Anemia Flashcards
Define Anemia
A decrease in the circulating RBC mass, with a reduction in one or more of the major RBC measurements:
• RBC count
• Hemoglobin (Hb) concentration
• Hematocrit (Hct): % RBC
Normal ranges for Hb and Hct
Varies but usually Hb:Hct is 1:3
For Males:
Hb 14-18 g/dL
Hct 40-50%
For Females:
Hb 12-16 g/dL
Hct 35-45%
Anemia is defined as Hb<14 in men, <12 in women
Populations for which the normal ranges of Hb/Hct don’t usually apply
Athletes People living at high altitude Smokers African-Americans Chronic disease Older adults
What are reticulocytes and what does the reticulocyte count tell us?
Immature RBCs —> mature RBCs
• spend about 3 days in bone marrow, 1 day in peripheral blood
RBC life-span ~120 days - old RBCs are primarily removed by the spleen
Reticulocyte count (“retic”) can detect abnormalities with bone marrow (should be elevated following blood loss)
Normal retic count = 0.5-2%
Recognizing reticulocytes on a peripheral smear
“Lots of blue means lots of new” - polychromasia (lots of different colors)
Reticulocytes are larger than mature RBCs, lack central pallor (because not yet concave)
Causes of anemia
Decreased RBC production
• Nutritional deficiencies (Iron deficiency, B12/folate deficiency), chronic disease, ineffective erythropoiesis
Increased RBC destruction
• Hemolysis (hemolytic Anemia, malaria)
Blood loss
• Menstrual, GI, trauma
Mean Corpuscular Volume (MCV)
Calculated value to determine average volume (size) of RBCs
Microcytic —> MCV < 80fL
Normocytic —> MCV 80-100fL***
Macrocytic —> MCV >100fL
Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC)
Reflect the amount of hemoglobin in RBCs
MCH = avg hemoglobin content MCHC = avg hemoglobin concentration
Low MCH = hypochromic (pale on smear b/c low Hb)
High MCH = hyperchromic
MCH/MCHC usually “follow” MCV
• “Microcytic hypochromic” anemia
Red Cell Distribution Width (RDW)
A measure of the variation in RBC size (normal = 11-15%
Measured by machine
“Anisocytosis” = variation in size of RBCs
Helpful in DDx
Signs and Symptoms of Anemia
Fatigue/weakness Headache Dizziness, Dyspnea, Palpitations (due to cardiac compromise) Pallor Heme+ stool Orthostatic changes Tachycardia
Acute, abrupt onset - may have Sx with relatively mild anemia
Chronic, insidious onset - Sx may not appear until Hb <7-8 g/dL
Three main categories of Anemia
Microcytic hypochromic
• Iron deficiency, thalassemia, sideroblastic anemia
Normocytic, normochromic
• Hypothyroidism, liver disease, chronic disease
Macrocytic (megaloblastic)
• Folate deficiency and vitamin B12 deficiency
Iron Deficiency Anemia
Most common microcytic anemia
Major causes:
• Blood loss (most common cause of iron def in adults in resource rich countries)
• Decreased dietary intake
• Decreased iron absorption (celiac disease, bariatric surgery, H. pylori infection)
Dx study results for iron deficiency anemia
Low RBC, H/H
Microcytic, hypochromic
-MCV sometimes normal in early IDA b/c we deplete our iron stores first before we take it out of circulation
Iron studies:
• Low ferritin (stored iron)
• Low serum Fe
• High TIBC (total iron binding capacity) - we have less so we have more capacity to take it up
Increased RDW (variations in cell size)
Retic count may be low or inappropriately normal
Other clinical manifestations of iron deficiency anemia (besides blood counts etc)
Gloss it is, angular ceilings, koilonychia (spoon nails)
Pica (craving for ice, clay, dust)
Dysphasia (esophageal webs) - Plummer-Vinson syndrome
Restless legs syndrome
Why is it important to identify the underlying cause of iron deficiency anemia?
