Abstract

Vitamin and mineral deficiencies have been well described in non-transfused patients with sickle cell disease (SCD). Levels of biomarkers of oxidant damage are increased in both SCD and thalassemia major (TM), and levels of antioxidants have been shown to be lower in both diseases. Hypermetabolism, increased hemolysis and denaturation of unpaired globin chains contribute to oxidative stress in SCD and TM. Chronic transfusions, initially thought to be protective against oxidation by marrow suppression, may have the opposite effect due to the well-known propensity of iron to promote free radical generation. Methods: To test this hypothesis, we measured levels of vitamins A, B1, B6, C, D, E as well as selenium, zinc, copper and carnitine and compared them to liver iron concentrations in chronically transfused SCD and TM patients. All patients were required to fast overnight and to hold their iron chelator for 24 hours prior to blood draws. Samples were processed by routine clinical processing (Quest Nichols Institute, San Juan Capistrano, CA). Results were expressed as the percentage of patients outside the reference range for the referral laboratory. Twenty four patients with TM and 43 patients with SCD were studied.

Abnormal Values In Transfused Patients

SC (%abn)TM (%abn)
73.7 52.4 
B1 38.5 37.5 
B6 34.2 34.8 
Folate 28.6 37.5 
56.7 66.7 
D25 74.4 50.0 
D1, 25 48.6 39.1 
Se 67.5 75.0 
Zn 24.3 8.3 
Carnitine (Free) 22.2 41.7 
SC (%abn)TM (%abn)
73.7 52.4 
B1 38.5 37.5 
B6 34.2 34.8 
Folate 28.6 37.5 
56.7 66.7 
D25 74.4 50.0 
D1, 25 48.6 39.1 
Se 67.5 75.0 
Zn 24.3 8.3 
Carnitine (Free) 22.2 41.7 

Results: The results in the table demonstrate that over half the patients were deficient in A, C, D and selenium. A third of the patients had low levels of B vitamins and folate (despite replacement doses in the latter), as well as carnitine. B12 levels(not shown) were normal. E levels (not shown) were low in only a few patients. Deficiency profiles were remarkably similar between the two diseases: only copper was significantly higher in the SCD patients (34.2% elevated vs 0% in TM). B6 and folate were weakly correlated with hepatic iron concentration (r2 = −0.12, −0.18). B6, folate, D25-OH, and D1,25 OH levels declined with age. These results demonstrate that chronically transfused patients have significant deficiencies in nutrients which are involved in buffering oxidant stress, regardless of their diagnosis. Severity of iron overload was not a strong predictor of these abnormalities; although the precise explanation is not known, chronic anemia may be the unifying factor. The magnitude of B1, B6, C and D deficiencies in some patients was well into the range known to cause serious complications. These combined abnormalities may contribute to the morbidity of chronically transfused patients with SCD and TM.

Author notes

Disclosure:Consultancy: Drs Wood and Coates have served as consultants to Novartis. Research Funding: Drs Wood and Coates ahve received research funding from Novartis and Apotex. Honoraria Information: Drs Wood and Coates have received honoraria from Novartis and Apotex. Membership Information: Drs Claster, Hofstra and Coates are members of the Exjade speakers bureau. Dr Wood is an advisor to the Exjade Speaker’s Bureau.