Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program.

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.

The clinical significance of magnesium depletion in thalassemia.

(1) Mg depletion in a population of 14 patients with thalassemia was documented by low serum Mg levels, abnormal Mg tolerance tests, and/or symptoms responsive to Mg therapy. (2) The observation that some degree of Mg depletion was present even in younger asymptomatic patients needs further investigation and suggests that monitoring of Mg status should be included in the routine care of patients with thalassemia. (3) Careful consideration should be given to the possibility that in patients with thalassemia early continuous supplementation with Mg is needed and may have a beneficial influence on the heart's response to chronic Fe overload and chronic hypoxemia.

Combined subcutaneous and high-dose intravenous deferoxamine therapy of thalassemia.

Although the preliminary findings are encouraging, to assess the effectiveness of the SHYD program on the long-term course of thalassemia, a larger patient population and longer treatment and follow-up period are needed. The presence of cardiac abnormalities in patients in Group I suggests that to prevent heart damage in thalassemia, it may be necessary to start the HTP and effective chelation therapy at a very young age, realizing that the amount of iron removed will be small. The finding that two of the four patients who survived to receive the largest amount of Fe/kg have intact spleens and another had splenectomy at age 24 suggests that, in these patients, the spleen may have had a protective role for the heart. If this observation is confirmed, it would provide evidence that removal of the spleen may adversely affect the long-term course of patients with thalassemia. Six years' experience with the SHYD program has not provided evidence for significant acute or chronic toxicity. This suggests that it might be safe to administer the i.v. treatments at home, a program that is anticipated for the future, as it would significantly reduce cost and possibly be more convenient.

Endocrine abnormalities in thalassemia major.

Endocrine function evaluations in 16 patients with beta-thalassemia indicate that hypogonadotropic hypogonadism, hypoparathyroidism, and reduced adrenocorticotropic hormone reserve occur frequently, whereas reduced growth hormone and thyroid reserve are less common manifestations. Hemosiderosis-induced damage of the endocrine glands seems to be the main cause for endocrine dysfunction in the patients studied.

Mineral balance (iron, aluminum, copper, zinc) after high-dose intravenous Desferal in a child with hemoglobin Hammersmith and Turner's syndrome.

A 12-day balance study with measurements of urine and stool excretion was undertaken to determine the effects of intravenous (i.v.) Desferal (293 mg/kg/24 h x 2) on iron, aluminum, copper, and zinc in a child with Hemoglobin Hammersmith and Turner's syndrome treated as a thalassemia major patient because of symptoms of anemia and ineffective erythropoiesis. Iron balance was positive, 34 mg/3 days baseline. The Desferal infusion induced iron excretion of 117 mg over 48 h, almost equally in stool and urine. This child receives approximately 20 transfusion/i.v. Desferal treatments yearly. If iron excretion is roughly the same with each treatment, it would equal 2,340 mg or 47% of her annual iron intake from transfusion. The i.v. infusions are an important part of this patient's therapy and may also be useful for other chronic transfusion patients for whom subcutaneous Desferal is inadequate for preventing continued iron accumulation. Some patients have successfully received their i.v. Desferal therapy at home, thereby decreasing hospitalization time and cost. Desferal induced moderate aluminum excretion in urine but had no effect on copper or zinc excretion.

Gas exchange during exercise in children with thalassemia major and Diamond-Blackfan anemia.

The two main goals of this study were: to determine how O2 uptake, ventilation, and CO2 production during exercise were acutely affected by transfusion in children with congenital anemia (thalassemia major and Diamond-Blackfan syndrome) requiring hypertransfusion and chelation therapy and to compare gas exchange responses to exercise of the anemic patients to normal values. Thirteen patients (age range 7-27) performed cycle ergometry with a progressively increasing work rate. Gas exchange was measured breath-by-breath. Tests were done before and after routine transfusion (mean increase in hematocrit 22%). The results were compared to 10 age-matched normal children who performed the same protocol on two occasions separated by a 2-day interval, and to the results of 109 normal children studied in this laboratory. Transfusion resulted in: a small, but significant increase in the anaerobic threshold (9%) and an increase in the slope of the relationship between O2-uptake and heart rates. Despite these improvements, the majority of the patients had abnormally low values of maximal O2 uptake, anaerobic threshold, and slope of the O2 uptake-heart rate relationship. The abnormalities were more marked in the older patients. Measurement of gas exchange during exercise may be helpful in determining an optimal hematocrit for patients on hypertransfusion regimens.

Hemolytic disease of the newborn. Review of deaths in California.

In order to find ways to decrease mortality from hemolytic disease of the newborn, a study was undertaken by physicians of the California Medical Association in cooperation with the California State Department of Public Health. Neonatal deaths during a two and a half year period were investigated and analyzed by review committees with the view of evaluating presumed deficiencies in management. The findings indicate that proper prenatal prediction and preparation by the physician for the management of HDN calls for earlier and more comprehensive use of warning signals, as well as a constant reappraisal of current technology. New advances in the management of HDN require increasingly close cooperation between patients, their physicians and consultants.

Renal lesions and clinical findings in thalassemia major and other chronic anemias with hemosiderosis.

Renal lesions found in 21 autopsied patients with hemosiderosis, 18 with beta-thalassemia, two with Blackfan-Diamond anemia, and one with aplastic anemia included: cellular glomeruli with increased mesangial matrix; hemosiderin deposit in visceral and parietal glomerular epithelial cells; greater hemosiderin deposit in terminal straight portions of proximal convoluted tubules and distal convoluted tubules than in connecting segments, or collecting tubules, connective tissue ferrugination; lipofuscin in tubular epithelium and vascular smooth muscle; infrequently, intimal or medial arterial thickening, and, in one patient with thalassemia, an infarct resulting from arterial thrombus. The progression of these lesions over the course of disease, and possible effects on the various lesions of high transfusion regimen, oral pancreatin, vitamin E supplementation, or treatment with intramuscular, subcutaneous, or intravenous desferrioxamine were evaluated. The results of urine and renal function studies of 4 of the autopsied patients (3 thalassemia, 1 Blackfan-Diamond anemia), and 14 patients with thalassemia and 4 with Blackfan-Diamond anemia who were not autopsied, are presented. Rarely significant until preterminal stages, the renal functional changes reflect distal more than proximal tubule dysfunction.