scholarly journals Dietary Intake Insufficient to Support Nutritional Adequacy in Patients with Thalassemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1361-1361
Author(s):  
Ellen B. Fung ◽  
Neogi Sushrita ◽  
Drucilla Haines ◽  
Connie Schroepfer ◽  
Ashutosh Lal
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Dietary Intake ◽  
Alpha Tocopherol ◽  
Nutritional Adequacy ◽  
Liver Iron ◽  
Vitamin C Deficiency ◽  
The Mean ◽  
The Relationship ◽  
Circulating Levels

Abstract Many patients with beta-thalassemia major have depressed circulating levels of essential micronutrients. These nutritional deficiencies may be caused by an elevated requirement for these nutrients, increased excretion and/or because of inadequate dietary intake. However, the relationship between dietary intake and circulating levels of key nutrients has not been explored. Therefore, the aim of this prospective, cross-sectional study was to quantitate intake using gold standard dietary assessment techniques, as well as to assess circulating levels of key micronutrients in the fasted state in a contemporary sample of subjects with transfusion-dependent thalassemia (age >5 years). Dietary intake was determined with the Block©2005 3-day semi-quantitative food frequency questionnaire (NutritionQuest, Berkeley, CA) completed within 3 months of a pre-transfusion blood sample. Dietary intake (mg/day) was calculated relative to the Institute of Medicine recommendations for age and gender. Intake was then compared to circulating levels of vitamin C, 25-OH vitamin D, alpha & gamma-tocopherol, zinc, copper and selenium. The usage of nutritional supplements was documented. All results were analyzed using STATA (v 9.3, College Station, TX). Forty-one patients (20 male, mean age 28.3 ± 10.7 years) with an average BMI of 22.1 ± 5.2 kg/cm2 and pre-transfusion hemoglobin of 10.9 ± 1.5 g/dL were enrolled. The mean liver iron concentration (LIC) measured by Ferritometer was 13.5 ± 11.3 mg/g dry liver-weight. As has been observed previously, 14 to 30% of patients had low circulating levels of Zn, Cu, 25-OHD, vitamin C and alpha-tocopherol. No deficiencies were observed for selenium. Patients consumed on average 1555 ± 835 kcal/d (80% of estimated energy requirement) and 1.3 ± 0.9 g/kg protein. Average dietary intake was inadequate (less than estimated average requirement) for Ca, Zn, Cu, and vitamins C, D, and E. Among patients with low circulating micronutrient levels, 86% of those with low serum zinc also had low dietary zinc intake; similarly, 88% of those with low circulating copper also had low copper intake. Significant inverse correlations were observed between LIC and blood concentrations of the antioxidants vitamin C (r = -0.62), alpha-tocopherol (r = -0.37) and zinc (r = -0.35). The relationship between iron overload and vitamin C was further explored in a retrospective sample of 49 patients where simultaneous values of both measures were available (228 samples). Vitamin C level progressively decreased with increasing iron burden. The mean vitamin C level was 0.57 ± 0.47 mg/dL with LIC >15 mg/g compared with 1.06 ± 0.45 mg/dL when LIC was <7 mg/g (P <0.001). Serum ferritin levels were not associated with vitamin C deficiency (plasma concentration <0.4 mg/dL) at mild to moderate degrees of liver iron overload. However, with extreme iron overload (LIC >25 mg/g), ferritin levels were significantly greater in the presence of vitamin C deficiency (6545 ± 2597 ng/mL versus 4720 ± 1915 ng/mL, p=0.045). These data suggest that iron overload negatively influences blood levels of several micronutrients. Moreover, dietary intake is insufficient to support circulating levels of nutrients in optimally transfused thalassemia patients. Nutritional adequacy is essential for optimal health, and vitamin C status can impact chelation efficiency. Future research should consider nutritional supplementation and health outcomes in patients with transfusion-dependent thalassemia. Disclosures No relevant conflicts of interest to declare.

Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1858-1858
Author(s):  
Konstantinos Sarantos ◽  
Patricia Evans ◽  
Maciej Garbowski ◽  
Bernard Davis ◽  
John B Porter
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Plasma Vitamin ◽  
Liver Iron ◽  
Vitamin C Deficiency ◽  
Vitamin C Supplementation ◽  
Iron Excretion

Abstract Background: Under conditions of iron overload, ascorbic acid is oxidised at an increased rate leading to a risk of vitamin C deficiency. With deferoxamine (DFO) standard therapy, vitamin C is usually given at a dose of 2–3mg/kg on the days of DFO infusion as this increases iron excretion by up to 30%. With deferarisox (DFX) chelation treatment, although supplementation is permitted, there is currently no information about the effects of vitamin C supplementation on iron excretion and it is often left to patients or their clinician’s discretion as to whether supplementation is given. With long-term treatment, in the absence of supplementation there is a potential risk that vitamin C deficiency will develop and this could influence response to treatment. Patients and Methods: We have measured fasting plasma vitamin C in 41 patients who have been on long term deferasirox treatment for transfusional iron overload for between 1.5 and 5 years. 32 of these patients had received no supplementation and 9 patients had received 2–3 mg/kg/ day of supplementation. We have examined whether trends in serum ferritin, myocardial T2* and liver iron, during the final year of observation, relate to plasma levels of vitamin C. Results: Fasting plasma Vitamin C was significantly lower in the 41 patients (mean=30.3μmol/l, SD=20.8) than healthy control patients (mean=60.29μmol/l SD=12.6) (P&lt;0.0001). Fasting vitamin C levels were significantly lower in patients without supplementation (mean=26.1μmol/l, n=32) (p=0.011) than in patients who received regular supplementation (mean=45.5μmol/l, n=9). In the 32 patients without supplementation 23 (72%) had plasma levels less than two standard deviations from the control mean. Fasting vitamin C levels after a minimum of 1 year treatment without vitamin C supplementation negatively correlated with liver iron concentration as estimated by T2* MRI. One patient, who was subsequently found to have the lowest fating vitamin c level (2.9μmol/l) developed clinical signs consistent with scurvy with severe gum disease requiring dental clearance. We found no difference in the change of ferritin trend, LIC decrease or cT2* trend in the patients receiving supplementation from those who did not. We found that the correlation between LIC and serum ferritin was less clear in deficient patients (&lt;36μmol/l or 2SD from the mean, r=0.51, p&lt;0.01) than replete patients (&gt;36μmol/l) (r=0.88, p&lt;0.0001). Conclusions: We conclude that with long-term deferasirox therapy without vitamin C supplementation, there is a significant risk of vitamin C deficiency with a potential for clinical scurvy. The risk of ascorbate deficiency is further increased at higher levels of body iron loading. These findings suggest that vitamin C supplementation (2–3mg/kg/day) should be recommended as standard for patients on long-term chelation therapy with deferasirox. It would also be of value to determine whether long term-response was improved by ascorbate supplementation.

The Relationship Between Antioxidant Nutrient Intake and Cataracts in Older People

2006 ◽  
Vol 76 (6) ◽  
pp. 359-366 ◽  
Author(s):  
Rodríguez-Rodríguez ◽  
Ortega ◽  
López-Sobaler ◽  
Aparicio ◽  
Bermejo ◽  
...  
Keyword(s):  
Vitamin C ◽  
Older People ◽  
Dietary Intake ◽  
Protective Effect ◽  
Elderly People ◽  
Nutrient Intake ◽  
Institutionalized Elderly ◽  
Weighing Method ◽  
The Relationship

This study investigated the relationship between the intake of antioxidant nutrients and the suffering of cataracts in 177 institutionalized elderly people (61 men and 116 women) aged ≥ 65 years. Dietary intake was monitored for 7 consecutive days using a "precise individual weighing" method. Subjects, who during their earlier years were exposed by their work to sunlight, had a greater risk of suffering cataracts (OR = 3.2; Cl: 1.1–9.3, P < 0.05) than those who worked indoors. A relationship was found between increased vitamin C intake and a reduced prevalence of cataracts (i.e., when comparing those above P95 for vitamin C intake with those below P5; (OR = 0.08; Cl: 0.01–0.75, P 0.05). Among subjects with cataracts, 12.1% had vitamin C intakes of < 61 mg/day (P10) and only 2.2% had intakes of > 183 mg/day (P95) (p < 0.01). Subjects who consumed > 3290 μg/day (P95) of lutein were less likely to have cataracts (OR = 0.086; Cl: 0.007–1.084; p < 0.05) than those whose consumption was < 256 μg/day (P5). In men, high intakes of zeaxanthin seemed to provide a protective effect against the problem (OR = 0.96; Cl: 0.91–0.99; p < 0.05). The results suggest an association exists between exposure to sunlight and the development of cataracts, and that vitamin C, lutein, and zeaxanthin offer some protection against this disorder.

