Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi‐center study of iron overload

Fung, Ellen B.; Harmatz, Paul; Milet, Meredith; Ballas, Samir K.; Castro, Laura De; Hagar, Ward; Owen, William C.; Olivieri, Nancy F.; Smith‐Whitley, Kim; Darbari, Deepika S.; Wang, Winfred C.; Vichinsky, Elliott

doi:10.1002/ajh.20809

Cited by 139 publications

(125 citation statements)

References 31 publications

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“…After enrollment, each subject's medical history was reviewed by subject interview and medical record review as previously described [21]. The subject interview questionnaire included sections on demographics, medical, orthopedic and surgical history, recent hospitalizations, family history of endocrine complications, nutritional supplements, medications, tobacco and alcohol usage.…”

Section: Methodsmentioning

confidence: 99%

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Fung¹,

Harmatz²,

Milet³

et al. 2008

Bone

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Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6±0.7 yrs), 203 subjects with TxSCD (44% Male, 24.7 ±0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 yrs) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p=0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

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Section: Methodsmentioning

confidence: 99%

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Fung¹,

Harmatz²,

Milet³

et al. 2008

Bone

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“…This hereditary disorder of metabolism can lead to organ damage and mortality [31,32], if left undiagnosed and untreated. Iron deposition in the parenchymal tissues of thalassemia patients can be observed within a year of the onset of regular blood transfusions [33].…”

Section: Dental Infectionsmentioning

confidence: 99%

Orodental Considerations in Thalassemia Patients

S¹,

AlKathemi²

2016

Journal of Hematology and Blood Disorders

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“…Since patients with SCD now have improved life expectancy, transfusion therapy may be administered over considerably longer periods of time, increasing the potential for both allo-immunization and iron accumulation. Body iron overload has been shown to be associated with morbidity and mortality in patients with SCD [36,37] and a positive correlation has been observed between the severity of iron overload and frequency of hospitalization [38]. There is also growing evidence to suggest a role for iron overload in the development of other SCD comorbidities such as pulmonary hypertension and cirrhosis [39,40].…”

Section: Commentarymentioning

confidence: 99%

Iron chelation therapy for patients with sickle cell disease and iron overload

Inati¹,

Khoriaty²,

Musallam³

et al. 2010

American J Hematol

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A 21-year-old male with sickle cell disease (SCD) presented with severe pallor. He had received a total of 100 red blood cell (RBC) units in his lifetime, had a mean serum ferritin level of 3133 ng/ml, and liver iron concentration (LIC) of 12 mg Fe/g dry weight (dw). He was started on subcutaneous deferoxamine (DFO) infusions at a dose of 56 mg/kg/d, five days a week (equivalent to 40 mg/kg/d, seven days a week) and continued to receive 8-10 RBC units/year as treatment for pain. During the first six months of chelation therapy, his serum ferritin levels fell by around 50% of the pretreatment value, but then started to increase back up to the baseline values. The patient was noncompliant with DFO therapy. He experienced pain at the site of injection, could not sleep and was concerned about carrying a pump and not being accepted by his peers. He dropped out of college and abstained from all social activities. He was referred to a psychologist; however, this failed to improve compliance and he opted to stop DFO therapy altogether.The role of iron chelation therapy has long been acknowledged in the management of iron overload in patients receiving blood transfusion therapy; however, data specific to the treatment of patients with SCD are limited. DFO (Desferal 1 ; Novartis Pharma AG, Basel, Switzerland) was the first iron chelator to be licensed, more than 40 years ago, for chronic iron overload as a result of transfusion-dependent anemia and remains the current reference standard iron chelator. The efficacy and safety of DFO is well established in patients with b-thalassemia major [1-3]; however, clinical evaluation in SCD-specific populations is limited. Early small-scale studies of transfused patients with SCD showed that DFO was able to increase urinary iron excretion [4,5] and intensive chelation regimens in heavily iron-overloaded patients with SCD showed acceptable efficacy and safety [6][7][8]. In these small-scale studies, there were no reported incidences of impaired hearing or visual acuity, toxicities that have been noted in patients with b-thalassemia major and other rare anemias when doses are inappropriately high for the level of iron overload [9]. However, careful regulation of dosage and regular audio-visual monitoring is still advised. Increased zinc excretion demonstrated at very high DFO doses (180 mg/kg) [8] may lead to extreme zinc deficiency in patients with SCD who may already have decreased plasma zinc levels [10]. The verification of possible adverse events specific to patients with SCD most certainly requires further study.The major limitation of DFO is the requirement for frequent, slow parenteral administration, which can be painful and inconvenient. Compliance has a noticeable impact on a patient's response to therapy and can have serious consequences, as described in this case. In patients with b-thalassemia major, the demands of DFO therapy have been shown to have a negative impact on quality of life and mental health [11]. The impact of infusions may be greatest for adolescents and y...

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Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi‐center study of iron overload

Cited by 139 publications

References 31 publications

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Orodental Considerations in Thalassemia Patients

Iron chelation therapy for patients with sickle cell disease and iron overload

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