Approach to and Classification of Anemias

Question 1

define anemia

Answer 1

a decrease in RBC mass; characterized by:

1. decreased RBC count
2. decreased hemoglobin
3. decreased HCT and PCV

Question 2

describe the clinical consequences of anemia

Answer 2

1. reduction in the oxygen carrying capacity of the blood (hypoxemia); can result in hypoxic tissue damage
2. clinical signs due to decreased O2 delivery to tissues
   -lethargy, exercise intolerance
   -plus more clinical signs associated with the l=underlying mechanism
3. clinical manifestations depend on:
   -severity, rate of onset, physical activity, and underlying cause

anemia is a clinical syndrome, NOT a disease or diagnosis!! you MUST ID the underlying cause

Question 3

describe the clinical diagnostic approach to anemia

Answer 3

1. physical exam:
   -pale MM
   -weakness
   -tachycardia
   -pounding pulse
   -heart murmur
   -increased respiratory effort
   -any other clues to cause or underlying disease
2. screen for blood loss with or without coagulopathy:
   -melena, petechia or ecchymoses, epistaxis, hematoma formation, discolored urine (brown or red)
3. check for evidence of organomegaly:
   -could indicate extramedullary hematopoiesis (esp spleen), tumor, hematoma
4. check for lymphadenopathy
5. check for presence of ectoparasites

Question 4

describe the laboratory diagnostic approach to anemia

Answer 4

minimum database! CBC, chem, UA

1. CBC:
   -document and assess anemia severity (RBC, HCT/PCV, Hb)
   -assess if bone marrow is responding (degree of polychromasia, hemoparasites)
   -eval RBC indices (MCH, MCHC)
   -microscopic RBC morphology changes, RBC inclusions, hemoparasites
   -ID plately or leukocyte changes
2. chemistry profile:
   -bilirubin levels
   -organ function and clues to underlying disease
3. urinalysis:
   -more complete eval of renal system
   -screen for hematuria, bilirubinuria, and hemoglobinuria

Question 5

what are the goals of laboratory eval for anemia?

Answer 5

1. determine severity
2. determine is an appropriate bone marrow response is present
3. determine general population
4. determine specific pathophysiologic cause if possible
5. determine additional tests:
   -fecal (parasites), coomb’s (immune-mediated), coag panel, diagnostic imaging, PCR for infectious agents, bone marrow exam tissue biopsy/aspirates

Question 6

describe classification of anemia (broadly)

Answer 6

1. bone marrow response: regenerative vs nonregen
   -regen: increased reticulocytes (if at least 3 days for bone marrow to be able to respond), mod to marked polychromasia, increased MCV, decreased MCHC and RDW (horses rarely release reticulocytes or polychromatophils so use serial CBC)

-nonregen: normocytic, normochromic, RDW normal, MCV and MCHC normal or decreased, decreased RBC production!

2. RBC indices (MCV, MCHC, RDW)
3. underlying mechanism

Question 7

describe eval of bone marrow response to anemia

Answer 7

1. regen versus non regen
   -reticulocyte count used most often (not in horses)
   -polychromasia on blood smear
   -direct bone marrow exam (invasive)
   -serial PCVs/HCT in horses!

if anemia is mild, don’t expect to see a robust increase in reticulocytes and/or polychromasia!

Question 8

describe reticulocytes and polychromatophils

Answer 8

1. if absolute reticulocyte count is > RI = regenerative anemia
   -but production and release of reticulocytes takes 3-5 days!
2. mild polychromasia is normal in HEALTHY dogs
3. slight polychromasia is often present in healthy cats
4. any polychromasia/basophilic stippling in ruminants = regeneration (not much in health so any = significant)
5. horses do NOT release reticulocytes; polychromasia is extremely rare even with severe anemia

Question 9

relate nRBCs to anemia

Answer 9

1. usually metarubricytes but can be earlier stages; rare is okay, but try to correct the WBC count is >5/100 WBCs (rubricytosis)
2. appropriate rubricytosis: intensely regenerative anemia (HELLA increased reticulocytes, marked prolychromasia)
3. inappropriate rubricytosis:
   -nRBCs without reticulocytosis/polychromasia or disproportionate to the regenerative response
   -related to spleen (dysfunction, disease, splenectomy), or bone marrow (neoplasia, damage)

Question 10

describe anemia classification using RBC indices

Answer 10

1. primarily based on MCV and MCHC but these are averages and therefore insensitive in detecting minor changes

MCV: can be microcytic, normocytic, or macrocytic

MCHC: can be hypochromic or normochromic
-hyperchromic does not occur, if present is a cue of free hemoglobin

