9 Anemia in Organ Insult, Systemic Disease & Aging
9.1 CKD Anemia
Pathophysiology: - ↓ EPO (peritubular cells damaged) → major cause - ↓ RBC lifespan, iron restriction (↑ hepcidin), uremia, blood loss - EPO resistance (10%): inflammation, hyperparathyroidism, infection, loss
Iron Management: - Ferritin <100 or TSAT <20% → treat iron deficiency first - Hepcidin ↑ (blocks absorption) despite normal stores - Oral: ferrous sulfate 200–300 mg daily or ferric citrate 210 mg TID - IV: sodium ferric gluconate 125 mg, ferric carboxymaltose 500–1,000 mg, ferumoxytol 510 mg
ESA Options: - Epoetin (IV/SC): 2,000–3,000 u/3 wks - Darbepoetin (IV/SC): 30–60 μg weekly or 500 μg q3wks - Pegylated epoetin (IV/SC): 60 μg q2wks - HIF-PHI oral: roxadustat 70 mg weekly, vadadustat 300 mg daily, daprodustat 2–4 mg daily
Targets & CV Risk: - Goal: Hb 10–12 g/dL (individualize) - Higher targets → ↑ CV events; lower → fatigue & poor QoL - ESA only after iron repleted; lowest dose to avoid transfusion
9.2 Heart Failure Anemia
Epidemiology & Mechanisms: - ~50% ambulatory HF; worse outcomes w/ ↑ severity - ↓ EPO response, blood loss, hemolysis, nutritional deficiency - Iron deficiency (functional or absolute) ~50%: defines as ferritin <100 or TSAT <20%
IV Iron Benefit: - Improves symptoms & exercise capacity even if Hb <13 - Recommended if ferritin <100 or TSAT <20% - Options: sodium ferric gluconate 125 mg, ferric carboxymaltose 500–1,000 mg
Avoid ESA: - ↑ HTN, thrombosis, stroke, cancer - Not routine therapy; IV iron preferred
Assess ferritin & TSAT before therapy. IV iron helps even w/o ↑ Hb.
9.3 Cancer Anemia
Epidemiology & Causes: - ~2/3 anemic at diagnosis or w/ treatment (Hb <12 women, <13 men) - Multifactorial: chemotherapy, blood loss, hemolysis, ↓ EPO, nutrition - Hepcidin dysregulation (upregulated) complicates iron use
Management: - Identify & treat reversible causes (chemotherapy, bleeding) - RBC transfusion standard if symptomatic or severe - ESA + iron → ↑ thrombosis, transfusion need, worse survival - Limited benefit; hepcidin targeting emerging
Standard: transfusion, chemotherapy adjustment, symptom relief. Novel hepcidin therapies evolving.
9.4 Liver & GI Diseases
9.4.1 Liver Disease
Mechanisms: - Underproduction: cirrhosis → marrow suppression, ↓ EPO, nutritional deficit (B₁₂, folate, iron) - Blood loss: varices, portal HTN, coagulopathy - ↑ RBC destruction: hemolysis, ↓ lifespan, microangiopathy - Alcoholic: ↓ B₁₂ absorption, iron overload possible - EPO resistance: low hepcidin in MASLD (appropriate for iron deficiency)
Treatment: - Supportive: optimize liver disease, transfuse if symptomatic & severe - Iron, B₁₂, folate supplementation if deficient - Avoid alcohol & toxins
9.4.2 IBD
Mechanisms: - Most common extraintestinal manifestation: iron deficiency anemia - Chronic GI bleeding, malabsorption, ↑ hepcidin (↓ absorption) - ~90% untreated (impaired absorption + inflammation + loss)
Treatment: - IV iron crucial before anemia correction (oral poorly absorbed w/ inflammation) - Correct IBD, optimize supplementation - Consider infusions if persistent iron deficiency
9.5 COPD Anemia
Epidemiology & Mechanisms: - Prevalence: 7.5–34% - Chronic inflammation, oxidative stress, iron restriction, nutrition, hypoxia - RDW & MCH independent predictors of mortality
Management: - Supportive: optimize pulmonary disease - Correct iron, B₁₂, folate deficiency - Address smoking, nutrition, inflammation when possible - Transfuse only if severe w/ instability or hypoxemia
9.6 Elderly Anemia
Hb Thresholds: - Men: <13 g/dL - Women: <12 g/dL
Causes: - CKD (most common; 50% ≥80 yrs), nutrition (iron, B₁₂, folate) - Occult loss, hemolysis, ↓ bone marrow cellularity, myelodysplasia - Etiology unexplained in ~1/3
Clinical Significance: - Even mild anemia → ↓ cognition, ↓ function, ↑ mortality - Don’t dismiss as “normal aging”
Emerging Therapies: - Hepcidin modulators, HIF agonists, type II receptor agonists entering trials - Screen systematically; correct reversible causes
9.7 References
Anand I, Gupta P. How I treat anemia in heart failure. Blood. 2020;136(7):790–800.
Avasarala S, Kushal R, Demmer T, et al. Prevalence and risk factors of anemia in patients after bariatric surgery in Qassim Region, King Fahad Specialist Hospital. Cancer. 2023;15(6):e41344.
Busetti F, Marchi G, Zidanes AI, Castagni A, Girelli D. Treatments for anemia in the elderly. Transfusion Apheresis Sci. 2019; 58:416–421.
Gafo K, Khodier M, Virig A, Dotujáin G, Dórnnyei G. Anemia of geriatric patients. Physiol Int. 2022;109(2):119–134.
Gilreath JA, Rodgers GM. How I treat cancer-associated anemia. Blood. 2020;136(7):801–813.
Khullar D, Muckula S, Ashshek T. Advancing anemia management in chronic kidney disease: assessing the superiority of darbepoetin alfa over erythropoietin-alpha. Intern Emerg. 2024;16(1):e51613.
Macdougall IC. Anaemia in CKD—treatment standard. Nephrol Dial Transplant. 2024;39(5):770–777.
O’Toole F, Shea R, Reynaud N, McAuliffe FM, Walsh JM. Screening and treatment of iron deficiency anemia in pregnancy: a review and appraisal of current international guidelines. Int J Gynaecol Obstet. 2024;166(1):214–227.
Pan J, Liu M, Huang C, Leng L, Xu Y. Impact of anemia on clinical outcomes in patients with acute heart failure: a systematic review and meta-analysis. Clin Cardiol. 2024;47(2):e2422.
Stein J, Connor S, Virgin G, Eng Hui Ong D, Pereyra L. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol. 2016;22(35):7908–7925.
Tariq S, Ismail D, Thapa M, et al. Chronic obstructive pulmonary disease and its effect on red blood cell indices. Cureus. 2023;15(3):e36100.