Anemia Flashcards
Conditions that can suppress RBC production
-Renal insufficiency
-Cancer
-Myelodysplasia
-Chronic inflammatory disease
WHO Definition of Anemia
- Hemoglobin level <13 g/dL (males)
- Hemoglobin level <12 g/dL (females
Anemia can be a result of a number of conditions
-Nutritional deficiencies
-Systemic disease
-Bone marrow disease
-Underlying immunologic disorder
-Or when there is something intrinsically wrong with the RBC itself
Normal Erythropoiesis
-Circulating erythrocyte has an average life span of 110-120 days
-More than 90% of the protein content is the oxygen-carrying molecule hemoglobin
-Hemoglobin is made up by four protein molecules or globulin chains that are connected together.
-The normal adult hemoglobin (Hbg) molecule contains two alpha-globulin chains and two beta-globulin chains.
-The globin chains are held together by HEME molecules
-Embedded in the HEME molecule is iron; which gives red blood cell it’s RED COLOR
The most important role of the red blood cell is to
-TRANSPORT OXYGEN FROM THE LUNGS
-To the tissues throughout the body
Erythrocyte maturation
-RBCs are derived from bone marrow where it undergoes 4 different maturation stages until is develops into a reticulocyte (process takes 2-3 days)
-Late maturation stage of the reticulocyte takes place in peripheral blood where it becomes an erythrocyte
Increased Reticulocyte counts
An increased reticulocyte count (or reticulocytosis) is a reflection of the body’s attempt at trying to maintain homeostasis when there is decreased RBC production or shortened life span.
Erythroid specific growth factor-erythropoietin
(EPO)
-Sensed by the juxtaglomerular apparatus of the kidney
-EPO is the primary regulatory hormone for erythropoiesis
-Under normal conditions, RBC mass is nearly constant because of the EPO feedback loop
-When the kidney senses hypoxia, it releases the hormone ERYTHROPOIETIN
-Erythropoietin is the chemical messenger that tells the BONE MAROW to produce more red cells BECAUSE THE BODY IS STARVING FOR OXYGEN
Presenting Symptoms
-Fatigue, weakness, pallor, dizziness
-Dyspnea, tachypnea, O2 desaturation
-Tachycardia, palpitations, hypotension, arrhythmias, chest pain
Physical Exam
-Pallor (usually occurs with hgb <8)
-Confusion, paresthesia
-Tachycardia/Tachypnea
-Systolic murmur
-splenomegaly (hemolysis)
-Orthostatic hypotension
-signs/symptoms of CHF
-Jaundice (hemolysis)
Anemia-Probable etiology
-Poor production of RBC
-Increased RBC destruction
-Blood loss
Poor RBC production
-Nutritional deficits-Folate, iron, B-12
-Bone marrow disorder
-Bone marrow suppression
-Low levels of hormones needed to
stimulate RBC production (EPO, thyroid hormone, androgens)
-Chronic disease/inflammation associated with malignant, infectious, inflammatory disorders
Increased RBC destruction
-Hemolysis
-RBC lifespan is shortened <100 days.
