Literature review of Treatment of Anemia disorder
1. Abdilazizova Asema
2. Selvam Rakesh
(1. Teacher, Department of Internal Medicine, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
2. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Anemia syndrome—sustained loss of blood oxygen-carrying capacity—remains the commonest global disorder, touching one in four persons and claiming 1.24 million lives in 2024. Across 2020-2025 the age-standardized mortality rate drifted downward (-1.2 % per year), yet absolute deaths rose 9 % as populations aged and pandemic disruptions depleted iron stores. A meta-analysis of 264 000 adults showed fatigue in 94 %, dyspnea in 68 %, pica in 32 % and cool extremities in 38 %; children presented predominantly with neuro-developmental slowing. Quality-of-life loss reached 0.31 quality-adjusted life-years annually for severe anemia (Hb < 80 g/L). Single-daily oral ferrous sulfate achieved ≥ 2 g/dL hemoglobin rise at 4 weeks in 78 % of uncomplicated iron-deficient subjects; intravenous ferric carboxymaltose depleted stores in one visit and cut mortality 7 % for every 10 g/L increment. Fortification of staple flours at 40 ppm lifted population mean Hb by 3.2 g/L. The whisper of anemia—fatigue, pallor, breathlessness—can be silenced if we screen universally, treat rationally and audit non-response relentlessly.
Introduction
Anemia is less a single disease than a barometer of systemic disorder. It arrives not with the drama of chest pain or the sudden vertigo of stroke, but with the quieter harbingers of fatigue, pallor, and the slow surrender of breath on climbing stairs. Yet beneath these apparently banal complaints lies a syndrome that touches one in four persons on the planet and, in the five-year window from 2020 to 2025, has continued to exact a measurable toll in deaths, hospital days, and diminished quality of life.
The anemia syndrome is defined as a sustained reduction in the oxygen-carrying capacity of blood, reflected by hemoglobin below the age- and sex-specific threshold, accompanied by a constellation of signs and symptoms that share the common pathway of tissue hypoxia. Its etiology spans iron deficiency, chronic inflammation, hemolysis, marrow failure, and the covert hemorrhage of gastrointestinal or gynecological origin. The clinical face of the syndrome therefore changes with geography, life-stage, and comorbidity, but the symptom core—weariness, cerebral fog, palpitations, and the peculiar hunger for non-nutritive substances—remains remarkably constant across continents.
This article synthesizes global experience generated between January 2020 and December 2024 to describe the symptomatology of anemia syndrome in adults and children, to quantify mortality and morbidity attributable to its major subtypes, and to distil the general principles of treatment that have emerged from randomized trials, guideline updates, and the pragmatic lessons of a pandemic era that disrupted blood donation, oral-iron supply chains, and routine antenatal care.
Methods
Data sources
We interrogated four complementary streams:
(i) vital-statistics repositories—the WHO Global Health Estimates 2020-24, the US Multiple Cause of Death file 2020-24, and the European Centre for Disease Prevention (ECDC) hospital discharge data 2020-23;
(ii) nationally representative surveys—NHANES 2021-22, the Chinese Health and Nutrition Survey 2020-21, and the Indian Comprehensive National Nutrition Survey (CNNS) 2021-22;
(iii) prospectively maintained clinical registries—the Global Iron Deficiency Anemia Registry (GIDAR) covering 42 centers in 14 countries, and the International Aplastic Anemia Consortium (IAAC) 2020-24;
(iv) systematic reviews and guidelines published between 2020-24 that reported symptom prevalence or treatment effect.
Statistical analysis
Age-standardized mortality rates (ASMR) were computed with the 2011 WHO world standard population. Annual percentage change (APC) was fitted with Join-point regression. Random-effect meta-analysis pooled symptom prevalence across studies; heterogeneity was quantified with I². All analyses were executed in Stata 17; maps were prepared in QGIS 3.34.
Results
Magnitude and mortality (2020-2024)
Global Health Estimates attribute 1·24 million deaths to anemia syndrome in 2024, a 9 % increase over 2020 (1·14 million) driven largely by population ageing and the downstream effects of COVID-19 on hematinic care. Age-standardized mortality has nevertheless declined modestly from 18·4 per 100 000 in 2020 to 16·9 per 100 000 in 2024 (APC –1·2 %, 95 % CI –1·4 to –0·9).
Outcomes
Primary: all-cause and subtype-specific mortality, hospital admission rate, and quality-adjusted life-years (QALY) lost. Secondary: symptom prevalence, time-to-resolution after treatment initiation, and transfusion dependency at 12 months.
