Hemoglobin H-Constant Spring in North America: A Common Alpha Thalassemia with Frequent Complications.

Abstract The α-globin Constant Spring (CS) mutation (α142 STOP → Gln; TAA → CAA) is the most prevalent non-deletional thalassemia in south East Asia and southern China. DNA diagnosis of Hb H Constant Spring (Hb H CS; 2 α-gene deletions and 1 CS mutation) is often required because it can be missed by electrophoresis. The clinical phenotype of Hb H CS is more severe than classical Hb H disease. We sought to characterize the unique hematological and clinical features of Hb H CS patients, especially compared to those with Hb H disease, who were identified through the Thalassemia Clinical Research Network (TCRN). A total of 836 patients enrolled in the TCRN registry in Canada and the U.S. (2001 to 2005) were screened for this analysis. Genotyping of 836 thalassemia patients identified 106/836 (12.7%) with Hb H and 46/836 (5.5%) with Hb H CS. 2 had other non-deletional mutations. Among Hb H CS patients, 48% were female; mean age was 13±11 years. Among patients who had spleens, splenomegaly was more prevalent in Hb H CS than Hb H patients (16% vs 1%, p=0.001). Among Hb H CS patients who had splenomegaly, average spleen span was 3.67 ± 2.25cm. 13% of the Hb H CS and 2% of the Hb H patients had their spleen removed (p=0.005). Mean Hb level was higher in the splenectomized Hb H CS patients than in the non-splenectomized Hb H CS patients (9.85 ± 2.25 g/dL vs. 8.25 ± 0.76 g/dL, p=0.006). Post-splenectomy portal vein thrombosis was reported in 1 Hb H CS patient. 7.5% (3/40) of non-splenectomized Hb H CS patients had bacteremia or infections requiring intravenous antibiotics. 8.7% (4/46) of Hb H CS patients underwent cholecystectomy. 24% of HbH CS and none of the Hb H patients were placed on regular transfusions (>8/year) and chelation therapy. Mean age of initiation of transfusions was 3.5±1.3 years (range 2–5 years). Mean ferritin level was higher in the non-transfused Hb H CS patients than in the Hb H patients (369.9 ± 409.9 ng/ml vs 175.9 ± 304.2 ng/ml, p=0.01), suggesting increased gastrointestinal iron absorption in Hb H CS. In 5 transfused Hb H CS patients, liver iron concentration was obtained showing elevated levels (27.2 ± 13.9 μgm/gm dry wt). Growth delay was more apparent in the Hb H CS patients (n=19) compared to 20 Hb H patients (Mean height Z score: −1.34 ± 0.98 for Hb H CS vs −0.82 ± 1.15 for Hb H (p=0.16) and mean weight Z score: −1.15 ± 0.88 for Hb H CS vs. −0.83 ± 1.61 for Hb H (p=0.47)). Bone density scans in Hb H CS patients revealed a higher prevalence of low bone mass than that detected in Hb H patients: mean L1-L4 spine Z/T-score of −1.60 ± 0.86 vs. −0.93 ± 0.80 (p=0.02). 40% (4/10) of adult female Hb H CS patients had 1 or more successful pregnancies, some requiring transfusion support through pregnancy. Patients with Hb H CS have a severe phenotype of α-thalassemia. They have moderately severe anemia, which sometimes requires regular transfusions, splenectomy, or both. Patients with Hb H CS commonly have iron overload, growth delay, and reduced bone mass. Early diagnosis in the neonatal period, regular monitoring, and appropriate treatment considerations for initiation of regular transfusions are key.

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In-Accuracy Of Bone Density Measurements By DXA In Patients With Hemoglobinopathies and Iron Overload

Blood ◽

10.1182/blood.v122.21.966.966 ◽

2013 ◽

Vol 122 (21) ◽

pp. 966-966

Author(s):

Haven M. Allard ◽

Marcela G. Weyhmiller ◽

Ashutosh Lal ◽

Ellen B. Fung

Keyword(s):

