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Article ; Online: How I treat anemia with red blood cell transfusion and iron.

Carson, Jeffrey L / Brittenham, Gary M

2022 Volume 142, Issue 9, Page(s) 777–785

Abstract: ... demonstrated that a restrictive transfusion strategy of 7 to 8 g/dL is as safe as a liberal transfusion ... strategy of 9 to 10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients ...

Abstract	Severe anemia is commonly treated with red blood cell transfusion. Clinical trials have demonstrated that a restrictive transfusion strategy of 7 to 8 g/dL is as safe as a liberal transfusion strategy of 9 to 10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients, including those with preexisting coronary artery disease, acute myocardial infarction, congestive heart failure, and myelodysplastic neoplasms. We present 3 clinical vignettes that highlight the clinical challenges in caring for patients with coronary artery disease with gastrointestinal bleeding, congestive heart failure, or myelodysplastic neoplasms. We emphasize that transfusion practice should be guided by patient symptoms and preferences in conjunction with the patient's hemoglobin concentration. Along with the transfusion decision, evaluation and management of the etiology of the anemia is essential. Iron-restricted erythropoiesis is a common cause of anemia severe enough to be considered for red blood cell transfusion but diagnosis and management of absolute iron deficiency anemia, the anemia of inflammation with functional iron deficiency, or their combination may be problematic. Intravenous iron therapy is generally the treatment of choice for absolute iron deficiency in patients with complex medical disorders, with or without coexisting functional iron deficiency.
MeSH term(s)	Humans ; Iron/therapeutic use ; Erythrocyte Transfusion/adverse effects ; Coronary Artery Disease/complications ; Anemia/etiology ; Anemia/therapy ; Anemia, Iron-Deficiency/complications ; Anemia, Iron-Deficiency/therapy ; Myelodysplastic Syndromes/complications ; Heart Failure/therapy ; Heart Failure/complications ; Neoplasms/complications ; Hemoglobins/analysis
Chemical Substances	Iron (E1UOL152H7) ; Hemoglobins
Language	English
Publishing date	2022-10-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022018521
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Article ; Online: Evaluating growth patterns of abdominal aortic aneurysms among women.

DiLosa, Kathryn / Brittenham, Gregory / Pozolo, Cara / Hedayati, Nasim / Kwong, Mimmie / Maximus, Steven / Humphries, Misty

Journal of vascular surgery

2024

Abstract: Objective: Though initially protected from vessel dilation by estrogen, women may experience rapid abdominal aortic aneurysm (AAA) growth post-menopause. The rate of growth has been poorly defined in prior literature. Here, we describe aneurysm growth ... ...

Abstract	Objective: Though initially protected from vessel dilation by estrogen, women may experience rapid abdominal aortic aneurysm (AAA) growth post-menopause. The rate of growth has been poorly defined in prior literature. Here, we describe aneurysm growth in a cohort of women found through an AAA screening program. Methods: Women with AAAs were retrospectively identified. Aortic imaging was reviewed, and measurements of maximum transverse and anterior-posterior diameters were completed. Growth was stratified by the type of aortic pathology (fusiform aneurysm, aortic ectasia, dissection with aneurysmal degeneration, saccular aneurysm) as well as size category (<3 cm, 3.0-3.9 cm, 4.0-4.9 cm, ≥5.0 cm) at diagnosis. Results: A cohort of 488 women was identified; 286 had multiple scans for review. The mean age of the entire cohort was 75 ± 9.9 years. Stratified by type of pathology, the mean age was 76 ± 8.9 years in patients with a fusiform AAA, 74 ± 9.8 years in ectasia, 65 ± 13.7 years in dissection, and 76 ± 5.6 years in saccular aneurysms. The maximum growth was highest in women with fusiform AAAs, followed by dissection, ectasia, and saccular pathology (9.7 mm, 7.0 mm, 3.0 mm, and 2.2 mm, respectively; P < .001). Comparing mean growth by year, the highest mean growth was in fusiform AAAs (3.6 mm vs 1.75 mm in dissection; P < .001). The Shapiro-Wilk test demonstrated that mean growth per year was non-normally distributed with a right skew. Stratified by aortic diameter at the time of diagnosis, mean growth/year increased with increasing size at diagnosis in fusiform AAAs and dissection (0.91 mm for <3 cm, 2.34 mm for 3.0-3.9 cm, 2.49 mm for 4.0-4.9 mm, and 6.16 mm for ≥5.0 cm in patients with fusiform AAAs vs 0.57 mm, 0.94 mm, 1.87 mm, and 2.66 mm, respectively, for patients with dissection). Smoking history was associated with a higher mean growth/year (2.6 mm vs 3.3 mm; P < .001). Conversely, patients with a family history of AAA had a lower mean growth/year (3.2 mm vs 1.5 mm; P < .001). Conclusions: The rate of aneurysm growth in women varies based on pathology and aneurysm size, and women experience rapid aneurysm growth at sizes greater than 4.5 cm. Current screening guidelines are inadequate, and our results demonstrate that the rate of growth of fusiform aneurysms in women is faster than in men at a smaller size and may warrant more frequent surveillance than current Society for Vascular Surgery recommendations to prevent risk of increased morbidity.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	605700-7
ISSN	1097-6809 ; 0741-5214
ISSN (online)	1097-6809
ISSN	0741-5214
DOI	10.1016/j.jvs.2024.02.042
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Article ; Online: Iron Deficiency in Chronic Pediatric Heart Failure: Overall Assessment and Outcomes in Dilated Cardiomyopathy.

