ushapereu anemia9/25/15 2 blood2004;104:22632268 • •data from the third national health and...
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9/25/15
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Approach To The Evalua4on And Management Of Anemia
Usha Perepu, MD Assistant Professor
Hematology/Oncology 9/29/15
Objec4ves
• Defini4on of anemia • Review the causes of anemia • Laboratory evalua4on of anemia • Management
What is Anemia?
• Reduc4on below normal in the mass of red blood cells in the circula4on
• Hemoglobin concentra4on, hematocrit, RBC count
• Men: HGB < 13 g/dL, HCT 40% • Women: HGB < 12.0 g/dL, HCT 35%
Anemia and Volume Status • Hb and HCT are CONCENTRATIONS • Therefore dependent upon plasma volume • Acute bleeds not reflected for 24-‐36 hrs
– Due to volume deficit being slowly repaired via movement of fluid from extravascular to intravascular space
• Anemic pa4ents who are dehydrated will not appear anemic • Pregnant women expand RBCs 25% but plasma volume
increases 50%, producing “physiologic anemia”
Anemia: Special Cases
• Erythrocytosis – People who live at high al4tude have greater RBC volume
– Smokers have increased HCT – impairs the ability of the RBCs to deliver O2
• African-‐American Hbs are 0.5 to 1.0g/dL lower than
Caucasians • Athletes (increased plasma volume, Fe deficiency,
hemolysis, polycythemia, use of performance enhancing agents)
Anemia and the Elderly
• Mul4ple studies show that the elderly do not have a “lower normal range”
• Anemia, while common in the elderly, is s4ll abnormal
• Hb < 13 in males and < 12 in females associated with an increased rela4ve risk of mortality (1.6 and 2.3 respec4vely)
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Blood 2004;104:2263-‐2268
• Data from the Third National Health and Nutrition Examination Survey (1988-1994)
• Prevalence of anemia rises rapidly after age 50, prevalence 20% over age 85
• 11% of men, 10.2% of women over 65 are anemic
• 1/3 due to nutritional deficiency, 1/3 to chronic inflammation or renal disease, 1/3 unexplained
• Most cases mild; only 2.8% of women and 1.6% of men had Hb < 11 g
Ø Unexplained mild “anemia” in elderly people may simply be an effect of aging in some cases
Anemia: History
• Is the pa4ent bleeding? – NSAIDs, ASA – Menstrual history, if applicable (include older women) – Prior intes4nal surgery? – Hx of hemorrhoids, hematochezia, or melena?
• Past medical history of anemia? Family history? • Alcohol, nutri4onal ques4ons • Liver, renal diseases • Ethnicity • Environmental/work toxins (ie lead)
Symptoms of Anemia
• Decreased O2 delivery • Hypovolemia if acute loss • Exer4onal dyspnea, fa4gue, palpita4ons, lightheadedness • Severe: heart failure, angina • “Pica”– craving for clay or paper products • Pagophagia– craving for ice
Signs of Anemia
• Tachycardia, tachypnea, orthostasis • Pallor • Jaundice • Murmur • Koilonychia or “Spoon nails” • Splenomegaly, lymphadenopathy • Petechiae, ecchymoses • Atrophy of tongue papillae • Heme + stool
Red blood cell matura4on Kine4cs Of Erythropoiesis
Hypoprolifera4ve (marrow not working well) Hyperprolifera4ve (marrow working)
Calcula4ng the re4culocyte index will usually tell you which category your pa4ent is in
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Re4culocytes
• Nucleated RBCs – form in marrow where they mature for 3 days and then spend 1 day in circula4on (before maturing to RBC)
• Given avg life span of RBC of 100 days, 1% of RBCs are destroyed each day
• Re4cs form 1% of circula4ng RBCs qd
Re4culocyte response
• Assess adequacy of bone marrow response to anemia • Must adjust for the degree of anemia, use Re4culocyte
Index • RI = (measured re4c %) x (Hct/45) x (1/Correc4on Factor)
– CF: Hct >40 (1); 30-‐40 (1.5); 20-‐29 (2); <20 (2.5) – Reflects increased circula4ng 4me for re4cs as Epo pushes them
out of the marrow earlier
• RI < 2.0 indicates inadequate marrow response
Causes of Anemia
• A kine%c approach, addressing the mechanism(s) responsible for the fall in hemoglobin concentra4on
• A morphologic approach categorizing anemias via altera4ons in red blood cell (RBC) size (i.e., mean corpuscular volume) and the re4culocyte response
Decreased RBC produc4on hypoprolifera4ve anemia( RI low)
• Deficiency of iron, B12, folate • Marrow is dysfunc4onal from myelodysplasia, tumor infiltra4on, aplas4c anemia, etc.