Blood loss-chronic
-Bleeding—loss of RBCs—depletion of iron stores—anemia
Usually occurs with blood loss of:
> 1200 ml for males
> 600 ml for females
Anemia-The Cause
-Classified based upon erythrocyte morphology
-Size, shape, color, inclusions
-CBC, Peripheral blood smear-Morphology, Retic count-bone marrow integrity
Retic Count
Retic count (0.5%-1.5%) shows to be elevated in hemolytic anemia hemorrhage, and Chronic renal failure; decreased in AA, marrow suppression,
CBC
-Hgb-concentration
-HCT-Packed red cell volume-crucial for certain procedures
-RDW-RBC distribution width-measures the RBC size
-MCV (mean corpuscular volume)-average volume of an erythrocyte
-MCH (Mean corpuscular hemoglobin)-average weight (content) of hgb in an average erythrocyte
-MCHC (Mean corpuscular hemoglobin concentration)- (the average concentration of hemoglobin per unit volume of erythrocytes)
Normal values of CBC
-Hgb: Males (12.7-17), Female (11.6-15.6)
-RBC (x 10^12/L): Males (4.0-5.6); Females (3.8-5.2)
-MCV (x 10^12/L): Males (81.2-101.4), Females (81.1-99.8)
-RBC distribution width %: Male (11.8-15.6), Females (11.9-15.5)
-Platelets (x10^9/L): Males (143-332), Female (169-358)
-WBC (x10^9/L); Males (3.6-9.2), Females (3.5-10.8)
Decreased Retic Count
-Bone marrow disease
-B-12 deficiency
-Folate deficiency
-Iron deficiency
Increased Retic Count
-Blood loss
-Hemolytic anemia
-Post-anemia Tx-response
High MCV
-Macrocytic anemia
MCV Normal
Normocytic Anemia
MCV Low
-Microcytic anemia
Microcytic Anemia
-Iron deficiency
-Thalassemia
-Anemia of chronic disease
-Siderblastic anemia
Iron Deficiency Anemia
-Driven by lack of dietary intake, poor absorption by the jejunum, blood loss, blood loss-reproductive women
-10-20 mg/ day of iron to maintain iron demand and iron absorption
-Hgb (low), MCV (low), RDW (high).
-Hypochromic, microcytic pattern on peripheral smear
-Serum ferritin low -Total iron-binding capacity (TIBC)-high -Serum Iron-low
-Chronic blood loss is one of the most common causes of IDA
-always rule out GI bleeding
Serum Ferritin
-Low ferritin is most helpful in distinguishing IDA-no need to check iron studies
Clinical Features of IDA
-Angular cheilosis or stomatitis
-Koilonychia-spoon shaped nails
-Atrophic tongue-glottitis
Treatment: Iron Supplementation
-Elemental iron 2-3 mg/kg daily
(divided in 3 doses)
-Slow-release tablets, 50-100 mg
elemental iron per day
-Ferrous fumarate-325 mg-elemental iron-108 mg
-Ferrous sulfate-325 mg-elemental iron-65mg
-Ferrous gluconate-325mg- elemental iron-35 mg
——First line therapy is oral iron tablets
Iron patient education
-Best absorbed on an acidic environment (avoid PPIs, H2 blockers, antacids)
-Best absorbed in the proximal and third of the duodenum
-Vit C can increase acidity and improve iron absorption
-Iron can reduce absorption of zinc and thyroid supplements
IV Iron
-Iron Dextran: Given as single, large dose
Some patients develop allergic reaction
-Ferumoxytol: Large dose injected over shorter time
2 doses needed; 2nd dose given 3-8 days-510 mg
Less likely to trigger allergic reaction
-Ferric gluconate iron sucrose
10-14 days before you see a response w/ IV iron
Microcytic Anemia Classifications
-IDA
-Thalassemia
-Anemia of chronic disease
Anemia of Chronic Disease: Microcytic anemia
-Inflammatory: RA, SLE, acute hepatitis, chronic hepatitis, malignancies, AIDs, Temporal arteritis
-Organ failure
Anemia of Chronic Disease CBC values & peripheral smear
-CBC: Hgb (low), MCV (normal), MCV low (with severe anemia)
-Peripheral Smear: Normocytic normochromic, microcytic hypochromic (with severe anemia)
Tests for ACD
-Serum ferritin (high)
-TIBC-low
-Serum iron-low-
-ACD is clinically similar to IDA
Acute phase reactants may be elevated
-Fibrinogen
-Sedimentation rate
-CRP
Erythropoiesis Stimulating Agents
-Must demonstrate low erythropoietin level
-Used to treat severely symptomatic anemia in danger of requiring a blood transfusions (hgb levels not >10)
-Used in patients w/ chronic renal failure on dialysis
-Tx cancer associated anemia
-Black box warning-target hgb should be 12 or less. Higher hgb associated with CV and thrombolic events
-Expensive
Thalassemia: Microcytic anemia
-Inherited disorder of hemoglobin synthesis
-Most common genetic diseases in humans
-β-Thalassemia common in Greek and Italian descent
- A-Thalassemia common in African American, American Indian, and Asian groups
-Two main variants-major and minor
Lab findings with Thalassemia
-Hgb (low), MCV (Low).
