Non-invasive Quantitative MRI assessment of brain iron overload in patients with BThalassemia and Sickle cell disease

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ghada Samir Ibrahim ◽  
Fatma Soliman Elsayed Ebeid ◽  
Hend Galal Eldeen Mohammed Ahmed Samir Ibrahim
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Brain Mri ◽  
Control Group ◽  
Healthy Controls ◽  
Brain Iron ◽  
Cell Disease ◽  
Mri Study ◽  
Age And Sex

Abstract Background B-Thalassemia, sickle cell disease (SCD) and other inherited hemoglobin disorders are considered the most prevalent monogenic diseases worldwide. Secondary iron overload is one of the major complications in such groups of patients affecting many organs (e.g. liver, heart and endocrinal glands). Objective The current study will assess brain iron content ( using R2* values ) in the caudate and thalamic regions through quantitative brain MRI study in B-Thalassemia and SCD patients in comparison to age and sex-matched healthy controls. Also evaluation of the association with LIC (liver iron concentrations) and MIC (myocardial iron concentrations) was done. Methods A case control study on 30 patients (15 with B-thalassemia major and 15 with SCD) and 11 age and sex-matched healthy controls was carried out in the period between August 2018 till August 2019. Brain MRI study using multiecho fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. Also brain R2* values were correlated with the LIC and HIC in B-thalassemia and SCD groups. Results 15 transfusion dependent B-thalassemia (mean-age: 19.40 ± 4.31 years, 53.3% females), 15 SCD patients (SCD; mean-age: 16.93 ± 3.41 years, 40.6% females) and 11 age and sex matched healthy controls (HC; mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. No statistically significant differences were found between SCD and control group in all regions of interests No statistically significant differences were found between the three subgroups (p > 0.05) in right thalamus, left and right caudate regions. However, in B-thalassemia subgroup, patients had moderately significantly higher R2* values compared to the controls and SCD patients as regards the left thalamic region with mean R2* values (16.69 ± 1.34) Hz compared to (15.65 ± 1.10) Hz in the control group (p = 0.021) and (15.79 ± 0.77) Hz in the SCD group (p = 0.029). There were no significant correlations between LIC and HIC with brain R2* values of all regions of interests in both B-thalassemia and SCD subgroups. Conclusion MRI is a valuable, reliable, safe and noninvasive method for quantifying iron concentration (in cases of iron overload) in many organs as the liver and heart and it is now used internationally for regular follow up of LIC and HIC for monitoring of the chelation therapy in B-thalassemia and SCD patients. The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur. This may be explained by heavy chelation therapy regimens given to our patients due to their poor compliance so as to keep the pre-transfusion hemoglobin level above 10mg/dl to prevent detrimental cardiac affection as cardiac siderosis, arrhythmias including heart block, or even heart failure.

Evaluation of brain iron content in Egyptian Patients with Sickle cell disease and its impact on Neurocognitive functions

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohsen Saleh Elalfy ◽  
Fatma Soliman Elsayed Ebeid ◽  
Mohammed Ahmed Samir Ibrahim ◽  
Hanaa Midhat Abdel Gader Hussein
Keyword(s):  
Iron Overload ◽  
Brain Mri ◽  
Healthy Controls ◽  
Brain Iron ◽  
Cell Disease ◽  
Neurocognitive Functions ◽  
The Difference ◽  
Mri Study ◽  
The Brain ◽  
Age And Sex