scholarly journals Prevalence of Hypovitaminosis C and its Relationship with Frailty in Older Hospitalised Patients: A Cross-Sectional Study

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2117
Author(s):  
Yogesh Sharma ◽  
Alexandra Popescu ◽  
Chris Horwood ◽  
Paul Hakendorf ◽  
Campbell Thompson
Keyword(s):  
Vitamin C ◽  
Cross Sectional Study ◽  
Multivariate Logistic Regression Model ◽  
Cross Sectional ◽  
Vitamin C Deficiency ◽  
Frailty Assessment ◽  
Geriatric Unit ◽  
Hospitalised Patients ◽  
Micronutrient Malnutrition ◽  
The Relationship

Frailty is common in older hospitalised patients and may be associated with micronutrient malnutrition. Only limited studies have explored the relationship between frailty and vitamin C deficiency. This study investigated the prevalence of vitamin C deficiency and its association with frailty severity in patients ≥75 years admitted under a geriatric unit. Patients (n = 160) with a mean age of 84.4 ± 6.4 years were recruited and underwent frailty assessment by use of the Edmonton Frail Scale (EFS). Patients with an EFS score <10 were classified as non-frail/vulnerable/mildly frail and those with ≥10 as moderate–severely frail. Patients with vitamin C levels between 11–28 μmol/L were classified as vitamin C depleted while those with levels <11 μmol/L were classified as vitamin C deficient. A multivariate logistic regression model determined the relationship between vitamin C deficiency and frailty severity after adjustment for various co-variates. Fifty-seven (35.6%) patients were vitamin C depleted, while 42 (26.3%) had vitamin C deficiency. Vitamin C levels were significantly lower among patients who were moderate–severely frail when compared to those who were non-frail/vulnerable/mildly frail (p < 0.05). After adjusted analysis, vitamin C deficiency was 4.3-fold more likely to be associated with moderate–severe frailty (aOR 4.30, 95% CI 1.33-13.86, p = 0.015). Vitamin C deficiency is common and is associated with a greater severity of frailty in older hospitalised patients.

Scurvy mimicking as systemic lupus erythematosus

2021 ◽  
Vol 14 (6) ◽  
pp. e242958
Author(s):  
Narueporn Likhitweerawong ◽  
Nonglak Boonchooduang ◽  
Wipawee Morakote ◽  
Orawan Louthrenoo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin C ◽  
Dietary Intake ◽  
Lupus Erythematosus ◽  
Delayed Diagnosis ◽  
Paediatric Population ◽  
Autism Spectrum ◽  
Systemic Lupus ◽  
Vitamin C Deficiency ◽  
Spectrum Disorders

Scurvy is a disease caused by chronic vitamin C deficiency. The greater prevalence was found in the paediatric population with neurodevelopmental disorders such as autism spectrum disorders due to their restricted dietary intake. Our case reported a child with autism who presented with arthralgia and anaemia. Systemic lupus erythematosus was the first diagnostic impression, resulting in over investigation and delayed diagnosis of vitamin C deficiency. After the child was treated with ascorbic acid, the child’s symptoms resolved. This case highlighted the importance of developmental and nutritional history taking in the paediatric population. Furthermore, parents and physicians should be concerned about nutritional status, especially in children with restrictive dietary intake.