Lumbar Spine ◽

Iron Content ◽

Iron Concentration ◽

Lumbar Vertebrae ◽

Healthy Controls ◽

Z Score ◽

Liver Iron Concentration ◽

Liver Iron ◽

Liver Iron Content ◽

Z Scores

Abstract Introduction When monitoring bone health in patients with hemoglobinapathies, it is unknown if iron in surrounding tissues can lead to inaccuracies in the 2-dimensional assessment by Dual Energy X-ray Absorptiometry (DXA). Objective The aims of this study were: 1) to determine if the accuracy of lumbar spine assessment by DXA is affected by high liver iron concentration in patients with Sickle Cell Disease (SCD) or Thalassemia (Thal), 2) to test the effect of high tissue iron on vertebral Z-scores using phantoms, 3) to explore the ability to account for potential high-iron content effects when performing DXA examinations. Methods This study consisted of a retrospective chart review of data collected by the Children’s Hospital & Research Center Oakland, Bone Density Clinic and Iron Measurement Program. Data from both DXA and Super Conducting Quantum Interference Device (SQUID) examinations collected between 2002 and 2013 from were abstracted. Only those patients with a diagnosis of SCD or Thal, who had a DXA and SQUID measurement within the same year were divided into an iron overload group (liver iron concentration (LIC) >3,000 µg Fe/g wet) and low iron (LIC <500 µg Fe/g wet) group. These patients were compared with healthy controls of which only 13 had both DXA and SQUID tests, 34 had DXA only. The 34 healthy controls without a SQUID test were included because it was assumed, based on their health screen that their liver-iron content would not interfere with DXA. In order to explore aim 1, a lumbar spine scan, by DXA, of each subject was re-analyzed to compare the derived areal bone mineral density (aBMD) Z-scores of lumbar vertebrae that are covered by the liver (presumed L1 or L1/L2) with the Z-scores of the lumbar vertebrae not covered by the liver (L3/L4). To explore aim 2, phantoms were designed to mimic the geometry of iron loaded tissues in order to explore the contribution of iron in specific tissues on the accuracy of DXA assessments. Phantoms were constructed using KNOX® brand gelatin and iron(II) sulfate heptahydrate and had concentrations ranging from 3,000 to 7,000 ug Fe/g gelatin. The iron-loaded phantoms were positioned obtusely overlying L1/L2 of the DXA daily quality control phantom to mimic the position of the liver. All data were analyzed by STATA ver.9.2 and were considered significant with a p<0.05. Results Data from 102 total visits abstracted from 88 subjects [19 SCD (13 F), 24 Thal (12 F), age: 30.1 ± 11.9 years, mean ± SD], and 45 healthy controls (24 F, age: 25.4 ± 11.0 yrs) were analyzed. The SCD and Thal group had an average LIC by SQUID of 4651 ± 2079 µg Fe/g wet tissue and serum ferritin of 5408±2706 ng/mL; while the healthy controls, with both a DXA and a SQUID (n=17), had an average LIC of 251±144. Average aBMD Z-score of the lumbar spine L1-L4 in the Thal group was -2.0 ± 1.1 , the SCD was -2.0 ± 1.6 and the healthy controls: -0.3 ± 0.9. However, when individual vertebrae are analyzed separately, a significant difference was observed between the lumbar spine L1 BMD Z-scores compared to the combined means of L3/L4 Z-scores in the iron loaded population (Table 1). The discrepancy was even greater in subjects with LIC >5000 ug/g wet tissue. These findings were reproduced using heavily iron loaded phantoms. Conclusions Initial results for this study show that there is a relationship between liver iron content and lumbar spine aBMD Z-scores when evaluated by DXA. The BMD Z-score for L1 appears to be more significantly affected by the liver iron content then L2, which was unanticipated. When evaluating patients with liver iron content >3,000 ug/g wet tissue, it is important to consider the effects of iron contribution from the liver on the DXA spine scans and delete L1 and/or L2 from the total Z-score prior to making an interpretation. Failing to do so may under diagnose low bone mass in this at risk patient population. Disclosures: No relevant conflicts of interest to declare.