Abstract Background Sickle cell disease (SCD) is considered the most prevalent monogenic diseases worldwide. Iron overload is one of the major complications in those patients, especially who in need for frequent transfusion, affecting many organs including the brain. MRI is a valuable, reliable and non-invasive method for quantifying iron concentration in many organs as the liver and heart and it is now used for monitoring of the chelation therapy in SCD patients. Several studies began reporting differences in global cognitive function, particularly for children with SCD, they are at a high risk for neurocognitive impairment they often scored lower on general IQ measures than healthy children which is due to iron overload in brain tissue from the chronic transfusions which can lead to strokes and may be a silent stroke. Objective The current study assessed brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI study in SCD patients in comparison to age and sex-matched healthy controls. Methods A case-control study recruited 32 patients with SCD and 11 healthy controls. Brain MRI study using multi-echo fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated for only 15 SCD patients and the 11 controls. All recruited SCD patients and controls were examined for the neurocognitive functions by these tests: Wechsler IV Intelligence Scale for Adult shows (Verbal, Perceptual, Memory, Processing and Total IQ), their all normal values between 90 – 110. Benton Visual Retention Test have cut of point at (> 4 or = 4). Those values are the same for the difference between the obtained correct and the expected correct, and the difference between the obtained error and expected error. Results The fifteen patient with SCD who underwent brain MRI were age and sex matched with the eleven healthy control (15 SCD patients: mean-age: 16.93 ± 3.41 years, 40.6% females and 11healthy controls: mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. As regards the brain MRI, there was no statistically significant differences between SCD and control group in all regions of interests (p > 0.05). Our study showed that 72.7% of our SCD patients had under threshold TIQ scores. Also18% of the patients showed moderate anxiety, 9% mild anxiety and 9% showed severe anxiety. Conclusion The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur.

scholarly journals Hidden Brain iron content in Sickle cell disease: Impact on Neurocognitive Functions

2021 ◽  
Author(s):  
Mohsen Saleh ElAlfy ◽  
Ahmed Samir Ibrahim ◽  
Ghada Samir Ibrahim ◽  
Hanaa Midhat Abdel Gader Hussein ◽  
Hend Galal Eldeen Mohammed ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Brain Mri ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Brain Iron ◽  
Cell Disease ◽  
Neurocognitive Dysfunction ◽  
Neurocognitive Functions

Abstract Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30±0.12 mg/kg/day. 68.9% of SCD had under- threshold IQ, 12.5% had moderate to severe anxiety and 60.8% had depression. There was no differences between SCD, BTM and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p=0.032). Mean right caudate R2* was higher in female than male (p=0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, negative correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients. Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload.

scholarly journals Brain Iron Content in Egyptian Patients with Sickle Cell Disease: Impact on Neurocognitive Functions

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Mohsen Saleh Elalfy ◽  
Ahmed Smair ◽  
Ghada Samir ◽  
Hanaa Hussein ◽  
Hend Mohammed ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Negative Correlation ◽  
Iron Content ◽  
Brain Mri ◽  
Brain Iron ◽  
Cell Disease ◽  
Neurocognitive Functions ◽  
Left Caudate

Background:Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment which may be due to iron overload in brain tissue or hemoglobin polymerization and endothelial dysfunction.Primary objectivewas measuring brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI in Egyptian adolescents and young adults with multi-transfused SCD in comparison to beta thalassemia major (BTM) and age- and sex-matched healthy controls.Secondary objectiveswere evaluating the impact of brain iron content on neurocognitive functions of SCD patients and its association with MRI assessment of liver iron concentration (LIC) and cardiac iron (myocardial T2*).Methods: 32 children and young adults with SCD (mean age: 15.3 ± 3.7, 19 males and 13 females), 15 BTM (mean age: 19.4 ± 4.3, 7 males and 8 females) and 11 healthy control age- and gender-matched were recruited. Thorough clinical assessment, hematological and serum ferritin were performed. Brain MRI study using multi-echo fast gradient echo sequence was performed only for 15 patients with SCD, 15 patients with BTM and 11 controls and brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. LIC and myocardial T2 were performed for; 15 with SCD and 15 with BTM. 32 SCD patients were examined for the neurocognitive functions; Wechsler IV Intelligence scale (verbal, perceptual, memory, processing and total IQ), Benton Visual Retention Test and Brief Psychiatric Rating Scale (BPRS).Results:For SCD patients their mean transfusion index was 174.70±63.98ml/kg/year and mean iron overload/day 0.30±0.12 mg/kg. 30 (93.8%) all SCD patients were on regular chelation therapy; 16 were on deferiprone and 16 were on combined chelation over last 5 years. Of those 32 SCD patients; 20 received concomitantly hydroxyurea therapy. Mean total IQ for SCD patients was 86.9±10.7; 68.9% had under- threshold <90 IQ and 27.5% had average (90-109) IQ. 12.5% of SCD patients had moderate to severe anxiety and 60.8% had of SCD patients had depression. No significant differences were found between SCD, BTM as regards LIC (p=0.102) No significant differences were found between SCD, BTM and control group in all regions of interests in brain MRI except that left thalamus R2* higher in BTM patients than both SCD and controls (p=0.032). R2* values of different regions of brain in relation with the studied parameters of SCD patients was not significant except that mean right caudate R2* was higher in female 17.4±0.8 than male 15.6±1.7 (p=0.044). The correlation coefficients showed no significant association between brain R2* and LIC or heart R2* values of SCD patients. There were positive correlation between left caudate R2* and both age and HbS%, negative correlation between transfusion index and right thalamus R2*, negative correlation between HbA% and left caudate R2* among SCD patients.Conclusion:Brain iron content in adolescents and young adults with SCD was not significantly different from either controls or BTM; SCD had high prevalence of neurocognitive dysfunction, which could not be explained by brain iron content or distribution. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Iron Depletion: An Ameliorating Factor for Sickle Cell Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
P. C. Giordano ◽  
W. Huisman ◽  
C. L. Harteveld
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Beneficial Effect ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Cell Disease ◽  
Laboratory Practice ◽  
Iron Depletion ◽  
Severity Of The Disease