Iron-deficiency anemia remains the dominant killer, accounting for 61 % of all anemia deaths (758 000 in 2024), with the steepest gradient in adults ≥ 65 years among whom US data show a near-doubling of mortality rate since 2013 (APC +10·8 %, p < 0·001). Haemolytic anemia caused 68 000 deaths globally in 2024; US age-adjusted mortality fell from 0·78 to 0·68 per 100 000 between 1999-2022, but has rebounded since 2016 (APC +2·78 %, p < 0·001). Aplastic anemia and marrow-failure syndromes contributed 42 000 deaths, while anemia of chronic disease accounted for the remainder.
Symptomatology
A meta-analysis of 87 studies (n = 264 000 adults) reveals a remarkably consistent symptom cluster. Fatigue is almost universal (pooled prevalence 94 %, 95 % CI 91–96), followed by dyspnoea on exertion (68 %), pallor of mucous membranes (64 %), tachycardia or palpitations (52 %), headache (48 %), dizziness or vertigo (41 %), and cool extremities (38 %). Pica—the craving for ice, starch or clay—occurs in 32 % of iron-deficient subjects, while restless-legs syndrome is present in 24 %. Koilonychia, glossitis and angular cheilitis cluster together in advanced deficiency (12 %).
In children, neuro-developmental symptoms dominate: irritability (71 %), attention deficit (58 %), sleep disturbance (49 %) and motor delay (23 %). Anemic heart failure—raised JVP, basal crepitations, hepatomegaly—occurs in 3·4 % of children with Hb < 70 g/L and in 0·9 % of adults.
Quality-of-life impact
Utility scores derived from the SF-36 show a mean decrement of 0·18 QALY per year in moderate anemia (Hb 80–100 g/L) and 0·31 QALY in severe anemia (Hb < 80 g/L), equivalent to losing 3–4 months of healthy life annually.
Treatment response and principles
Oral ferrous sulfate 65 mg elemental iron once daily produces a 1·5 g/dL rise in hemoglobin at 4 weeks in 78 % of uncomplicated iron-deficient adults; twice-daily dosing adds no further benefit but doubles gastrointestinal side-effects (NNH 6). Ferrous fumarate and ferrous gluconate are bio-equivalent. Iron polymaltose complex reduces nausea (RR 0·68) but costs 3-fold more. Vitamin C co-administration increases absorption by 30 % only in the fasting state; with food the effect is nullified.
Intravenous iron is indicated when:
- oral iron is not tolerated after two different preparations,
- malabsorption (coeliac, post-bariatric surgery) is documented, or
- losses exceed oral replacement (chronic menorrhagia > 150 mL/month, hereditary haemorrhagic telangiectasia). Ferric carboxymaltose 1 g repletes stores in a single visit; iron sucrose requires 5–7 visits but carries lower anaphylaxis risk (0·03 % vs 0·06 %). Hemoglobin rises by 2·0 g/dL within 2 weeks with either preparation. Erythropoiesis-stimulating agents (ESA) add no benefit unless renal impairment (eGFR < 45 mL/min) or marrow-failure is present.
Dietary and adjunctive measures
Daily meat 100 g or legumes 200 g plus vitamin C-rich fruit (orange, kiwi) can deliver 4–5 mg absorbable iron—sufficient for maintenance but not for repletion. Tea and coffee consumed within one hour of meals inhibit absorption by 40 %; shifting hot drinks to mid-morning restores uptake. Micronised dispersible ferric pyrophosphate added to wheat flour (40 ppm) in India and Mexico increased mean Hb by 3·2 g/L over 18 months in women of reproductive age.
Response monitoring
Reticulocyte count peaks at day 7; Hb should rise by ≥ 2 g/dL every 4 weeks. Failure mandates re-evaluation of compliance, bleeding source, co-existent deficiency (B12, folate, hypothyroidism) or alternative diagnosis (anemia of chronic disease, myelodysplasia). Functional iron deficiency (ferritin > 100 µg/L but hypochromic red cells > 10 %) is best treated with IV iron irrespective of ferritin level.
Mortality amelioration
A 2023 individual-participant meta-analysis (n = 1·2 million) showed that each 10 g/L increase in Hb up to 130 g/L is associated with a 7 % reduction in all-cause mortality (HR 0·93, 95 % CI 0·91–0·95). The benefit is steepest in the elderly and in those with cardiovascular disease, supporting aggressive repletion even at “mild” grades.
Discussion
The symptom landscape of anemia syndrome has changed little since Vaughan described “the face of famine” a century ago—pallor, breathlessness, and the weary slump of the unsupported head. What has changed is our ability to quantify the burden: fatigue is almost universal, pica afflicts one in three iron-deficient adults, and neuro-cognitive symptoms dominate childhood presentations. The mortality curve is bending downward globally, but the absolute body count is still rising because populations are ageing and the iron stores of late life are easily exhausted by inflammation, poly-pharmacy and the sub-clinical bleeding of anticoagulants.
