Evaluation of Erythrocytes: Anemia and Regeneration

Question 1

What important information from a history can help you diagnose the cause of an anemia?

Answer 1

prior drug administration exposure to toxic chemicals or plants family or herd occurrence recent transfusion or colostrum ingestion age at onset of anemia

Question 2

Physical findings associated with anemia

Answer 2

pale MM weakness, loss of stamina, exercise intolerance tachycardia and tachypnea, esp. after exercise cardiac murmur secondary to increased blood turbulence shock if rapid severe hemorrhage occurs icterus, hemoglobinuria, hemorrhage, or fever - depending on dz present

Question 3

Normal HCT with low TPP leads you to what DDX?

Answer 3

GI protein loss proteinuria liver dz

Question 4

Normal HCT with high TPP leads you to what DDX?

Answer 4

increased globulin synthesis dehydration masked anemia

Question 5

High HCT with low TPP leads you to what conclusion?

Answer 5

protein loss combined with relative or absolute erythrocytosis

Question 6

High HCT + High TPP = ?

Answer 6

dehydration

Question 7

Low HCT + low TPP =?

Answer 7

substantial ongoing or recent blood loss, overhydration

Question 8

High HCT + normal TPP =

Answer 8

splenic contraction absolute erythrocytosis dehydration masked hypoproteinemia

Question 9

low HCT + normal TPP =

Answer 9

increased erythrocyte destruction, decreased erythrocyte production, chronic hemorrhage

Question 10

low HCT + high TPP =

Answer 10

anemia of inflammatory dz multiple myeloma lymphoproliferative dz

Question 11

How do you classify an anemia as regenerative or non regenerative?

Answer 11

absolute reticulocyte count increased increased polychromasia on blood film marrow evaluation

Question 12

What are the size and color classifications of anemia?

Answer 12

microcytic (MCV below reference), normocytic (MCV in reference), macrocytic (MCV above reference) hypochromic (MCHC below reference), normochromic (NO hyperchromic)

Question 13

T/F hemodilution is a true anemia

Answer 13

F

Question 14

T/F severity can rule in or out a specific cause of anemia

Answer 14

T - ie. severe anemia should not be attributed alone to anemia of inflammatory disease

Question 15

What are the four pathophysiologic mechanisms of anemia?

Answer 15

blood loss or hemorrhage accelerated erythrocyte destruction (hemolysis) reduced/defective erythropoiesis hemodilution (not really an anemia)

Question 16

Hemodilution “anemia”

Answer 16

expansion of vascular space - pregnancy, growth (plasma volume expansion, dilution from colostrum, destruction of fetal RBCs, decreased production of erythropoietin in first few months of life) overhydration splenic sequestration - splenomegaly, anesthesia, heparin treatment in horses

Question 17

Which species is not ideal for a bone marrow evaluation?

Answer 17

Horses

Question 18

What does regenerative anemia look like on blood films?

Answer 18

increased polychromasia increased anisocytosis metarubricytosis increased howell-jolly bodies basophilic stippling ONLY increased polychromasia is a valid indicator of regeneration - all else associated with but not indicator

Question 19

Why would an acute hemorrhagic or hemolytic anemia initially appear non-regenerative?

Answer 19

because it takes bone marrow 3-5 days to respond to an anemia

Question 20

What are features that may be seen in blood smears as part of the regenerative response but are not specific for regeneration?

Answer 20

anisocytosis increased numbers of nucleated RBCs basophilic stippling (aggregates of ribosomes and polyribosomes, especially seen in ruminants but can also be seen in dogs and cats) increased numbers of RBC containing Howell-Jolly bodies (remnants of the nucleus)

Question 21

How does MCV change in a regenerative response to anemia?

Answer 21

within reference range early (takes 3-4 days for bone marrow to respond), then highest in hemolytic anemia (spherocytes from phagocytosis by macrophages and polychromatophils from regeneration) ***may be low with chronic blood loss

Question 22

What does the MCHC look like in a regenerative anemia?

Answer 22

within reference range early low with a high percentage of reticulocytes, especially “stress reticulocytes”=released early from BM

Question 23

Clinical signs of hemolytic anemia

Answer 23

depends on severity and speed of onset icterus may be present if rapid RBC destruction red plasma hemoglobinuria (if intravascular hemolysis present)

Question 24

Laboratory findings of hemolytic anemia

Answer 24

reticulocyte counts higher than external hemorrhage plasma protein concentration normal or increased leukocytosis with neutrophilia and monocytosis bilirubinemia, hemoglobinemia, +/-hemoglobinuria abnormal erythrocyte morphology (ie. heinz bodies, poikilocytes, spherocytes, parasites)

Question 25

Extravascular hemolysis often occurs in which organs?