Phillips, Lia / Richmond, Marc / Neunert, Cindy / Jin, Zhezhen / Brittenham, Gary M

The Journal of pediatrics

2023 Volume 263, Page(s) 113721

Abstract: ... reduced to 10.9 ± 1.3 g/dL vs 12.7 ± 2.0 g/dL in iron deficiency and sufficiency, respectively (P = .01 ...

Abstract	Objective: To evaluate the frequency of iron status assessment in pediatric heart failure and the prevalence and adverse effects of absolute iron deficiency in dilated cardiomyopathy-induced heart failure. Study design: We retrospectively reviewed records of children with chronic heart failure at our center between 2010 and 2020. In children with dilated cardiomyopathy, we analyzed baseline cardiac function, hemoglobin level, and subsequent risk of composite adverse events (CAE), including death, heart transplant, ventricular assist device (VAD) placement, and transplant registry listing. Absolute iron deficiency and iron sufficiency were defined as transferrin saturations <20% and ≥30%, respectively; and indeterminant iron status as 20%-29%. Results: Of 799 patients with chronic heart failure, 471 (59%) had no iron-related laboratory measurements. Of 68 children with dilated cardiomyopathy, baseline transferrin saturation, and quantitative left ventricular ejection fraction (LVEF), 33 (49%) and 14 (21%) were iron deficient and sufficient, respectively, and 21 (31%) indeterminant. LVEF was reduced to 23.6 ± 12.1% from 32.9 ± 16.8% in iron deficiency and sufficiency, respectively (P = .04), without a significant difference in hemoglobin. After stratification by New York Heart Association classification, in advanced class IV, hemoglobin was reduced to 10.9 ± 1.3 g/dL vs 12.7 ± 2.0 g/dL in iron deficiency and sufficiency, respectively (P = .01), without a significant difference in LVEF. Conclusions: In this single-center study, iron deficiency was not monitored in most children with chronic heart failure. In pediatric dilated cardiomyopathy-induced heart failure, absolute iron deficiency was prevalent and associated with clinically consequential and possibly correctable decreases in cardiac function and hemoglobin concentration.
MeSH term(s)	Humans ; Child ; Cardiomyopathy, Dilated/complications ; Cardiomyopathy, Dilated/therapy ; Stroke Volume ; Retrospective Studies ; Ventricular Function, Left ; Heart Failure/complications ; Heart Failure/therapy ; Iron Deficiencies ; Iron/pharmacology ; Chronic Disease ; Hemoglobins ; Transferrins/pharmacology
Chemical Substances	Iron (E1UOL152H7) ; Hemoglobins ; Transferrins
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2023.113721
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Article ; Online: Biology of Anemia: A Public Health Perspective.

