercuribenzoate. In paroxysmal nocturnal hemoglobinuria (PNH), hereditary spherocytosis (HS) and hereditary elliptocytosis, the amount of proteins extracted by these procedures was significantly less than the amount extractable from the ghost of normal and aplastic anemia red cells. Polypeptide patterns of red cell membranes in these hematological disorders were essentially similar to those of normal ghosts. Analysis of the supernatant by SDS polyacrylamide gel electrophoresis revealed that this reduction was mainly due to the reduced amount of peripheral proteins extracted. The extraction of peripheral proteins by sulfhydryl reagents was accompanied by shape changes resulting in the formation of membrane vesicles, suggesting an important role of peripheral proteins in the maintenance of ghost shape. It is also suggested that qualitative abnormalities of peripheral proteins such as altered reactivity to sulfhydryl reagents and/or strong binding to the membrane are present in PNH, HS and hereditary elliptocytosis red cells.