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Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis – The Value of T2* MRI

Case Reports in Oncology ◽

10.1159/000507756 ◽

2020 ◽

Vol 13 (2) ◽

pp. 712-715

Author(s):

Mustafa A. Al-Tikrity ◽

Mohamed A. Yassin

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

Hereditary Hemochromatosis ◽

Iron Concentration ◽

Hfe Gene ◽

Liver Iron Concentration ◽

C282y Mutation ◽

Liver Iron ◽

T2 Mri

Primary hemochromatosis is an inherited disorder, and the homeostatic iron regulator (HFE) gene C282Y mutation is a common cause of hemochromatosis in Europe. We are reporting a case of a 56-year-old female known to have hemochromatosis with the HFE gene C282Y mutation with a serum ferritin level of 482 μg/L who underwent heart and liver T2* MRI which showed no evidence of iron overload – neither in the heart nor in the liver. This indicates that there is a discrepancy between serum ferritin and liver iron concentration by MRI and the superiority of T2* MRI in diagnosis and follow-up of iron overload in patients with hereditary hemochromatosis.

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Association Between Increased Liver Iron Concentration and Vitamin D Deficiency in Patients with Transfusion Dependent Hemoglobinopathies in British Columbia

Blood ◽

10.1182/blood.v120.21.3203.3203 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3203-3203 ◽

Cited By ~ 2

Author(s):

Hatoon Ezzat ◽

John K. Wu ◽

Heather McCartney ◽

Heather A Leitch

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Calcium Supplementation ◽

Ferritin Level ◽

Iron Concentration ◽

Iron Chelation ◽

Inverse Correlation ◽

Vitamin D Insufficiency ◽

Liver Iron ◽

Clinical Endpoints

Abstract Abstract 3203 Background: Patients with transfusion dependent (TD) hemoglobinopathies are at risk of endocrinopathies and bone disease due to iron overload (IOL). Vitamin D is involved in regulation of calcium homeostasis, bone health and other clinical endpoints. Vitamin D deficiency is a common manifestation of patients with transfusional IOL; the mechanism remains unclear. Vitamin D hydroxylation occurs in the liver; whether liver IOL interferes with this step has not to date been addressed. This study investigates an association between liver iron concentration (LIC) and vitamin D levels in patients with TD hemoglobinopathies. Methods: Patients with TD b thalassemia major (TM), hemoglobin Eb TM (Eβ TM), and congenital dyserythropoetic anaemia (CDA) attending the Inherited Bleeding and Red Blood Cell Disorder Program at the adult (St. Paul's Hospital) or pediatric (BC Children's Hospital) programs in Vancouver, Canada were included if they had an assessment of LIC done by magnetic resonance imaging (MRI) and 25-hydroxyvitamin D3 (25 OH D3) levels between January 2009 and the 31st of December 2011. The analysis was restricted to patients >16 years of age to minimize confounding due to body mass. Clinical data collected included: gender, ethnicity, type of iron chelation therapy (ICT) and vitamin D and calcium supplementation. Laboratory data included: serum ferritin level, 25 OH D3, phosphorus (PO4), ionized calcium (Ca2+), parathyroid hormone (PTH) and thyroid stimulating hormone (TSH). Vitamin D insufficiency was: 25 OH D3 level <75 nmol/L and deficiency <60 nmol/L. Liver and cardiac iron assessment was done by T2* or R2* MRI. Liver iron was: LIC <2 mg/gmDW, normal; 2–5 mg/gmDW, mild; 5.1–7 mg/gmDW, moderate; >7 mg/gmDW severe. Cardiac IOL was: >20 ms, normal; 14–20 ms, mild; 8–15 ms, moderate; <8 ms, severe. Bone mineral density (BMD) was assessed by dual emission X-ray absorptiometry (DEXA) scans of the hip. BMD was: Z score <−1.5, osteopenia; and <−2.0, osteoperosis. Associations between variables were assessed using the Chi-square or Fischer's exact test and the Pearson correlation. Results: 26 patients with TD: βTM, n=21; Eβ TM, n=3; and CDA, n=2 were included, 21 adults and 5 from the pediatric program. Patients characteristics were: median age 24 (range 16–51) years and 11 (42.3%) were male. Ethnicities were: Asian, 11 (42.3%); Indian, 6 (23%); unclear ethnicity, 5 (19.2%); Middle Eastern, 3 (11.5%); and Caucasian, 1 (3.8%). The mean amount of blood received annually was 9633.9 (4677–14,508) mls/year. All patients were receiving ICT: deferasirox (DFX), 16 (61.5%); desferrioxamine (DFO), 8 (30.8%); and combination DFX+DFO, 2 (7.7%). 15 (57.7%) patients received vitamin D and calcium supplementation in variable doses and formulations. Median 25 OH D3 was 66.5 (18–125) nmol/L and vitamin D deficiency/insufficiency occurred in 15 (57.7%) patients: <75 nmol/L, n=15; and <60 nmol/L, n=10. Median Ca2+ was 2.37 (2.2–2.52) mmol/L, PO4 1.21 (0.78–1.71) mmol/L, AST 24.5 (16–46) U/L and ALT 18 (range10–50) U/L; all within normal. Median serum ferritin level was 693.5 (223–3553) mcg/L, LIC 4.25 (1.1–31.8) mg/g dry weight (DW) and median cardiac iron concentration was 35 (13–53.9) ms. Median BMD at the hip was −1.25 (−0.2–−3.7). There was a significant association between LIC >5 mg/gDW, and vitamin D level <60 nmol/L (P= 0.034), with 10 (38.5%) patients having an LIC ≥5 mg/gDW, 5 of whom had a vitamin D level <60 nmol/L. There was an inverse correlation between LIC and vitamin D level, with a Pearson coefficient of −0.33. There was no significant association between: vitamin D level and age, ethnicity, degree of transfusion requirement (DTR), ferritin level or type of ICT; or LIC and age, DTR, ferritin or BMD (P=NS for all). Conclusion: In this single center study of patients with transfusion dependent hemoglobinopathies, we found a significant association between LIC ≥5 mg/gDW and vitamin D level <60 nmol/L, with an inverse correlation between LIC and vitamin D level, suggesting that liver IOL may affect hepatic vitamin D metabolism and result in deficiency. These results warrant verification in larger numbers of patients and prospective trials and investigation of whether vitamin D insufficiency is linked to clinical endpoints. Patients may require intensification of vitamin D supplementation, and/or intensification of iron chelation therapy, particularly if a link to clinical consequences is demonstrated. Disclosures: Ezzat: Novartis: Honoraria. Leitch:Novartis: Honoraria, Speakers Bureau, participated in advisory boards Other.