Brittenham, Gary M / Moir-Meyer, Gemma / Abuga, Kelvin Mokaya / Datta-Mitra, Ananya / Cerami, Carla / Green, Ralph / Pasricha, Sant-Rayn / Atkinson, Sarah H

The Journal of nutrition

2023 Volume 153 Suppl 1, Page(s) S7–S28

Abstract: Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron ... ...

Abstract	Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron deficiency (ID), lack of other micronutrients, infection, inflammation, and genetic conditions. ID develops if the iron circulating in the blood cannot provide the amounts required for red blood cell production and tissue needs. ID anemia develops as iron-limited red blood cell production fails to maintain the hemoglobin concentration above the threshold used to define anemia. Globally, absolute ID (absent or reduced body iron stores that do not meet the need for iron of an individual but may respond to iron supplementation) contributes to only a limited proportion of anemia. Functional ID (adequate or increased iron stores that cannot meet the need for iron because of the effects of infection or inflammation and does not respond to iron supplementation) is frequently responsible for anemia in low- and middle-income countries. Absolute and functional ID may coexist. We highlight continued improvement in understanding the roles of infections and inflammation in causing a large proportion of anemia. Deficiencies of nutrients other than iron are less common but important in some settings. The importance of genetic conditions as causes of anemia depends upon the specific inherited red blood cell abnormalities and their prevalence in the settings examined. From a public health perspective, each setting has a distinctive composition of components underlying the common causes of anemia. We emphasize the coincidence between regions with a high prevalence of anemia attributed to ID (both absolute and functional), those with endemic infections, and those with widespread genetic conditions affecting red blood cells, especially in sub-Saharan Africa and regions in Asia and Oceania.
MeSH term(s)	Humans ; Public Health ; Anemia/epidemiology ; Anemia/etiology ; Iron ; Anemia, Iron-Deficiency ; Iron Deficiencies ; Inflammation/complications ; Biology ; Prevalence
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2023.07.018
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Article: Iron balance in the red blood cell donor.

Brittenham, G M

Developments in biologicals

2005 Volume 120, Page(s) 77–82

Abstract: Phlebotomy of a unit of blood produces a loss of 200 to 250 mg of iron in haemoglobin. Because of physiological differences in iron balance between women of childbearing age and men, the loss of similar amounts of iron at donation has divergent ... ...

Abstract	Phlebotomy of a unit of blood produces a loss of 200 to 250 mg of iron in haemoglobin. Because of physiological differences in iron balance between women of childbearing age and men, the loss of similar amounts of iron at donation has divergent consequences for committed donors. Women of childbearing age have an increased risk of iron deficiency if they donate more than one unit per year while men are usually able to maintain iron balance while donating four or more units of blood per year. Lack of iron is the most important medical reason for deferral from repeat donation and primarily affects women of childbearing age. Deferral of these women discourages them from further donation and may lead to their loss as donors. Provisions for blood donation should protect those who give blood from adverse consequences of their altruism. Safe and effective approaches to iron replacement after donation have been developed that can prevent iron deficiency in women who give blood repeatedly. Blood centres should consider incorporating programmes of iron replacement for women of childbearing age who give blood repeatedly to protect these donors against iron deficiency and to enhance their retention and commitment as dedicated donors.
MeSH term(s)	Anemia/etiology ; Blood Donors ; Erythrocytes ; Female ; Humans ; Infant, Newborn ; Iron/blood ; Male
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2005
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ISSN	1424-6074
ISSN	1424-6074
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Article ; Online: Measurement of the liver iron concentration in transfusional iron overload by MRI R2* and by high-transition-temperature superconducting magnetic susceptometry.

Sheth, Sujit / Allen, Christopher J / Farrell, David E / Tripp, John H / Jafari, Ramin / Wang, Yi / Brittenham, Gary M

Clinical imaging

2019 Volume 55, Page(s) 65–70

Abstract: ... all patients (Pearson's r = 0.91, p < 0.0001) and those with results by susceptometry >7 mg Fe/g liver ... methods were found (0 to <3.2 mg Fe/g liver, dry weight: r = 0.2, p = 0.37; 3.2 to 7 mg Fe/g liver ...