• Bone marrow is suppressed by chemotherapy or radia4on
• Low levels of erythropoie4n, thyroid hormone, or androgens
Increased RBC destruc4on hyperprolifera4ve anemia (RI high)
• RBCs live about 100 days • Acquired: autoimmune hemoly4c anemia, TTP-‐HUS, DIC, malaria
• Inherited: spherocytosis, sickle cell, thalassemia
Blood loss
• Re4c count increase generally less striking than in hemolysis
1. Obvious vs occult 2. Iatrogenic: daily CBC, surgical,
hemodialysis, excessive blood dona4on 3. Menstrual blood loss
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Morphologic approach to anemia Microcy%c anemia ( MCV < 80 fL)
Normocy%c anemia ( MCV 80-‐100 fL)
Macrocy%c anemia (MCV > 100 fL)
Iron deficiency anemia Acute blood loss Alcohol abuse
Thalassemic disorders/ hemoglobinopathies
Iron deficiency (early) Folate, B12 deficiency
Anemia of inflamma4on/chronic disease
Anemia of inflamma4on/chronic disease
Hemoly4c anemia
Sideroblas4c anemia ( congenital, lead, alcohol, drugs)
Bone marrow suppression ( aplas4c anemia, pure red cell aplasia)
Bone marrow disorders such as MDS
Copper deficiency Endocrine dysfunc4on Drugs (chemotherapy agents )
Combined deficiency Liver disease
Other laboratory parameters • RDW: -‐Red blood cell distribu4on width, measures the degree of varia4on of the red cell size -‐If elevated, suggests large variability in sizes of RBCs
• MCH: mean corpuscular Hb -‐Low values are seen in iron deficiency and thalassemia, while increased values occur in macrocytosis of any cause • MCHC: mean corpuscular Hb conc -‐ low values occur in condi4ons that cause low MCV and MCH -‐ increased values occur in spherocytosis and hemoglobinopathies • Are the other cell lines down? -‐ if evidence of leukopenia: consider bone marrow suppression, hypersplenism, B12 deficiency -‐ platelet count: if low may be bone marrow suppression, thrombo4c microangiopathy such as TTP/HUS -‐ high platelet count: myeloprolifera4ve neoplasm, iron deficiency
Blood smear
• RBC size, shape • Polychromasia (young re4cs) • RBC inclusions (nucleated rbc, Howell-‐Jolly bodies, etc) • Rouleaux • Abnormal/immature leukocytes • Platelet number/morphology
Normal Polychromasia
Normal rbc Microcytosis, hypochromia
Microangiopathic hemolytic anemia
Spur cell anemia (liver disease)
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Normal Macrocytic/megaloblastic
Iron Deficiency Anemia
• Iron deficiency affects more than 2 billion people worldwide and iron deficiency anemia remains the top cause of anemia
• Blood loss or decreased absorp4on
are the major causes of iron deficiency
• In determining iron status it is
important to perform iron panel and ferri4n
• Low ferri4n is almost always due to
iron deficiency
Iron deficiency anemia-‐treatment
• Oral iron is inexpensive and effec4ve when taken as prescribed, it can be considered front line therapy
• Oral iron therapy may take upto 6 months to replete stores
• Gastrointes4nal side effects are extremely common and may result in poor adherence to therapy
Iron prepara4ons for Intravenous use
Formula%on Dose per infusion standard
Maximum per single infusion
Iron sucrose ( venofer) 100-‐400 mg 300 mg/ over 2 hrs
Ferumoxytol (Feraheme) 510 mg over 1 min 510-‐1020 mg over 15-‐60 min
Ferric carboxymaltose ( Injectafer)
750-‐1000 mg over 15-‐30 min
750-‐1000 mg over 15-‐30 min
Total iron deficit = Body weight [kg] x (Target Hb – Actual Hb) [g/l] x 2.4 + Iron stores [mg] 500 mg iron for iron stores is recommended if the body weight is above 35 kg.