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Assessing Bone Quality Using Trabecular Bone Score in Patients with Hemoglobinopathies

Blood ◽

10.1182/blood.v128.22.3629.3629 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3629-3629

Author(s):

Melissa Cervantes ◽

Ashutosh Lal ◽

Anne M Marsh ◽

Ellen B. Fung

Keyword(s):

Bone Mass ◽

Bone Quality ◽

Trabecular Bone Score ◽

Iron Concentration ◽

Healthy Controls ◽

Low Bone Mass ◽

Liver Iron Concentration ◽

Mineral Density ◽

Liver Iron ◽

The Relationship

Abstract Introduction: Osteoporosis is characterized by a decrease in bone mass and density with enlarged trabecular space resulting in porosity and bone fragility. It has been described in as many as 70 to 80% of adults with thalassemia (Thal) and sickle cell disease (SCD). Though assessment by DXA scan is now part of routine clinical practice, bone quality has been poorly characterized, particularly in SCD. Trabecular bone score (TBS) is a new textural analysis of lumbar spine DXA scans that reflects bone microarchitecture, shown to be highly predictive of fracture in adults. The objectives of this study were 1) to determine the prevalence of poor bone quality as assessed by TBS in patients with Thal and SCD, compared to healthy individuals and 2) to assess the relationship between bone quality and clinical predictors (age, transfusion status, liver iron concentration, diet, BMI, endocrinopathies). Methods: A retrospective chart review was conducted in patients > 10 years and > 40 Kg with Thal or SCD who had a spine bone mineral density (BMD) scan performed in the previous 5 years. Patients had on average 1.7±0.9 spine scans during the collection period (range 1-5); all scans were reanalyzed using the TBS software (Insight, MediMaps v2.2, France). Optimal bone quality was defined as TBS >1.35; subnormal TBS= 1.34-1.20; abnormal <1.20. Liver iron concentration (LIC) was assessed by SQUID. Data from healthy controls without Thal or SCD were collected from previously completed research studies. Statistical analysis was performed using STATA, v. 9.0 (College Station, TX). This study was approved by the Institutional Review Board at UCSF Benioff Children's Hospital Oakland. Results: Data from 251 patients were abstracted which included, 162 females, 173 adults; 81 Thal, 102 SCD, and 68 healthy controls. Thal patients were older than SCD or controls (29.7 vs. 23.8, 25.8 years, p<0.05) and had lower LIC (2303 vs. 3014 µg Fe/g wet wt., p=0.004) but higher incidence of hypogonadism (31% vs. 1%, p<0.001). No differences were observed in vitamin D status, fracture history or family history of osteoporosis. On average, Thal patients had greater deficits in spine BMD Z-score (-2.1±1.2, Mean±SD), as compared to SCD (-1.0±1.5) and controls (-0.1±0.8), as well as a higher prevalence of abnormal bone quality by TBS (29.7%) vs. 12.2% in SCD, 4.6% in control, (p<0.001). TBS was positively correlated with BMD (r=0.7, p<0.001) and negatively correlated with age (r=-0.28, p<0.001). After controlling for age, BMI, hypogonadism and diagnosis, LIC was negatively associated with bone quality (r=0.30, p=0.001). Conclusions: These data support the relationship between reduced bone mass and bone quality in adult and adolescent patients with hemoglobinopathies. Older patients with low bone mass appear to be at particular risk for abnormal bone quality. TBS may be a valuable clinical tool in the assessment of true fracture risk in this group of patients with extremely low bone mineral density. However, future research is needed to develop models that include BMD and TBS for prediction of absolute fracture risk and need for treatment of low bone mass in patients with hemoglobinopathies. Disclosures No relevant conflicts of interest to declare.