Abstract	Purpose: To compare measurement of the liver iron concentration in patients with transfusional iron overload by magnetic resonance imaging (MRI), using R2, and by magnetic susceptometry, using a new high-transitiontemperature (high-Tc; operating at 77 K, cooled by liquid nitrogen) superconducting magnetic susceptometer. Methods:* In 28 patients with transfusional iron overload, 43 measurements of the liver iron concentration were made by both R2* and high-Tc magnetic susceptometry. Results: Measurements of the liver iron concentration by R2* and high-Tc magnetic susceptometry were significantly correlated when comparing all patients (Pearson's r = 0.91, p < 0.0001) and those with results by susceptometry >7 mg Fe/g liver, dry weight (r = 0.93, p = 0.006). In lower ranges of liver iron, no significant correlations between the two methods were found (0 to <3.2 mg Fe/g liver, dry weight: r = 0.2, p = 0.37; 3.2 to 7 mg Fe/g liver, dry weight: r = 0.41; p = 0.14). Conclusion: The lack of linear correlation between R2* and magnetic susceptibility measurements of the liver iron concentration with minimal or modest iron overload may be due to the effects of fibrosis and other cellular pathology that interfere with R2* but do not appreciably alter magnetic susceptibility.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Erythrocyte Transfusion/adverse effects ; Female ; Humans ; Iron/administration & dosage ; Iron/metabolism ; Iron Overload/etiology ; Iron Overload/metabolism ; Liver/metabolism ; Liver/pathology ; Magnetic Phenomena ; Magnetic Resonance Imaging/methods ; Magnetometry/methods ; Male ; Middle Aged ; Temperature ; Young Adult
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2019-01-31
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	1028123-x
ISSN	1873-4499 ; 0899-7071
ISSN (online)	1873-4499
ISSN	0899-7071
DOI	10.1016/j.clinimag.2019.01.012
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Article: New advances in iron metabolism, iron deficiency, and iron overload.

Brittenham, G M

Current opinion in hematology

1994 Volume 1, Issue 2, Page(s) 101–106

Abstract: Rapid advances were made in understanding the molecular and cellular bases of iron metabolism and its disorders. Molecular mechanisms for the cellular uptake, storage, and utilization of iron were clarified in investigations of the structure and ... ...

Abstract	Rapid advances were made in understanding the molecular and cellular bases of iron metabolism and its disorders. Molecular mechanisms for the cellular uptake, storage, and utilization of iron were clarified in investigations of the structure and functions of transferrin, transferrin receptor, ferritin, erythroid delta-aminolevulinic acid synthase, and the RNA-binding protein termed the iron responsive-element binding protein. Evidence was obtained that a nuclear DNA-binding protein, NF-E2, may be involved in the regulation of both hemoglobin synthesis in erythroid cells and of iron absorption in the intestine. Clinically, progress was made in improving the diagnosis and management of both iron deficiency and iron overload, with studies of the usefulness of serum transferrin receptor measurements, of a new therapeutic preparation of iron using a "gastric delivery system," and of the development of new orally active iron-chelating agents.
MeSH term(s)	Anemia, Iron-Deficiency/epidemiology ; Anemia, Iron-Deficiency/metabolism ; Animals ; Humans ; Iron/deficiency ; Iron/pharmacokinetics ; Iron/physiology ; Iron Chelating Agents/therapeutic use ; Iron Overload/epidemiology ; Iron Overload/metabolism
Chemical Substances	Iron Chelating Agents ; Iron (E1UOL152H7)
Language	English
Publishing date	1994-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
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Article ; Online: Medical laser application: translation into the clinics.

Sroka, Ronald / Stepp, Herbert / Hennig, Georg / Brittenham, Gary M / Rühm, Adrian / Lilge, Lothar

Journal of biomedical optics

2015 Volume 20, Issue 6, Page(s) 61110

Abstract: Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific ... ...