Myocardial and Hepatic Iron Overload and Cardiac Function In Sickle/Thalassemia Patients Of Italian Origin

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2252-2252
Author(s):  
Antonella Meloni ◽  
Giovan Battista Ruffo ◽  
Daniele De Marchi ◽  
Antonio Cardinale ◽  
Anna Pietrapertosa ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Liver Iron ◽  
Hepatic Iron Overload ◽  
The Mean ◽  
Magnetic Resonance Imaging Mri ◽  
Italian Origin

Abstract Introduction Sickle-thalassemia results from the combined heterozygosity for sickle-cell and β-thalassemia genes. This study evaluates myocardial and hepatic iron overload and cardiac function in Italian patients and explores their correlation with transfusions, age and sex. Methods Fifty-nine sickle-thalassemia patients (29 males, mean age 35.6±14.1 years), enrolled in the MIOT network underwent magnetic resonance imaging (MRI). T2* value for all 16 myocardial segments and global heart T2* value were calculated. Hepatic T2* value was converted into liver iron concentration (LIC). Cine images were acquired to quantify biventricular volumes and ejection fraction (EF). Results 55 (93%) patients had all segmental T2* values normal (>20 ms). Of the 4 patients with abnormal segmental T2* values, all showed an heterogeneous myocardial iron overload (some segments with T2*>20 ms and other with T2*<20 ms) and only one had a global T2*<20 ms. The mean global heart T2* value was 34.4±6.2 ms. The mean LIC was 5.9±6.5 mg/g/dw and 30 patients (50.8%) had a pathological value (≥ 3 mg/g dw). There was a statistically significant positive correlation between global heart T2* and age but with poor linearity (R=0.368; P=0.004) and there was not a significant correlation between age and LIC. Males and females had comparable global heart T2* values and LIC values. Twenty patients were regularly transfused, 32 received sporadic transfusions while 7 were not transfused. The comparison among the three groups is shown in Table 1. We did not find significant differences in the global heart T2* value while patients regularly transfused had significantly higher LIC than sporadically transfused patients. Biventricular volumes indexed by body surface area and ejection fractions were comparable among the groups. Conclusions In respect of MIO, the sickle/thalassemia patients are similar to patients with homozygous SCD for which iron overloading is relatively rare. Hepatic iron overload may develop also in no regularly-transfused patients, maybe due to increased absorption of iron from the digestive tract, characteristic of both SCD and thalassemia intermedia patients. This finding underlines the importance to monitor by MRI also no regularly transfused sickle/thalassemia patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 647-650 ◽  
Author(s):  
Anne Lenoir ◽  
Jean-Christophe Deschemin ◽  
Léon Kautz ◽  
Andrew J. Ramsay ◽  
Marie-Paule Roth ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Serine Protease ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Hepatic Iron ◽  
Master Regulator ◽  
Liver Iron ◽  
The Relationship

Abstract Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6−/− mice (characterized by increased hepcidin levels and anemia) and Bmp6−/− mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6−/− mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1421-1421 ◽  
Author(s):  
Robert I. Liem ◽  
Cynthia Rigsby ◽  
Richard J. Labotka ◽  
Andrew DeFreitas ◽  
Alexis A. Thompson
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if &lt; 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=&lt;0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range &gt; 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Longitudinal Follow-up From Newborn Screening Reveals Deletional Hemoglobin H Disease and Hemoglobin H Constant Spring Disease Are Distinct Thalassemia Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4260-4260
Author(s):  
Ashutosh Lal ◽  
Michael Lee Goldrich ◽  
Drucilla Foote ◽  
Mahin Azimi ◽  
Sylvia Titi Singer ◽  
...  
Keyword(s):  
Iron Overload ◽  
Newborn Screening ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Growth Failure ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
The Mean ◽  
Hemoglobin H Disease