-Peripheral Smear-Microcytic hypochromic
-Iron studies-normal
-Hgb electrophoresis-Hgb A (elevated B thalassemia), Hgb A2 (normal-alpha thalassemia)
-Order a hgb electrophoresis cascade
Macrocytic Anemia
-Produced by megaloblastic or nonmegaloblastic causes
-Megaloblastic causes impair DNA synthesis in erythrocyte precursors —anemia
Megaloblastic Causes: Macrocytic Anemia
-Vitamin B12 deficiency (cobalamine)
-Folate Deficiency
-Bone Marrow disorders
-Drug induced (anticonvulsant agents, oral contraceptives, chemo, bactrim)
Nonmegaloblastic Anemia
Alcoholism
Bone marrow disorders
COPD
Hypothyroidism
Vitamin B12 Deficiency: Macrocytic Anemia
-Derived from food and animals
-Deficiency with inadequate diet, vegetarianism, impaired absorption
-Absorbed in the terminal ileum
Causes of VB12 Deficiency causes
-Pernicious anemias: most common
-Malabsorption states
-Parasitic infection
-Gastrectomy
-Intestinal disease
Folic Acid Deficiency: Macrocytic Anemia
-Inadequate dietary intake is a common cause of folic acid deficiency
-Folate-Rich Foods-Fruits, green leafy vegetables, peanuts
-High risk groups: Elderly, alcholics, impoverished, malabsorption syndrome (sprue, celiacs)
-Folic acid antagonist-address certain meds that can cause macrocytic anemia
Folic Acid Requirements Increase
-During childhood (growth and development)
-Pregnancy
-Recovery from serious Illness
Tests for macrocytic anemia
-CBC: Hgb (low), MCV (high), RDW (high).
-Peripheral smear: Normochromic Abnormal RBC morphology (anisocytosis, pokilocytosis)
Anisocytosis
Means variation in cell sizes
-Present on peripheral smear in macrocytic anemia
Poikilocytosis
-Variation in the shape of the RBC
-present on peripheral smear with macrocytic anemia
B12 deficiency can cause was neuro defects
-Peripheral neuropathy & lesions in the posterior spinal cord can be seen with untreated B-12 deficiency
Paresthesias & numbness
Loss of vibration & position sense
Sensory ataxia with positive Romberg’s
Limb weakness
Memory loss
Psychosis
B12 deficiency treatment
Injection regimen:
1000 mcg/day IM for five days, then
1000 mcg/week IM for one month, then
1000 mcg/month IM
Oral regimen:
1000 mcg/day
Lifetime treatment required
Folic Acid Deficiency Treatment
Oral regimen:
1 mg - 5mg daily for the first 1-4 months
OR
until a complete hematologic recovery occurs
Normocytic Anemia
-Acute blood loss
-Iron def. or b12 def., folic acid def.
-Hemolytic anemia
-Endocrine disorder (hypothyroid, adrenal insufficiency)
-Bone marrow disease (aplastic anemia, pure RBC aplasia, MDS)
-Anemia of chronic disease
Hemolytic anemias
-Extrinsic and intrinsic factors
-Chemicals (Sulfonamides, penicillin, cephalosporins, EES, acetaminophen)
-Infection (cdiff, e coli, typhoid, malaria, toxoplasmosis, cholera)
-Immune mechanisms (autoimmune anemias)
-Trauma (prosthetic heart valve, arterial grafts, DIC)
-Underlying disease (NHL, CLL, connective tissue disease)
-Structural defects
-Enzyme defects
-Globin synthesis defects (sickle cell anemia)
Hemolysis Labs
-Haptoglobin (low)
-Unconjugated bilirubin (high)
-LDH (high)
-Urine hemoglobin (present)
-Coomb’s test (positive)
-Reticulocytes (high) -bone marrow is trying to compensate for RBC destruction
-Peripheral smear (various inclusions)