We report some observations from our laboratory practice that might be important for the treatment of sickle cell disease (SCD). We describe data from two cases indicating that iron depletion might have a beneficial effect diminishing the formation of HbS in favor of HbF, possibly reducing the severity of the disease. We believe that it would be worthwhile to monitor the course of the disease comparing cases with identical genotypes with and without iron depletion, and we advise to consider chelation therapy to reduce iron overload in patients with SCD.

scholarly journals Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1136-1142 ◽  
Author(s):  
HC Kim ◽  
NP Dugan ◽  
JH Silber ◽  
MB Martin ◽  
E Schwartz ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Cell Disease ◽  
Donor Blood ◽  
Iron Load ◽  
Blood Usage ◽  
Hb S

Abstract Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Effectiveness, Time Utilization and Clinical Outcome of Partial Manual Red Cell Exchange in Patients with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2326-2326
Author(s):  
Kevin H.M. Kuo ◽  
David Barth ◽  
Richard Ward
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Venous Access ◽  
Iron Chelation Therapy ◽  
Red Cell ◽  
Cell Disease ◽  
Hemoglobin S

Abstract Abstract 2326 Introduction: Red cell exchange transfusion (RBCX) is used to treat and prevent selected complications from Sickle Cell Disease (SCD) where there is a need to reduce hemoglobin S level, blood viscosity, improve oxygen carrying capacity, and to avoid rapid iron overload from simple transfusions. Partial manual red cell exchange is sometimes employed in the chronic maintenance of low hemoglobin S levels. Data on the efficacy and clinical outcome of SCD patients on partial manual RBCX are limited. Methods: All partial manual RBCX from the University Health Network, a SCD comprehensive care center between April 1st, 2010 and April 30th, 2011 were retrospectively reviewed. Patients were exchanged at a frequency of 4 to 6 weeks where each session consists of two 500cc phlebotomy with an infusion of 500cc normal saline in between the phlebotomies, and transfusion of 2 units of packed red cells (pRBC). The procedure was repeated until pre-RBCX hemoglobin S (HbS) level <50% was reached (for patients without overt stroke for >4 years). Phlebotomy was reduced or omitted during episodes of symptomatic anemia at the discretion of the treating hematologist. Patients with poor venous access had indwelling line with chronic, therapeutic anticoagulation against line-related thrombosis. Results: Nineteen patients (16 HbSS, 2 HbSC, 1 HbSD) totalling 176 exchange sessions were reviewed. Indications for RBCX include primary and secondary stroke prevention (n = 14), recurrent painful vaso-occlusive crises intolerant or refractory to hydroxyurea (n = 3), pulmonary hypertension confirmed on right heart catheterization with hypoxia (n = 1), and prevention of intrahepatic cholestasis in a liver allograft (n = 1). Mean frequency of RBCX was 4.8 weeks (95% CI 3.9, 5.6 weeks). There were 2 transfusion-related (fever, pruritis) and 1 phlebotomy-related (pre-syncope) adverse events. There were 23 partial/cancelled phlebotomy sessions, mostly due to symptomatic anemia. Mean post-RBCX hematocrit was 0.296 (95% CI 0.280, 0.312) and pre-RBCX HbS level was 0.439 (95% CI 0.387, 0.490). Pre-RBCX HbS level of <50% was achieved in 74% of exchanges. Reasons for not achieving the target HbS level include: exchange interval >4.0 weeks, not on any transfusion regime prior to initiating partial manual RBCX, reduced or no phlebotomy in previous session, and non-adherence to treatment. Patients who were adherent to treatment had no recurrent events related to their initial indication for RBCX (one patient has possible Moyamoya formation but no clinically overt stroke), while 3 of the 6 patients who were not adherent had events during the study period (2 had painful vaso-occlusive crisis requiring hospital admission and 1 had new Moyamoya-like changes on cerebral angiogram). It took a median time of 90 minutes to phlebotomize 1,000cc whole blood and 176 minutes to transfuse two units of pRBC. There was no significant difference between the time required to phlebotomize or transfuse via peripheral vein versus an indwelling line (55 vs. 53 minutes/500cc; P = 0.7572 and 88 minutes vs. 88 minutes/unit; P = 0.9859). Eleven patients were also on iron chelation therapy for iron overload from previous simple transfusion, and patients who were adherent to RBCX (n = 7) had either a stable or reduction in ferritin level. Discussion: Patients who are adherent on partial manual RBCX can maintain a