Abstract Abstract 4260 Background: Alpha thalassemia disorders are rapidly increasing in North America. This has resulted in proposals for universal newborn screening (NBS) for hemoglobin H disease. However, the institution of routine newborn screening and construction of guidelines for early intervention requires longitudinal clinical data before setting national goals. Since 1995, California has performed universal screening for alpha thalassemia disorders. The longitudinal follow up of data from patients with hemoglobin H disorders diagnosed in the asymptomatic period provides essential information needed for formulating public health policy. Methods: Hemoglobin H disorders were diagnosed by high performance liquid chromatography with multiplex GAP-PCR assay to determine deletional hemoglobin H disease (deletion of 3 α globin genes, HbH) and the non-deletional hemoglobin H Constant Spring (α0 thalassemia with Constant Spring mutation, HCS). Longitudinal clinical data for all patients from the Northern California Thalassemia Center were analyzed. Ethnicity, growth data, clinic visits, hospitalizations, complications including splenectomy, transfusion, and iron overload were monitored. Quantitative liver iron concentration was determined by ferritometer. Results: 86 patients predominantly diagnosed through NBS were longitudinally followed. Out of these, 60 (70%) had HbH, 23 (27%) had HCS and 3 (3%) had other forms of hemoglobin H disease. The parental ethnicity in HbH was 79% Asian, 6% Hispanic, and 15% African-American (in one or both parents). All patients with HCS were of Asian ethnicity. Longitudinal data for hemoglobin revealed that anemia was more severe in HCS at all ages (p<0.001). Mean hemoglobin in HbH increased from 8.8 g/dL (6.9-10.6 g/dL) at 6 months to 9.4 g/dL (7.9-11.5 g/dL) at 5 years (p<0.001). However, mean hemoglobin in HCS remained unchanged from 7.4 g/dL (5.8-9.9 g/dL) at 6 months to 7.2 g/dL (3.8-8.7 g/dL) at 5 years (p=ns). There was no hemoglobin value <6.7 g/dL in 237 patient-years of observation of 60 patients with HbH. Compared to HbH, red blood cells in HCS had higher mean corpuscular hemoglobin (18.6 versus 16.6 pg, p<0.001) and mean corpuscular volume (65.2 versus 54.0 fL, p<0.001). The mean absolute reticulocyte count was 88.2 ×103/μL in HbH versus 235.1 ×103/μL in HCS (p<0.001), while the mean serum bilirubin was 0.56 mg/dL and 2.60 mg/dL, respectively (p<0.001). Clinical severity and complications were markedly worse in HCS in contrast with HbH. Growth was delayed in HCS with mean weight-for-age Z-score -0.91 compared with -0.06 in HbH (p<0.001). The mean height-for-age Z-score was also lower in HCS (-1.29) compared with HbH (-0.43, p<0.001). The striking susceptibility to acute worsening of anemia with infections requiring urgent blood transfusion was observed in HCS, but not in HbH. The probability of receiving one or more blood transfusion by 20 years was 3% in HbH and 82% in HCS (p<0.001). Transfusions in HCS were required for 13% infants and median transfusion-free survival was 6 years. Splenectomy improved hemoglobin by 2.9 g/dL (0.4 to 4.0 g/dL, p=0.012) and reduced transfusions in HCS. Iron overload, measured by serum ferritin and liver iron concentration, developed during the first decade in HCS and increased during follow up. Median ferritin in HCS between 12 –17 years was 330 ng/mL (66-1420 ng/mL). Serum ferritin in HbH did not increase between 0–18 years (median 40 ng/mL, range 5–182 ng/mL), but older patients showed strong positive correlation between age and ferritin (p<0.001). In patients with HbH or HCS undergoing ferritometer examination, the degree of serum ferritin elevation underestimated the liver iron concentration. Conclusions: Our data support the utility of a universal NBS program, particularly in areas where αCS mutation is prevalent, since young infants with HCS can develop life-threatening anemia. HCS is a serious disease that needs close follow-up by a specialty thalassemia center to plan for emergency and elective transfusions, measure iron overload, monitor growth failure and evaluate the need for splenectomy. In contrast, HbH is asymptomatic during infancy and childhood; its complications are age-dependent, and monitoring for hemosiderosis and growth failure is more important in older children. In summary, HCS should be recognized as a thalassemia syndrome distinct from HbH with a different screening and treatment approach. Disclosures: No relevant conflicts of interest to declare.

Therapeutic Phlebotomy in Children with Sickle Cell Anemia, Stroke, and Iron Overload: The SWiTCH Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1044-1044 ◽  
Author(s):  
Banu Aygun ◽  
Nicole A Mortier ◽  
Karen Kesler ◽  
Willliam H Schultz ◽  
Ofelia A. Alvarez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Recurrent Stroke ◽  
Venous Access ◽  
Study Entry ◽  
Liver Iron ◽  
History Of ◽  
The Mean