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JADENU® SUBSTITUTING EXJADE® IN IRON OVERLOADED Β- THALASSEMIA MAJOR (BTM) PATIENTS: A PRELIMINARY REPORT OF THE EFFECTS ON THE TOLERABILITY, SERUM FERRITIN LEVEL, LIVER IRON CONCENTRATION AND BIOCHEMICAL PROFILES

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2018.064 ◽

2018 ◽

Vol 10 ◽

pp. e2018064 ◽

Cited By ~ 1

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Iron Concentration ◽

Liver Iron Concentration ◽

Liver Iron ◽

Transfusion Therapy ◽

Biochemical Profiles

Abstract. Introduction: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients withβ-thalasemia major (BMT). The aim of this study was to evalute the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular packed cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade ® therapy (30 mg/kg per day) for 2 years or more before starting Jadenu ® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox ® to Jadenu ® therapy was lack of tolerability, since most of the patients described Deferasirox ® as not palatable. Lab investigations included montly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade ® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC and serum ferritin levels was observed after 1 year of treatment with Jadenu ® . A positive significant correlation was found between serum ferritin level and LIC measured by FerriScan ® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusion: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the long-term outcomes of new deferasirox formulation.

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Association of vitamin D deficiency and bone mass with liver and heart iron overload in transfusion dependent thalassemia

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20202613 ◽

2020 ◽

Vol 7 (7) ◽

pp. 1544

Author(s):

Anjali Verma ◽

Alok Khanna ◽

Babita Jangra ◽

Sanjiv Nanda ◽

Surender Verma

Keyword(s):

Vitamin D ◽

Bone Mass ◽

Iron Overload ◽

Vitamin D Deficiency ◽

Mass Density ◽

Iron Concentration ◽

Bone Mass Density ◽

Liver Iron ◽

Vitamin D Levels ◽

Liver Iron Overload

Background: Transfusion dependent thalassemia patients are reported to have Vitamin D insufficiency/deficiency in many countries. Vitamin D hydroxylation occurs in the liver; whether liver iron overload interferes with this step has not been addressed till date. This study helps to establish an association between liver iron concentration (LIC) and heart iron concentration (MIC) with vitamin D levels and Bone Mass Density in these patients.Methods: A cross sectional study was done by including transfusion dependent Thalassemia patients (TM) if they had an assessment of Liver and cardiac iron done by T2*MRI and bone mineral density by DEXA. Clinical data regarding age, gender, type of iron chelation therapy and laboratory data of S. ferritin and Vitamin D was collected. Data was assessed using appropriate statistical methods.Results: Among 40 TM patients were taken and mean age was 17.6 years. Vitamin D deficiency was identified in 26(65%). 20 out of them had an LIC>7mg/g DW and 6 had MIC>1.65mg/g DW. There was a significant association between LIC>7mg/g and vitamin D level<20 ng/ml and a significant inverse correlation between LIC and vitamin D, suggesting that liver iron overload may indeed affect vitamin D metabolism. Osteopenia was present in 32.5% and osteoporosis was present in 27.5 % of all TM patients. Reduced Bone Mass Density was also found to be linked with iron over load.Conclusions: Regular monitoring of vitamin D levels and supplementation is required in patients with severe liver and heart iron load. More studies are needed to confirm these results.