Abstract	Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific requests and potential unmet needs in this multi- and interdisciplinary discipline. Precise gathering of all information on innovative, new, or renewed techniques is necessary to design medical devices for introduction into clinical applications and finally to become established for routine treatment or diagnosis. Five examples of successfully addressed clinical requests are described to show the long-term endurance in developing light-based innovative clinical concepts and devices. Starting from laboratory medicine, a noninvasive approach to detect signals related to iron deficiency is shown. Based upon photosensitization, fluorescence-guided resection had been discovered, opening the door for photodynamic approaches for the treatment of brain cancer. Thermal laser application in the nasal cavity obtained clinical acceptance by the introduction of new laser wavelengths in clinical consciousness. Varicose veins can be treated by innovative endoluminal treatment methods, thus reducing side effects and saving time. Techniques and developments are presented with potential for diagnosis and treatment to improve the clinical situation for the benefit of the patient.
MeSH term(s)	Breast Neoplasms/diagnosis ; Breast Neoplasms/therapy ; Deficiency Diseases/diagnosis ; Female ; Glioblastoma/therapy ; Humans ; Iron/deficiency ; Laser Therapy ; Male ; Photochemotherapy ; Surgical Procedures, Operative ; Tomography, Optical Coherence ; Varicose Veins/therapy
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2015-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.20.6.061110
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Article ; Online: A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being.

Blood

2022 Volume 140, Issue 25, Page(s) 2730–2739

Abstract: ... then randomized to intravenous iron repletion (1 g low-molecular-weight iron dextran) or placebo. A second ...

Abstract	Although altruistic regular blood donors are vital for the blood supply, many become iron deficient from donation-induced iron loss. The effects of blood donation-induced iron deficiency on red cell transfusion quality or donor cognition are unknown. In this double-blind, randomized trial, adult iron-deficient blood donors (n = 79; ferritin < 15 μg/L and zinc protoporphyrin >60 μMol/mol heme) who met donation qualifications were enrolled. A first standard blood donation was followed by the gold-standard measure for red cell storage quality: a 51-chromium posttransfusion red cell recovery study. Donors were then randomized to intravenous iron repletion (1 g low-molecular-weight iron dextran) or placebo. A second donation ∼5 months later was followed by another recovery study. Primary outcome was the within-subject change in posttransfusion recovery. The primary outcome measure of an ancillary study reported here was the National Institutes of Health Toolbox-derived uncorrected standard Cognition Fluid Composite Score. Overall, 983 donors were screened; 110 were iron-deficient, and of these, 39 were randomized to iron repletion and 40 to placebo. Red cell storage quality was unchanged by iron repletion: mean change in posttransfusion recovery was 1.6% (95% confidence interval -0.5 to 3.8) and -0.4% (-2.0 to 1.2) with and without iron, respectively. Iron repletion did not affect any cognition or well-being measures. These data provide evidence that current criteria for blood donation preserve red cell transfusion quality for the recipient and protect adult donors from measurable effects of blood donation-induced iron deficiency on cognition. This trial was registered at www.clinicaltrials.gov as NCT02889133 and NCT02990559.
MeSH term(s)	Adult ; Humans ; Blood Donors ; Iron ; Erythrocytes ; Iron Deficiencies ; Ferritins
Chemical Substances	Iron (E1UOL152H7) ; Ferritins (9007-73-2)
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022017288
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Article: Development of iron-chelating agents for clinical use.

Brittenham, G M

Blood

1992 Volume 80, Issue 3, Page(s) 569–574

MeSH term(s)	Animals ; Deferiprone ; Ferritins/blood ; Humans ; Iron/blood ; Iron/metabolism ; Iron Chelating Agents/adverse effects ; Iron Chelating Agents/pharmacology ; Iron Chelating Agents/therapeutic use ; Pyridones/adverse effects ; Pyridones/pharmacology ; Pyridones/therapeutic use
Chemical Substances	Iron Chelating Agents ; Pyridones ; Deferiprone (2BTY8KH53L) ; Ferritins (9007-73-2) ; Iron (E1UOL152H7)
Language	English
Publishing date	1992-08-01
Publishing country	United States
Document type	Editorial ; Review ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
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