Abstract Abstract 1044 Background: Stroke With Transfusions Changing to Hydroxyurea (SWiTCH Clinical Trials.gov NCT00122980), an NHLBI-sponsored Phase III multicenter trial, compared chronic blood transfusions/chelation to hydroxyurea/phlebotomy for the reduction of recurrent stroke and improvement in iron overload management in children with sickle cell anemia (SCA) and history of overt stroke. To date, however, phlebotomy to manage iron overload has not been commonly performed in children, especially those with SCA. Objective: To describe the experience with SWiTCH phlebotomy procedures, including success rate, associated adverse events, and effect on liver iron stores. Methods: Quantitative liver iron concentration (LIC) was measured by liver biopsy at study entry. Only subjects with LIC > 5 mg Fe/gram dry weight liver (DWL) were eligible for randomization. Those randomized to hydroxyurea/phlebotomy received decreasing volumes of monthly transfusion during hydroxyurea dose escalation, which lasted 4–9 months. Phlebotomy was performed every 4±1 weeks after discontinuation of transfusions. The prescribed phlebotomy volume was 10 mL/kg (maximum 500 mL) for Hb ≥ 8.0 gm/dL, and 5 mL/kg for Hb 7.0–7.9 gm/dL. Phlebotomy was held if Hb was <7.0 gm/dL. Phlebotomy was performed over 30 minutes with immediate normal saline replacement, typically using peripheral venous access. Exit LIC by liver biopsy was obtained in those completing 30 months of therapy. Ferritin was monitored monthly in all subjects using a centralized laboratory. Results: Sixty-seven children (mean age 13.0 ± 4.0 years; range 5.2–19.0 years) with history of previous stroke and transfusion therapy for an average of 7.4 ± 3.8 years (range 1.5–15.5 years) were randomized to the hydroxyurea/phlebotomy arm. Most of them had also received chelation therapy: 47 (71%) with deferoxamine for an average of 4.8 ± 3.2 years, and 57 (86%) with deferasirox for 1.5 ± 0.8 years prior to study entry. Their average entry LIC was 16.5 ± 9.4 mg/gram DWL. Sixty of 67 children (90%) successfully transitioned to hydroxyurea after 7.2 ± 2.4 months of transfusion overlap; one subject had a stroke during overlap and six failed to demonstrate adequate response/compliance to hydroxyurea to safely discontinue transfusions. These 60 subjects received an average of 8 ± 3 transfusions providing 63 ± 44 mL/kg PRBCs before completing transition and commencing phlebotomy, and 3 ± 3 transfusions providing 19 ± 20 mL/kg PRBCs after starting phlebotomy, for various clinical indications. During the course of the study, a total of 935 phlebotomies were performed (mean 16 per subject) removing an average total volume of 127 ± 74 mL/kg per subject. The mean pre-phlebotomy Hb level on hydroxyurea (9.1 gm/dL) was not significantly different than the mean pre-transfusion Hb during the transfusion overlap period (9.0 gm/dL). Mean ferritin for these 60 subjects on the hydroxyurea/phlebotomy arm decreased from 3523 ± 2150 ng/mL at study entry to 2227 ± 1646 ng/mL (p<0.0001) at exit; and decreased in 50 of 60 subjects. For the 23 patients on the hydroxyurea/phlebotomy arm who completed 30 months of study treatment, the average LIC was unchanged (18.5 mg Fe/gram DWL at entry compared to 18.1 mg Fe/gram at exit, p=0.817). However, average ferritin level for these subjects was significantly lower at exit (4216 ± 2799 ng/mL vs 2356 ± 2032 ng/mL, respectively, p=0.0003). Of 968 protocol-directed phlebotomy procedures, 935 (97%) were performed; 94% of which were at full prescribed volume. Of the 33 phlebotomy procedures that were not performed, 11 were held due to Hb < 7.0 gm/dL and 9 due to poor venous access. There were only 33 grade 2 adverse events (3.5% prevalence) reported in 12 subjects and no serious adverse events. The most common complication was hypotension (9 events; 5 subjects) followed by dizziness, syncope, headache and weakness. Six subjects had a recurrent stroke but there was no temporal relationship to the phlebotomy procedures. Conclusions: Therapeutic phlebotomies were well-tolerated and did not result in worsening anemia or stroke recurrence in this cohort of children with SCA and previous stroke switched to hydroxyurea. Although ferritin levels decreased significantly, we did not demonstrate an overall decrease in LIC in this heavily iron overloaded cohort, most likely due to continued iron loading with transfusions in the overlap period and subsequent short duration of phlebotomy. Disclosures: Off Label Use: Use of hydroxyurea in children with sickle cell anemia.

Sign in / Sign up

Export Citation Format

Share Document