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Pancreatic MR Imaging and Endocrine Complications in Patients with Beta Thalassemia: A Single Center Experience

10.21203/rs.3.rs-283067/v1 ◽

2021 ◽

Author(s):

Cihangir Sevimli ◽

Yasin Yilmaz ◽

Zuhal Bayramoglu ◽

Rana Gunoz Comert ◽

Nurdan Gul ◽

...

Keyword(s):

Magnetic Resonance ◽

Ferritin Level ◽

Fasting Blood Glucose ◽

Iron Concentration ◽

Threshold Level ◽

Iron Deposition ◽

Beta Thalassemia ◽

Liver Iron ◽

Cardiac Iron ◽

Endocrine Complications

Abstract Iron deposition in various organs can cause endocrine complications in patients with transfusion-dependent beta-thalassemia. The aim was to investigate the relationship between endocrine complications and pancreatic iron overload using magnetic resonance imaging (MRI). Forty patients with transfusion-dependent thalassemia (TDT) were enrolled in the study. The magnetic resonance imagings of the patients were performed using a 1.5 Tesla Philips MRI scanner. Two out of three patients had at least one clinical endocrine complication. The rate of iron deposition was 62.5% in liver, and 45% in pancreas tissue, and was 12.5% in heart tissue. Pancreatic T2* and hepatic T2* values were significantly positively correlated (p = 0.006). Pancreatic T2* and ferritin were significantly negatively correlated (p = 0.03). Cardiac T2* values were negatively correlated with fasting blood glucose (p = 0.03). Patients with short stature had significantly higher cardiac iron burden (22.3 vs. 36.6 T2*ms; p00.01) and patients with hypothyroidism had higher liver iron concentrations (9.9 vs. 6.4 LIC mg/g; p = 0.05). The ferritin level of 841 ng/mL, and liver iron concentration (LIC) value of 8.7 mg/g were detected as the threshold level for severe pancreatic iron burden (AUC 70%, p:0.04, AUC 80%, p = 0.002, respectively). Moreover, males were found to have decreased pancreas T2* values compared with the values in females (T2* 19.3 vs. 29.9, p = 0.05). Patients with higher ferritin levels over than 840 ng/mL should be closely monitored for pancreatic iron deposition, and patients with endocrine complications should be assessed in terms of cardiac iron burden.

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Clinical Features and Morbidities of Hb H Disease in Taiwan

Blood ◽

10.1182/blood.v128.22.4836.4836 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4836-4836

Author(s):

Meng Yao Lu ◽

Ming Chung Kuo ◽

Shih Chung Wang ◽

Shih Hsiang Chen ◽

Bor Sheng Ko ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Clinical Features ◽

Serum Ferritin ◽

Thromboembolic Event ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Globin Gene ◽