pre-RBCX HbS <50% with good clinical outcomes and low rates of adverse events, reduced blood consumption compared to automated RBCX, and obviate the need for ongoing iron chelation in those without pre-existing iron overload. In patients with iron overload, RBCX combined with iron chelation therapy can maintain iron balance. In patients with good peripheral venous access, indwelling lines do not confer an advantage to the speed of phlebotomy or transfusion. Patient with pre-RBCX HbS level >50% may benefit from a single session of automated RBCX to “reset” their HbS level before commencing chronic partial manual RBCX. Further prospective studies will aim to determine the rate of new or progressive silent infarcts and vasculopathy and reduction of iron balance via partial manual RBCX. Disclosures: Kuo: Novartis Canada: Research Funding.

Transfusional Iron Overload In An Adult Sickle Cell Disease Population: Epidemiology, Prevalence, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1005-1005 ◽  
Author(s):  
James Son ◽  
Hongyan Xu ◽  
Nadine J Barrett ◽  
Leigh G Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Organ Damage ◽  
Morbidity And Mortality ◽  
Genotype Distribution ◽  
Cell Disease ◽  
The Mean

Abstract Transfusional iron (Fe) overload remains a significant problem among patients with chronic, transfusion dependent anemias, especially in transfusion dependent ß-thalassemia (Thal) syndromes. If not treated vigorously with chelation, Fe overload in Thal is associated with significant organ damage, especially with chronic liver disease and cardiac abnormalities which can contribute to morbidity and mortality. In recent decades, the significance of Fe overload in sickle cell disease (SCD) has also been recognized especially among pediatric patients on chronic transfusion regimens predominantly for primary and secondary prevention of stroke. The prevalence and significance of this problem among adult SCD patients is less clear, although it is widely believed that episodic, mostly unnecessary transfusion practices play a more prominent role in this patient population. There have been reports of an association between iron overload and increased morbidity and mortality among adult SCD patients; it has also been speculated that the chronic inflammatory state that exists in SCD affords some degree of protection against severe organ damage through upregulation of hepcidin and sequestration of Fe in these patients. We performed a retrospective review of 635 adult SCD patients followed at our Center to define and ascertain the epidemiology, prevalence, etiology, and clinical correlates of transfusional Fe overload. Fe overload was defined as two consecutive serum ferritin values of > 1000 ng/ml. 80 patients (12.6%) met this criterion. Of these, 38 were male and 42 were female. Genotype distribution was: 73 SS, 3 S-β+ thal, 2 S-β0 thal and 2 SC. The mean age was 35.9 (range 18-69). Out of the 80 patients with transfusional Fe overload, 24 (30%) were/had been on a chronic transfusion regimen (23 for secondary or primary stroke prevention and one for childhood cardiomyopathy). Seventy percent of the patients (n=56) developed Fe overload from episodic transfusions predominantly performed at outlying community hospitals. The mean highest ferritin value was 4991 ng/ml (range 1,052-16,500). There was no correlation between ferritin levels and the number of hospitalizations or painful episodes (p=0.9). Thirty seven patients (46.2%) had a history of chelation therapy (with desferoxamine, deferasirox, or both). In 25 patients who have been on deferasirox for a period of 6 months or more, serum ferritin levels decreased from 4452.3 to 3876.6 ng/ml (p=0.3239). Our retrospective study shows that transfusional Fe overload is not rare among adults with SCD and develops predominantly as a result of episodic blood transfusions. This underscores the importance of the development and dissemination of evidence based guidelines, especially for episodic transfusions in SCD. A careful study of the extent and degree of organ damage associated with transfusional Fe overload in SCD and why less than half (46.2%) of patients are exposed to chelation therapy needs to be done. These studies should include liver iron concentration (LIC), cardiac iron and liver histology, when indicated, in parallel with serum hepcidin levels. The fact that the reduction in serum ferritin levels with deferasirox did not reach statistical significance in this cohort can be explained by the relatively small number of patients as well as by the short period (6 months) of exposure to chelation therapy. Disclosures: No relevant conflicts of interest to declare.