To rule out occult malignancy
Consider referral for endoscopic and/or radio graphic testing, esp if not woman of child-bearing age
Treatment for iron deficiency anemia
Treat underlying cause
Replace iron stores
• Orally: ferrous sulfate 325 mg BID-TID (must take on an acidic stomach); appropriate response = Hct 1/2 way to normal in 3 weeks, full return in 2 months; continue for 3-6 months after anemia has corrected to replenish stores
• Parenteral iron for select patients (chronic kidney disease - problem of absorption)
Blood transfusions (select patients - not recommended for iron replacement)
Define thalassemia
Inherited hemoglobinopathy —> reduction in the synthesis of globin chains (alpha or beta)
Highest prevalence in parts of Africa, Asia, and the Mediterranean
Leads to ineffective erythropoiesis and hemolysis
Result: variable degrees of anemia and extramedullary hematopoiesis
Can cause bone changes, impaired growth, and iron overload
Different types of Alpha Thalassema
Selection of one or more of the four alpha-globin chains
1 Deletion —> Silent carrier (aa/a-) no symptoms
2 Deletions —> Alpha-thalassemia minor (aa/- -), mild Microcytic anemia
3 Deletions —> Hemoglobin H disease (a-/- -), moderate microcytic anemia (chronic hemolytic anemia)
4 Deletions —> Hydrops fetalis (- -/- -) usually fatal in utero
Different types of Beta-Thalassemia
Due to reduced or absent beta-globin chain synthesis, usually a point mutation rather than gene deletion
Thalassemia Minor (Trait) • Dysfunction of one ß-globin chain • Asymptomatic or mild microcytic anemia (abnormal labs but no Sx)
Thalassemia Intermedia
• Less severe phenotype than Thalassemia Major
• Non-transfusion dependent
• Chronic hemolytic anemia
Thalassemia Major • Dysfunction of BOTH ß-globin chains • Transfusion-dependent • Severe hemolytic anemia • If untreated, 85% of children will die w/in the first 5 years
Lab evaluation for Dx of Thalassemias
Normal to increased RBC MCV is strikingly low (<75 fL) RDW is NORMAL Retic count variably increased Normal to increased ferritin and iron (can have overload) Normal to decreased TIBC
***Hemoglobin Electrophoresis - helps with Dx, detects the type of hemoglobin present
Tx of Thalassemia
Tailored to severity of disease
Folic acid supplementation (b/c needed for erythropoiesis in chronic hemolysis)
AVOID IRON SUPPLEMENTS!
Regular transfusion schedule if severe
May also require iron chelation therapy or splenectomy
Hematopoietic cell transplantation for severe beta thalassemia
Genetic counseling
Sideroblastic Anemia
Hereditary or acquired RBC disorder
Abnormal RBC iron metabolism —> dismissed heme synthesis —> iron accumulation in cells
Hallmark sign of sideroblastic anemia
Ring sideroblasts in bone marrow aspirate (blue-stained iron rings around cells)
May also see siderocytes with Pappenheimer bodies on peripheral smear (reflection of iron accumulation
Causes of sideroblastic anemia
In adults, acquired is more common
Often a variant of myelodysplastic syndrome (MDS)
Other causes:
• Chronic alcoholism
• Medications
• Copper deficiency
Diagnostic Studies for Sideroblastic Anemia
Bone marrow aspirate (***Ring sideroblasts)
MCV - low, normal, or slightly increased (varies)
Elevated RDW
Normal to low retic count
Normal or elevated ferritin
SYSTEMIC IRON OVERLOAD (b/c increased absorption from gut)
• May be indistinguishable from hereditary hemochromatosis
• May lead to irreversible organ damage
Treatment for Sideroblastic Anemia
Pt Ed and referral to hematology Treat underlying cause Discontinue offending drugs Removal of toxic agents Pyridoxine (vitamin B6) - contributes to hemoglobin synthesis Transfusion/management of iron overload
Anemia of Chronic Disease (ACD)
Second most common cause of anemia worldwide (after iron deficiency)
Common chronic systemic diseases • Inflammatory diseases • Rheumatologic disorders •Malignancy • Chronic infection • Organ failure • Anemia of older adults
Pathogenesis for Anemia of Chronic Disease
Hepcidin-induced alterations in iron metabolism
Hepcidin = key regulator of the entry of iron into circulation (traps iron); high levels seen with inflammation —> iron trapping within macrophages and decreased gut iron absorption
Inability to increase erythropoiesis (esp in older populations)
Impaired EPO production (kidney disease)