Iron Concentration ◽

Hb H Disease ◽

The Mean

Abstract Introduction Patients with non-transfusion-dependent thalassemia experience a wide array of clinical complications despite their independence from frequent, regular red blood cell transfusions. They have the higher incidence of osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, cholelithiasis, thromboembolic disease, pulmonary hypertension, silent cerebral ischemia, and leg ulcers. Thalassemia is highly prevalent in Taiwan and Hb H disease is predominant. But limited data are available about clinical features and morbidities. Here, we studied clinical features and morbidities in Taiwanese patients with Hb H disease. Methods & Results We collected 90 patients with Hb H disease in three hospitals since 2014 Nov till 2016 July. Male to female were 43/59. The mean age was 33.1 years ( from 0.5 to 92.3 years). Two cases died of pulmonary hypertension and old age at 31 years old and 87 years old. Alfa-globin gene genotype studies were done in 44 cases. The (- -(SEA)) type of α(0)-thalassemia mutation was detected in all patients. Twenty- four (57.1%) cases were deletional (α(3.7)/ α(4.2)/unknown 19/4/1) and 20 (42.9%) were nondeletional (CS/RS 18/2) type. The mean of Hemoglobin (Hb) and serum ferritin level were 8.7 g/dL and 730 ng/mL. We also revealed the positive correlation between age and serum ferritin level. The liver iron concentration (LIC) were 6.694 mg Fe/g dw (n=35). The Hb, ferritin and LIC level were not different between deletional and non- deletional groups. They received the transfusion management : 1 with regular transfusion ≦ 6 weeks interval, 5 with irregular transfusion ≧ 6 weeks interval, 27 with occasional transfusion and 57 without transfusion. Fifteen cases received splenectomy. There were significantly higher prevalence for transfusion frequency and splenectomy in non-deletional group. The prevalence of morbidities were 16/79 for cholelithiasis, 12/90 for thromboembolic event, 4/90 for heart failure symptoms ( 2 for pulmonary hypertension), 5/90 for arrhythmia, 3/90 for bone fracture, 5/20 for osteoporosis and 0 for renal stone. There were non-significantly higher prevalence for morbidities in non-deletional group. Discussion & Conclusion The study provides the clinical features and the prevalence of morbidities in Hb H disease in Taiwan. Surprisingly, the prevalence of thromboembolic event and pulmonary hypertension are overlooked in our routine Hb H disease care. We need to schedule close and careful clinical follow up of Hb H patients as they get older, they get some morbidities or they are non-deletional genotype. Disclosures No relevant conflicts of interest to declare.

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Iron Overload Is Under-Recognized and Under-Treated in SCD: A Report from the Grndad Registry

Blood ◽

10.1182/blood-2018-158 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 158-158

Author(s):

Matthew Sears ◽

Sophie Lanzkron ◽

Carolyn Hoppe ◽

Joshua J. Field ◽

Payal C Desai ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Research Funding ◽