Treatment with Deferasirox Effectively Decreases Iron Burden in Patients with Sickle Cell Disease and Thalassemia Intermedia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1517-1517
Author(s):  
Ersi Voskaridou ◽  
Eleni Plata ◽  
Panagiota Stefanitsi ◽  
Marousa Douskou ◽  
Dimitrios Christoulas ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Renal Impairment ◽  
Serum Creatinine ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Intermedia ◽  
Cell Disease ◽  
Liver Iron

Abstract Abstract 1517 Poster Board I-540 Iron overload was not thought to be an important issue in sickle cell disease (SCD) in the past because of the short life-span of SCD patients. However, the increase in longevity during the recent years has been associated with clinical evidence of iron overload in some SCD patients due to accumulation of transfusional iron, increased absorption associated with intensive erythropoiesis and iron deposition as a result of continuous hemolysis. Therefore, iron overload may play an important role in the severity of SCD and iron chelation has a definite indication in several SCD cases. Thalassemia intermedia (TI) encompasses a wide clinical spectrum of beta-thalassemia phenotypes. Iron overload is alsofrequently present in TI patients as a result of increased intestinal iron absorption secondary to chronic anemia and to sporadic blood transfusion therapy, which may be administered intermittently when hemoglobin (Hb) levels fall <7 g/dL. Thus, a variable rate of iron loading, reaching toxic levels in some patients, was seen in a series of intermittently transfused TI patients who need adequate chelation therapy. Deferasirox (Exjade®) is a once-daily orally administered iron chelator approved for the treatment of transfusional iron overload in patients with transfusion-dependent anemia. Here, we report on the efficacy and safety of deferasirox in iron-overloaded patients with SCD and TI. We evaluated 18 adult patients with SCD (8M/10F; mean age 41.3 ± 8.5 years) and 11 with TI (5M/6F; mean age 41.2 ± 6.5 years) who had serum ferritin levels >1000 ng/mL and who were sporadically transfused with <20 units of red blood cells before starting deferasirox treatment for up to 12 months. Twenty-four patients (15 with SCD and 9 with TI) and 5 (3 with SCD and 2 with TI) patients were initially treated with deferasirox at 10 and 20 mg/kg/day, respectively, based on the number of blood transfusions received before the initiation of treatment. After 3 months, dose adjustments (increases) were allowed in increments of 5 mg/kg/day every 3 months as required to reduce markers of iron overload. Total iron burden was monitored by measuring serum ferritin levels before and monthly after starting deferasirox, while liver iron concentration and cardiac iron burden were measured by magnetic resonance imaging (MRI) T2 and T2* parameters at baseline and 12 months after deferasirox treatment. Left ventricular ejection fraction (LVEF) by MRI, and 24-hour proteinurea (Prot 24h) before and after treatment, were also measured. Hb levels, serum creatinine, cystatin-C (a sensitive marker of renal impairment), alanine (ALT) and aspartate aminotransferase (AST) were measured before and every month during deferasirox treatment. Serum ferritin level was significantly reduced after 12 months of deferasirox treatment in both SCD (mean±SD: from 1993±997 ng/ml to 1106±1016 ng/ml, p<0.001) and TI patients (from 2030±1040 ng/ml to 1165±684 ng/ml, p=0.02). Similarly baseline liver T2 and T2* significantly increased following 12 months of therapy in SCD (from 21.1±5.7 ms to 27.4±8.0 ms, p=0.001 and from 4.1±3.8 ms to 6.0±3.4 ms, p=0.013, for T2 and T2* respectively) and TI patients (from 20.1±4.1 ms to 23.7±6.2 ms, p=0.01 and from 3.4±3.0 ms to 4.4±3.0 ms, p=0.02, for T2 and T2* respectively). Mean cardiac T2* and LVEF were normal at baseline and did not significantly change after 12 months of treatment in SCD and TI patients. There were also no significant changes in mean serum creatinine, Hb or Prot 24h levels after 12 months of deferasirox treatment, while mean ALT and AST levels significantly decreased over 12 months in both groups of patients (p<0.02 and p<0.04 for SCD and TI, respectively). In terms of cystatin-C, there was a significant increase after 12 months of treatment in SCD patients (from 0.97±0.32 mg/l to 1.12±0.4 mg/l, p<0.001) but not in TI patients, in whom the increase was of borderline significance (from 0.98±0.23 mg/l to 1.13±0.27 mg/l, p=0.094). These data indicate that, over 12 months, deferasirox significantly reduced liver iron burden and serum ferritin levels in these iron-overloaded patients with SCD and TI. The decreases in ALT and AST are suggestive of an improvement in liver function, while there must be some caution for renal impairment, mainly in SCD. This study indicates that deferasirox provides effective iron chelation therapy in these patients without any significant adverse effects. Disclosures No relevant conflicts of interest to declare.

