Understanding Anemia: Types, Causes, and RBCs

• Anemia refers to having a Hemoglobin level of < 13g/dL in men, or < 12g/dL in women.
• Alternatively, anemia is a reduction in hemoglobin or circulating red blood cells (RBCs), diminishing the oxygen-carrying capacity

Anemia: Effects & Types

• Impacts quality of life, potentially leading to conditions worsening, like heart failure and cognitive issues
• Common causes include nutritional deficiencies(iron, B12, folate), chronic inflammation/illness, and chronic kidney disease

RBC Development & Destruction

• Red blood cells (RBCs) are created in the bone marrow, with young RBCs (reticulocytes) being released into circulation to mature in about 1 week
• The lifespan of an RBC lasts ~100-120 days
• RBC production is stimulated by erythropoietin (EPO) and cytokines (IL-3, granulocyte-macrophage colony-stimulating unit)
• 90% of EPO is produced by the kidneys so kidney disease can cause drops in EPO, leading to anemia
• Decreased tissue oxygenation signals increased production
• Hemoglobin (Hgb) and iron are incorporated into RBCs during maturation
• Iron is transported to the bone marrow by transferrin protein
• Transferrin receptors increase on cells needing more iron, and transferrin also sends any iron to be stored (ferritin or hemosiderin)
• Hemoglobin has 2 protein chains (α and β), each linked to a heme group with an iron atom at its center
• Vitamin B6, B12, and Folate are needed for heme synthesis and RBC production
• RBCs are broken down via phagocytosis in the spleen and bone marrow; iron and amino acids are recycled
• The liver metabolizes the heme structure to biliverdin, which then becomes bilirubin and is excreted in bile
• Another method of destruction is intravascular hemolysis, where damaged RBCs bind to haptoglobin
• Specific types of anemia include B12 deficiency, Folate deficiency and Iron deficiency

Specific Anemias: Etiology & Pathophysiology

• B12 Deficiency: Gastrectomy, dietary factors, alcohol use, acid suppressing drugs; leading to inadequate intake and impaired absorption
• Folate Deficiency: Drug-induced (azathioprine, methotrexate), dietary factors, leading to inadequate intake and increased utilization
• Iron Deficiency: Dietary factors, menstruation, arteriovenous malformations, GI blood loss, acid-suppressing drugs (PPI, H2); leading to inadequate intake, blood loss or destruction, impaired absorption
• Anemia of Inflammation (AI) or "chronic disease:" Chronic infection or inflammation, critical illness, inflammatory diseases, malignancy; leads to a blunted response to EPO or iron release from cells, shortened RBC life span, and decreased progenitor cell production
• Sickle Cell: Genetic, distortion of red blood cells, leading to increased destruction
• Hemolytic: Drug-induced, leading to increased destruction
• Pernicious: Lack of intrinsic factor, leading to impaired absorption of B12
• Thalassemia: Genetic disorder, leading to impaired production of hemoglobin
• Bone Marrow Suppression: Various causes, leading to decreased production of RBCs
• Chronic Kidney Disease: Kidney dysfunction, leading to decreased erythropoietin production, and elements of AI
• Anemia of the Elderly: Aging; leads to decreased response to EPO, more sensitive to other anemia causes

Diagnosis & Lab Evaluation

• Anemia symptoms vary based on how fast it develops; can include fatigue, pallor, and murmurs
• Testing includes RBC count, hemoglobin level and hematocrit percentage
• RBC indices, including MCV (Mean Corpuscular Volume), can suggest different causes

MCV Values & Implications

• Average RBC size, normal range: 80-97 fL
• High (macrocytic): suggests B12 and/or folate deficiency
• Low (microcytic): suggests iron deficiency or thalassemia
• Normal (normocytic): common in anemia of inflammation/chronic disease
• MCH and MCHC mostly correspond with MCV
• High RDW (Red Cell Distribution Width) can mean there are differences in cell sizes and may mean early iron deficiency or acute anemia

Reticulocytes, Blood Smear & Iron Studies

• Reticulocyte count will increase in acute anemia (e.g. blood loss, hemolysis) if the bone marrow is working
• Reduced retic count means production problems or a chronic anemia
• Peripheral blood smear helps evaluation
• Fecal occult blood test looks for blood loss in the GI
• Iron studies check different types of iron to find cause

Iron Studies: Types & Values

• Serum iron measures iron bound to transferrin, is decreased in iron deficiency, and increased in hemolytic anemias
• TIBC (Total iron binding capacity) shows how many binding sites are free
• Transferrin saturation (Tsat%) compares iron level to TIBC. Tsat% = ([Fe/TIBC] x 100). Normal level is 20-50%
• Ferritin: stored iron; low in iron deficiency
• Transferrin is similar to TIBC and is inversely correlated with ferritin
• Vitamin B12 levels should be tested if macroblastic or high MCV anemia is suspected
• B12 stores in the liver contain 4-5 years worth
• Neurologic signs/symptoms may show before lab values become fully abnormal, look for trend of decreasing B12 as levels stay normal until issue has progressed
• Serum folate and RBC folate may be tested for macrocytic anemia
• Homocysteine & MMA (methylmalonic acid) blood levels may be tested to find deficiencies in B12 and folate
• Consider underlying factors and NSAID use

Treatment & Management: Iron Deficiency Anemia

• Determine and treat underlying cause first
• Supplement diet with iron-rich foods like beef and tofu
• Absorption better from beef and poultry but reduced by dairy and tea
• May take oral iron preparations, taking 150-200mg daily on empty stomach
• Recent studies show less frequent dosing can improve absorption
• Adequate treatment trial/response takes 3-6 months
• For iron deficiency anemia in chronic kidney disease, use non-dialysis: ferric citrate
• It is best absorbed orally in the Fe2+ (ferrous) form and ferrous sulfate is 20-30% elemental iron
• Slow-release and enteric coated preparations are less absorbed and can cause adverse effects like dark feces and nausea
• Avoid drug and food interactions when taking

Parenteral Iron

• IV preparations for when the patient has an intolerance to oral preparations, malabsorption, chronic kidney disease, or refusal to use blood transfusions
• Iron sucrose and Iron dextran may be utilized, or other agents may be considered
• Treatment doses are higher than maintenance (or prophylactic) doses

Monitoring & Treatment: B12 & Folate Deficiencies

• Monitor no sooner than every 2 weeks
• Check iron studies, EPO levels, and occult blood
• Standard regimen for replacement: 1000mcg IM daily x 1 week, weekly x 1 month
• Dietary sources for B12 include fortified breakfast cereal, beef, Sockeye salmon, canned tuna, milk, yogurt, oysters
• POor oral absorption is possible from tablet, food; avoid acid suppression therapy (ASTx)
• Folate is especially key for those with neural tube defects
• For treatment, 1mg PO daily is usually appropriate or 400mcg PO daily recommended for all women of child-bearing age
• Dietary sources include beef, fortified cereals, asparagus, spinach, tomato juice, white rice, oranges, brussel sprouts
• High ferritin (anemia of inflammation) and also check EPO levels because if they are low, give EPO

Anemia of Chronic Kidney Disease (ACKD)

• Initiate treatment with erythropoiesis stimulating agents (ESAs) only when Hgb < 10g/dL to prevent future transfusion of RBCs
• Contraindicated in uncontrolled HTN
• Monitor rise in Hgb and use lowest dose