Anemia of Renal Insufficiency
• Unremarkable peripheral blood smear • Inappropriately normal erythropoie4n level • Anemia usually severe and symptoma4c when Cr > 3.0 • Mild to moderate anemia found in Cr 1.5-‐3.0 • Tx: Epogen or similar, Fe (oral, IV) if iron stores are found
to be low
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Anemia of Chronic Disease
• Thought to be a cytokine mediated process which inhibits red blood cell produc4on or interferes with ac4on of erythropoie4n – Therefore, the disease needs to be inflammatory
• Decreased iron u4liza4on/mobiliza4on • Seen with rheumatologic diseases, chronic infec4ons, malignancy • Indices: Low Fe, Low TIBC, N/increased Ferri4n • May be seen in conjunc4on with Fe-‐deficiency
Folate and B12
• Serum folate usually sufficient, but if folate level is normal but folate deficiency is suspected, check serum homocysteine (elevated because of impaired folate dependent conversion of homocysteine to methionine) or RBC-‐folate
• When B12 is slightly low– a
more sensi4ve and specific test is serum methylmalonic acid level, will be increased if B12 is truly low
Evalua4on of Hemolysis
• LDH: increases • Indirect bilirubin increases
(increased Hb catabolism) • Haptoglobin decreases • Re4culocyte count increases • Urine hemosiderin test = present
in intravascular, absent in extravascular hemolysis!
• Coombs test:
– (+) = immune – (-‐) non immune
Hemoly4c Anemia
Immune • Autoimmune hemoly4c
anemia -‐ Warm -‐ Cold • Alloimmune -‐ Hemoly4c disease of
newborn -‐ Incompa4ble blood
transfusion • Drug Induced
Non immune • Microangiopathic hemoly4c
anemia ( TTP, HUS) • Trauma: prosthe4c valves,
burns, exercise • Infec4on: malaria • RBC membrane defects • Enzyme defects • Hemoglobinopathy • Paroxysmal nocturnal
hemoglobinuria
Indica4ons For Bone Marrow Biopsy
• Re4c index not appropriately increased • No evidence of iron/B-‐12/folate deficiency, renal failure,
endocrinopathy, inflamma4on or other low EPO state • Poor response to EPO, iron or vitamin replacement • WBC/diff/ Plt abnormal, monoclonal gammopathy, or
other peripheral blood evidence of marrow disorder Would you treat leukemia/MDS or other neoplas4c
disorder if you found it?
Approach to Anemia CBC
Reticulocyte count MCV
RI < 2% RI > 2%
Underproduction Increased destruction or loss
MCV < 80 Microcytic
MCV > 100 Macrocytic
MCV 81 – 99 Normocytic
MCV Further work up Based on history, Physical, other
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Anemia: Summary
• ANEMIA IS NEVER NORMAL • Determine if ACUTE or CHRONIC • Consider the e4ology • CALCULATE the RETIC INDEX • Look at the smear • Consider the e4ology based on rbc morphology and laboratory studies
• Treat appropriately
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