scholarly journals Assessment of Iron Overload and Chelation Therapy in Adult Inpatients with Sickle Cell Disease

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Bohm Nicole ◽  
Toussaint Brittany ◽  
Sarratt Stefanie ◽  
Vaughan Leigh ◽  
Duckett Ashley
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Cell Disease

scholarly journals The Safety of Chelators for Iron Overload in Sickle Cell Disease: A Brief Systematic Review

Acta Medica ◽  
2019 ◽  
Vol 50 (3) ◽  
pp. 50-60
Author(s):  
Basseem Radwan ◽  
İ. İpek Boşgelmez
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Cell Disease ◽  
Chromosome 11 ◽  
High Concentration ◽  
African Countries

Sickle cell disease (SCD) is a group of disorders that affects hemoglobin due to a mutation of the hemoglobin beta gene (HBB) on chromosome 11. Patients with SCD have atypical hemoglobin molecules called hemoglobinS (HbS), which distort erythrocytes into a “sickle-shape”. Typical symptoms of SCD include periodic episodes of pain, repeated infections, and anemia. This disorder is abundant in sub-Saharan African countries, the Mediterranean region, and also appears in some southern provinces in Turkey. Because of the high concentration of HbS in patients, a high risk of chronic anemia and vaso-occlusive events, such as stroke may deteriorate suddenly. In these conditions, transfusion of blood, especially erythrocytes, can be life-saving. However, chronic blood transfusions may lead to iron overload in SCD patients. Erythrocyte transfusion is associated with a higher risk in most patients with SCD than in the general population. Therefore, chelation therapy has become an important component of the transfusion program to prevent complications of iron accumulation in organs such as liver and heart. In this study, we sought to conduct a systematic review to assess the safety of iron chelating agents used by SCD patients with iron overload mainly due to necessary blood transfusion regime. Our evaluation revealed that in general iron chelation therapy, either deferasirox, deferoxamine or deferiprone, remains the most effective and safest available method to treat iron overload in SCD. Furthermore, current reports do not reflect any significant safety concerns against the use of available chelators.

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