Question 11

describe normocytic (normal MCV) and normochromic (normal MCHC) anemia

Answer 11

1. most common
2. either non-regenerative anemia or early pre-regenerative anemia or regenerative but insufficient to shift the averages!
   -take RDW, anisocytosis, polychromasia, and reticulocyte count into account before decide regen or not regen

Question 12

describe microcytic (decreased MCV) hypochromic (decreased MCHC) anemia

Answer 12

1. smaller and paler RBCs
2. classic pattern of iron deficiency anemia
3. can sometimes be seen in anemia of inflammatory disease

Question 13

describe macrocytic (increased MCV), hypochromic (decreased MCHC) anemia

Answer 13

1. markedly regenerative anemia
   -reticulocytes are bigger with less hemoglobin than mature RBCs
   -approx 10% of dogs with regen anemia have both and approx 30% have either or
2. lack of this pattern does NOT exclude regeneration

Question 14

describe macrocytic alone (normochromic)

Answer 14

1. regenerative anemia
2. defective erythropoiesis (FeLV in cats)
3. without anemia = congenital in poodles

Question 15

describe hypochromasia alone (normocytic)

Answer 15

uncommon but seen in some regenerative anemias

Question 16

describe microcytic alone (normochromic)

Answer 16

1. early stages of iron deficiency
2. portosystemic shunt
3. without anemia = asian dog breeds (shiba inu, chow chow, akita, shar pei)

Question 17

what are the 3 big categories of classification of anemia by underlying cause?

Answer 17

1. blood/RBC loss/hemorrhage
   -internal or external, typically regenerative anemias
2. increased RBC destruction/hemolysis
   -intra or extravascular; typically regenerative
3. decreased RBC production
   -nonregenerative; typically normocytic, normochromic anemia
   -underlying bone marrow pathology, lack of stimuli (Epo), nutritional deficiencies (iron)

Question 18

describe the 2 types of blood loss anemias

Answer 18

external blood loss:
-GI tract, repro tract, renal losses, blood-sucking ectoparasites
-total loss of protein and cells
-iron is also lost so if chronic, iron deficiency can develop
-regen anemia can become non-regen if not treated

internal blood loss:
-hemorrhage into tissues, peritoneal, or pleural cavity
-erythrocytes and proteins are broken down
-iron is available to reuse
-into cavities: 2/3 of lost RBCs are absorbed within the first 2 days (autotransfusion)

Question 19

describe acute blood loss anemia

Answer 19

1. the severity of lost RBCs will not be appreciated until the lost fluid volume is replaced (24-48hrs) when restored fluid volume dilutes RBCs and proteins
2. it can take 3-5 days to mount a regenerative response so anemia will look non-regenerative initially (pre-regenerative)
3. peak response is 4-7 days

Question 20

describe chronic blood loss anemia

Answer 20

1. small losses over a prolonged period of time; due to
   -internal or external parasitism
   -GI ulcers
   -neoplasia resulting in blood loss (bleeding tumor)
   -hematuria
   -coagulopathis
   -frequent blood draws (esp if tiny animal)
2. you may not detect anemia initially if production matches losses
3. can develop into iron deficiency as iron stores are depleted
   -initially regenerative but with time can progress to non-regen

Question 21

describe RBC destruction in health

Answer 21

1. in health animals approx 1% of RBCs are removed from circulation each day due to normal aging and damage once they have completed their lifespan
2. RBCs are degraded within macrophages
   -iron is recycled
   -hemoglobin is released and metabolized to bilirubin
3. this is a form of extravascular hemolysis but is physiologic
4. hemolytic anemia results if RBCs are destroyed prematurely!! extra or intravascular

Question 22

describe extravascular hemolysis

Answer 22

1. when more unconjugated bilirubin is produced by macrophages than the liver can handle, unconjugated bilirubin builds up in blood, leading to high total bilirubin values
2. also, conjugated bilirubin that builds up in the liver gets regurgitated back into the blood, leading to high conjugated bilirubin, which spills into the urine (bilirubinuria)

Question 23

describe intravascular hemolysis

Answer 23

1. free hemoglobin from IV hemolysis is liberated into the circulation (hemoglobinemia)
2. some of it is taken up by macrophages and hepatocytes and bilirubin is formed
3. most of the free hemoglobin is filtered through the kidneys and excreted in the urine (hemoglobinuria); hemoglobin is toxic to kidneys so yikes

Question 24

compare and contrast extravascular versus intravascular hemolysis

Answer 24

extravascular:
-RBCs are phagocytosed by macrophages (spleen, liver, bone marrow)
-most common!

intravascular:
-RBCs lyse in vasculature
-uncommon but more of a medical emergency

Question 25

describe fragmentation anemia

Answer 25

1. conditions causing increased RBC fragility, often seen with DIC
2. usually only mild anemia or a contributor to anemia