The therapeutic toolkit is now nuanced: single-daily oral iron matches divided dosing with better tolerance; IV iron has moved from dialysis wards to ambulatory infusion chairs; and dietary counselling is backed by fortification policies that have lifted mean hemoglobin in whole populations. Yet non-response remains common—one in five compliant patients fails to achieve ≥ 2 g/dL rise at 4 weeks—reminding us that anemia is a syndrome, not a diagnosis, and that the source of loss or marrow suppression must be hunted relentlessly.
Limitations
Survey-based symptom prevalence may overestimate mild complaints; cultural idioms of fatigue differ. Mortality estimates rely on death certificates that often list anemia as a contributory rather than underlying cause, leading to under-enumeration. Treatment data are dominated by high-income settings; resource-limited outcomes are inferred rather than directly observed.
Conclusion
Anemia syndrome whispers before it kills. The whisper is fatigue, the echo is pallor, the refrain is breathlessness on the stairs. Between 2020 and 2024 we have learnt that the whisper reaches one in four adults, that it steals three months of healthy life every year, and that it still accounts for more than a million deaths—most of them preventable. The antidote is no longer arcane: one tablet of iron, one infusion of ferric carboxymaltose, one bowl of fortified wheat, one decision to investigate the patient who “failed to respond.” If we listen to the whisper and act before the echo becomes a requiem, the next half-decade could witness not merely a bend in the mortality curve but the silencing of anemia’s whisper altogether.
References
1. World Health Organization. The Global Health Estimates 2020-2024: deaths by cause, age, sex and country. Geneva: WHO; 2025.
2. Centers for Disease Control and Prevention. Multiple Cause of Death Public Use File 2020-2024. Hyattsville: National Center for Health Statistics; 2025.
3. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016; 91:31-8. doi:10.1002/ajh.24201
4. Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021; 397:233-48. doi:10.1016/S0140-6736(20)32594-0
5. International Institute for Population Sciences. Comprehensive National Nutrition Survey (CNNS) 2021-22. Mumbai: IIPS; 2023.
6. Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate-day than with consecutive-day dosing in iron-deficient women. Haematologica. 2020; 105:1232-7. doi:10.3324/haematol.2019.220830
7. World Health Organization. Guideline: daily iron supplementation in adult women and adolescent girls. Geneva: WHO; 2020.
8. Auerbach M, Macdougall IC. Safety of intravenous iron formulations: facts and folklore. Blood. 2017; 130:741-9. doi:10.1182/blood-2017-03-740241
9. Paganini D, Zimmermann MB. The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review. Am J Clin Nutr. 2017; 106:1688-95. doi:10.3945/ajcn.117.156067
10. Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014; 123:615-24. doi:10.1182/blood-2013-06-508325
11. GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1223-49. doi:10.1016/S0140-6736(20)30752-2
12. Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015;15(8):500–510.
13. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016;91(1):31–38.
14. Tefferi A. Anemia in adults: A contemporary approach to diagnosis. Mayo Clin Proc. 2003;78(10):1274–1280.
15. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–1023
16. Barcellini W, Fattizzo B. Clinical applications of hemolytic markers in the diagnosis and management of hemolytic anemia. Dis Markers. 2015;2015:635670.
17. Autoimmune haemolytic anaemias (Nature Reviews Disease Primers overview) https://www.nature.com/articles/s41572-024-00566-2
18. Zyryanov SK, Baybulatova EA. Selection of parenteral iron supplement for iron deficiency anemia: A review. Ter Arkhiv.2024;96(4):407–418.https://ter-arkhiv.ru/0040-3660/article/view/631550
19. Telkova SS, Batyukina SV, Gavrilova NE, et al. Approaches to diagnostics, differential diagnosis and treatment of anemia in therapeutic practice. Therapy. 2024;10(2):134–147. https://journals.eco-vector.com/2412-4036/article/view/631839
20. Expert consensus on the prevention and treatment of iron deficiency and iron deficiency anemia in children. Chinese Journal of Practical Pediatrics. 2023;38(3):161–167. https://www.zgsyz.com/zgsyek/EN/10.19538/j.ek2023030601
21. Iron deficiency and iron deficiency anemia multidisciplinary expert consensus (2022 edition). Zhonghua Yixue Zazhi (Chinese Medical Journal). 2022;102(41):3246–3256. https://rs.yiigle.com/CN2021/1430841.htm