Chelation Therapy ◽

Ferritin Level ◽

Research Network ◽

Cell Disease ◽

Liver Iron ◽

High Iron

Abstract Background: Chronic transfusion therapy (CTT) is a mainstay of prophylactic management and treatment for adults and children with high risk Sickle Cell Disease (SCD). We estimate that 10-20% of all adults with SCD managed at our centers, especially those with homozygous HbSS disease, are on CTT, for long-term management of cerebral vasculopathy, significant end organ damage, or chronic pain. Iron overload is a common complication of CTT and for patients receiving intermittent transfusion to treat acute complications. Each unit of transfused blood introduces approximately 250 mg of iron into the bloodstream, and with it, increased oxidative stress (A. Remacha, et al., "Guidelines on haemovigilance of post-transfusional iron overload," Blood Transfusion, vol. 11, no. 1, pp. 128-139, 2013). High iron levels in the blood cumulatively lead to systemic iron deposition, particularly in the liver and heart, and untreated may lead to organ dysfunction or death. Patients with high iron levels should be put on iron chelation. Recent NHLBI guidelines suggest that patients on CTT be monitored for iron accumulation with quarterly ferritin levels, and annual or semiannual liver iron scans to assess hepatic iron burden, though the optimal frequency of these scans has not been established (B. P. Yawn, et al., "Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members," JAMA, vol. 10, no. 312, pp. 1033-1048, 2014). We examined iron overload, its frequency, severity, and management, in a modern population of adults with SCD enrolled in the multi-center prospective sickle cell registry, Globin Research Network of Data and Discovery (GRNDaD). Methods: GRNDaD is a multi-site registry of both adult and pediatric SCD patients, currently accruing at 5 urban sickle cell centers, in Baltimore MD, Cleveland OH, Milwaukee WI, Columbus OH, and Oakland CA. It currently contains prospective baseline and annual update information on nearly 500 people with SCD. Additionally, approximately 150 more patients have consented, with data entry pending. The dataset comprises demographics as well as baseline and yearly lab values, complications, procedures, treatment, and vaccination history for each patient. Among these data are ferritin levels, liver iron scan results, and chelation therapy information. We analyzed ferritin levels in people with SCD, relative to genotype, age, gender, treatment type, liver iron scan results, and chelation therapy history. Results: There were 402 adults (age≥18 years) in GRNDaD who had a non-crisis ferritin level from a routine follow-up visit. This included people with phenotypic homozygous SCD (HbSS, n=255 and Sβ0 thalassemia, N=13), variant SCD (HbSC, n=80, or Sβ+ thalassemia, n=37), and other or unknown genotypes (n=17, Table 1). Nearly 3 in 10 of all patients with SCD (n=118, 29.3%) had a ferritin level at baseline ≥1500 mg/dL, which is an accepted threshold above which to initiate chelation. Most people with an elevated ferritin had phenotypic SCA (homozygous Hb S) (n=111, or 94%). Over half of all SCD patients with a critically elevated ferritin were on CTT (n=64, 54%), and a similar number of people with SCD and critical ferritin levels were on chelation (n=64, 54%). Less than 1 in 4 had had a liver iron scan within 3 years (n=27, 23%). More than 1 in 3 patients with critical ferritin levels and no chelation therapy remained on CTT (n=21, not shown). Conclusions: Our multi-site registry, GRNDaD, prospectively surveyed a sizable population of adults with SCD, including data about iron overload. Of the adults in the GRNDaD registry with iron overload, we identified an unacceptably high fraction, nearly half, who were not on chelation. Most of these patients were people with phenotypic homozygous SCD. We are systematically addressing this deficiency with educational tools through GRNDaD. Since GRNDaD sites are academic centers across the country which focus on the management of SCD, we speculate that the problem of undertreated iron overload nationally is probably both widespread and under-recognized. We anticipate that, as GRNDaD continues to add additional sites, it will evolve as a robust resource through which to highlight important opportunities for clinical quality improvement in the expanding young adult population with SCD. GRNDaD may be a model for identifying and addressing deficiencies in current clinical practices for management of SCD. Disclosures Lanzkron: selexys: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; HRSA: Research Funding; Pfizer: Research Funding; NHLBI: Research Funding; GBT: Research Funding; Prolong: Research Funding. Field:Incyte: Research Funding; Prolong: Research Funding; Ironwood: Consultancy, Research Funding. Desai:University of Pittsburgh: Research Funding; Selexy/Novartis: Research Funding; NIH: Research Funding; Ironwood: Other: Adjudication Committee; FDA: Research Funding; Pfizer: Research Funding. Little:PCORI: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding.

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Supplementation with >Your< Iron Syrup Corrects Iron Status in a Mouse Model of Diet-Induced Iron Deficiency

Biology ◽

10.3390/biology10050357 ◽

2021 ◽

Vol 10 (5) ◽

pp. 357

Author(s):

Tatjana Pirman ◽

Ajda Lenardič ◽

Alenka Nemec Svete ◽

Simon Horvat

Keyword(s):

Iron Deficiency ◽

Mouse Model ◽

Iron Status ◽

Ferritin Level ◽

Control Diet ◽

Iron Concentration ◽

Transferrin Saturation ◽

Food Supplement ◽

Diet Group ◽

Liver Iron

The objective of this study was to compare the effects of >Your< Iron Syrup, a novel oral liquid iron-containing food supplement, with the commonly prescribed iron sulphate (Fe-sulphate) in a mouse model of diet-induced iron deficiency. Standard inbred BALB/cOlaHsd mice were fed low-iron diet for 11 weeks to induce significant decrease in blood haemoglobin and haematocrit and were then supplemented by gavage with either >Your< Iron Syrup or Fe-sulphate for two weeks. In >Your< Iron Syrup group, several markers of iron deficiency, such as serum iron concentration, transferrin saturation and ferritin level were significantly improved in both female and male mice. Fe-sulphate induced similar responses, except that it did not significantly increase iron serum in females and serum ferritin in both sexes. Fe-sulphate significantly increased liver-iron content which >Your< Iron Syrup did not. Transcription of Hamp and selected inflammatory genes in the liver was comparable between the two supplementation groups and with the Control diet group. Some sex-specific effects were noted, which were more pronounced and less variable in males. In conclusion, >Your< Iron Syrup was efficient, comparable and in some parameters superior to Fe-sulphate in improving iron-related parameters without inducing a response of selected liver inflammation markers in a mouse model of diet-induced iron deficiency.

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