Iron chelation therapy in sickle cell anemia

Iron stores, ascorbic acid levels, and urinary excretion of iron in response to deferoxamine (DFO) were studied in nine patients with sickle cell anemia who had received 8–55 liters of red blood cells. Ferritin levels ranged from 2, 168 to 6,300 ng/ml and were elevated even in patients who had normal serum iron concentrations. Leukocyte ascorbic acid levels were low in three patients. Urinary iron excretion in response to 2.0 gm DFO administered as a 12-hour subcutaneous infusion after ascorbic acid supplementation was 13–39 mg/24 hours. With this method of DFO therapy daily, urinary iron excretion would exceed transfusional iron accumulation in eight of nine patients. Following the intramuscular injection of 0.75 gm DFO, urinary iron excretion was 5–16 mg/24 hours. Iron excretion would exceed iron accumulation in only one of nine patients with this method of DFO therapy. Urinary iron excretion in response to 1.5 gm DFO infused intravenously in 18 hours after ascorbic acid supplementation was 11–38 mg/24 hours. In six regularly transfused but nonchelated patients iron excretion in response to intravenous DFO had increased 46–107%, in comparison with previous studies 15–22 months before. These data indicate that negative iron balance can be obtained in regularly transfused patients with sickle cell anemia by the use of overnight subcutaneous infusions of DFO. Urinary iron excretion in response to DFO should be evaluated periodically in appropriate patients with sickle cell anemia to determine the proper time for the institution of chelation therapy.     

Iron chelation therapy in sickle cell disease

Iron chelation therapy with deferoxamine enhances iron excretion and removes excessive tissue iron in regularly transfused patients with sickle cell disease. Long-term studies of deferoxamine in other hemoglobinopathies demonstrate that regular chelation therapy also reduces iron-related organ damage and mortality. Careful design of chelation regimens and attention to compliance are critical elements of successful therapy. The role of new chelators in sickle cell disease is currently under investigation.     

Isobutyramide therapy in patients with sickle cell anemia

We have administered Isobutyramide as a suspension over a period of 3 months, from a starting dose of 50 mg/kg/day up to 150 mg/kg/day, to four adult sickle cell (SS) anemia patients. The maximum dose was maintained for 3 weeks. The blood counts remained stable and the Hb F levels decreased slightly. The ^Gγ levels increased at the end of the trial, suggesting activation of the ^Gγ gene at the highest dose of Isobutyramide. Three patients showed a stable rate of hemolysis, while in one patient, an increase of lactate dehydrogenase occurred. None of the patients experienced pain crisis or organ-specific crisis, but all four complained about mild epigastric burning and a bitter taste. After the first month of treatment one patient complained about intolerable epigastric discomfort which was relieved by Omeprazole. Another patient complained about increasing dyspepsia in the 12th week leading to the termination of the trial. Oral Isobutyramide administration does not qualify as an effective treatment of SS patients. © 1995 Wiley-Liss, Inc.     

Iron overload and iron chelation therapy in thalassaemia and sickle cell haemoglobinopathies

This paper reviews the factors governing the rate of iron loading and iron toxicity in the thalassaemia syndromes and sickle cell disease. It outlines the main determinants of iron mobilization by the iron-chelating drug, desferrioxamine, together with the effects of this drug in clinical practice.     

Improved exercise performance after exchange transfusion in subjects with sickle cell anemia

Ten patients with sickle cell anemia underwent partial exchange transfusion with hemoglobin-A-containing cells using a technique that allowed hemoglobin concentration and blood volume to remain constant. The mean fraction of hemoglobin-A in these patients increased from 9% to 55%, but the mean hemoglobin concentration increased by only 1.44 g/dl. The exchange resulted in a large improvement in submaximal exercise capacity: the mean of the anaerobic threshold (the work at which lactic acid begins to accumulate in the blood) increased from 68 to 114 W. The mean work performed at a heart rate of 170/min, an estimation of maximal work capacity, increased from 128 to 187 W. Improved exercise performance after partial exchange transfusion may result from the superior flow properties of hemoglobin-A-containing red cells. Furthermore, we believe that exercise testing in sickle cell anemia has great potential utility as a means to monitor therapy and to evaluate the benefits of exchange transfusion.     

Aged garlic extract therapy for sickle cell anemia patients

Background  

Sickle cell anemia is one of the most prevalent hereditary disorders with prominent morbidity and mortality. With this disorder oxidative, phenomena play a significant role in its pathophysiology. One of the garlic (Allium sativum L.) formulations, aged garlic extract (AGE), has been reported to exert an anti-oxidant effect in vitro, we have evaluated the anti-oxidant effect of AGE on sickle red blood cells (RBC).     

Health‐related quality of life in children with sickle cell anemia: Impact of blood transfusion therapy

The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre‐existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health‐related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group. A total of 89% (175 of 196) of the randomly allocated participants had evaluable entry and exit HRQL evaluations. The increase in Change in Health, measured as the child's health being better, was significantly greater for the transfusion group than the observation group (difference estimate = ?0.54, P ≤ 0.001). This study provides the first evidence that children with SCA who received regular blood transfusion therapy felt better and had better overall HRQL than those who did not receive transfusion therapy. Am. J. Hematol. 90:139–143, 2015. © 2014 Wiley Periodicals, Inc.     

Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia

Hydroxyurea reduces the frequency of acute pain in sickle cell disease (SCD). We sought to determine if hydroxyurea therapy affects cell free DNA (cfDNA) levels in SCD. cfDNA levels fell in all 10 patients studied; before hydroxyurea, mean was 1,879 (95% CI 1,104-3,199) GE/mL; after hydroxyurea, mean was 780 (95% CI, 634-959) GE/mL (P = 0.002). Mean cfDNA level in the 10 HbSS adults prior to starting hydroxyurea was also significantly higher than that in 115 HbSS case controls who had never taken hydroxyurea (1,879 vs 975 GE/mL, P = 0.02). cfDNA levels may be useful in monitoring response to hydroxyurea therapy in SCD.     

Transfusional hemosiderosis and combined chelation therapy in sickle thalassemia

Although the indications for transfusions in sickle cell syndromes are well listed, and chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload, multi-transfused, non-compliant to long-term chelation therapy patients confront the complication of iron overload and secondary hemosiderosis. In thalassemia major patients, combined therapy with desferrioxamine and deferiprone has maximized tissue iron removal and may reduce the overall occurrence of hemosiderotic heart failure. Despite this, safety and contradictions of chelating agents are still controversial. The aim of this report is to present the results of this combination in a long-term transfused sickle beta-thalassemic patient suffering from severe heart failure and liver dysfunction.     

A prophylactic transfusion program for children with sickle cell anemia complicated by CNS infarction

CNS infarction is a devastating complication in sickle cell anemia. Episodes are frequently repetitive and often result in permanent neurologic abnormalities. In an attempt to prevent such recurences a periodic transfusion program was begun at the Children's Hospital of Michigan in 1969. Twenty-one children currently on the program receive buffy-coat poor transfusions on an out-patient basis every 3 weeks. Of 15 who have been on the program for periods of from 9 months to 5 ¾ years, none have had progression of neurologic abnormalities, and several have had definite improvement in neurologic function. One child who was not brought in regularly had recurrent CNS infarction. The only recognized complication has been one instance of serum hepatitis. While such a transfusion of neurologic abnormalities resulting from recurrent CNS infarction in sickle cell anemia.