Answer 25

spleen, liver, bone marrow

Question 26

Which is acute or chronic - extravascular hemolysis or intravascular hemolysis?

Answer 26

Extravascular - can be either intravascular - often rapid - per acute or acute

Question 27

DIC occurs as a result of ________ (extravascular/intravascular) hemolysis.

Answer 27

both can cause DIC

Question 28

Which has a worse prognosis intravascular or extravascular hemolysis?

Answer 28

intravascular - abnormal location for RBC destruction, usually rapid, not an isolated environment = fragments are a risk for DIC and anaphylactic shock

Question 29

What is the pathological mechanism that causes hemoglobinuria?

Answer 29

lysed RBCs free Hgb into bloodstream - transport protein binds and it is taken to liver for metabolism and recycling. transport capacity is overwhelmed if destruction is rapid and/or severe enough - left over circulating Hgb is excreted in the urine

Question 30

Where does bilirubin back up to first (if RBC destruction too rapid/severe to be excreted via normal mechanisms)?

Answer 30

backs up to urine and feces first = bilirubinuria then backs up in plasma = bilirubinemia then backs up to mucocutaneous tissues = icterus

Question 31

Which of the following conditions distinguish intravascular from extravascular hemolysis? bilirubinuria bilirubinemia hemoglobinuria hemoglobinemia

Answer 31

hemoglobinemia hemoglobinuria

Question 32

Name some causes of hemolytic anemias.

Answer 32

* immune-mediated * hemoparasites * infectious agents * chemicals and plants * fragmentation * hypoosmolality * hypophosphatemia * hereditary RBC defects

Question 33

What are some of the causes of immune-mediated erythrocyte destruction?

Answer 33

IMHA (mostly dogs) neonatal isoerythrolysis (mostly horses and cats) lupus erythematosus (dogs) incompatible blood transfusion penicillin and sulfonamides (horses) cephalosporins, levamisole, primicarb insecticide (dogs) propylthiouracil, and possible griseofulvin, albendazole (cats)

Question 34

Describe the pathological mechanism of IMHA.

Answer 34

attachment of IgG or IgM causes fixation of complement to RBC membranes - Macrophages phagocytize them - forms spherocytes

Question 35

How can you detect IMHA in a dog?

Answer 35

Coombs test - but be careful because false positives and negatives do occur

Question 36

Name three erythrocyte parasites.

Answer 36

anaplasma (ruminants) mycoplasma (not in horses) babesia cytauxzoon felis (non regenerative) theileria (ruminants and horses)

Question 37

Name some infectious agents that cause IMHA.

Answer 37

leptospira and clostridium (primarily ruminants and horses) FeLV (decreases RBC production mostly) EIA virus (acute stage of infection = "coggins") Sarcocystis species (cattle and sheep) trypanosoma (not imp. in US)

Question 38

Name two chemicals/plants that can cause anemia.

Answer 38

Question 39

Name two causes of hypoosmolality.

Answer 39

hypotonic fluid administration - IV or oral water intoxication

Question 40

Name two causes of hypophosphatemia.

Answer 40

decreased RBC ATP concentration postparturient hemoglobinuria ketoacidotic diabetes mellitus following insulin therapy (cats and dogs) hepatic lipidosis (cats) hyperalimentation (dogs and cats)

Question 41

Miscellaneous hemolytic anemias

Answer 41

liver failure in horses splenic torsion in dogs selenium deficiency in cattle grazing on st. augustine grass postparturient hemoglobinuria in cattle not associated with hypophospatemia

Question 42

Causes of blood loss anemia

Answer 42

trauma blood sucking parasites coagulation disorders neoplasia GI ulcers inflammatory bowel diseases

Question 43

Distinguish between external and internal hemorrhage

Answer 43

External - erythrocytes, plasma, proteins and iron are lost to the world or a parasite; decreased PCV and TP Internal - iron is conserved, some erythrocytes and plasma proteins may be reabsorbed from body cavities, slight hyperbilirubinemia may occur; decreased PCV and increased TP

Question 44

Causes of acute hemorrhage

Answer 44

trauma recent surgery bleeding ulcers bleeding tumors (esp. hemangiosarcoma) severely marked decrease in platelets (thrombocytopenia usually less than 25k/microliter) inherited or acquired coagulopathies

Question 45

Acute hemorrhage laboratory findings

Answer 45

usually does not cause appreciable thrombocytopenia hematocrit is variable depending on time after hemorrhage plasma protein concentration variable based on time after hemorrhage - initial probably unchanged, shifts start few hours post and continue for 2-3 days - **decreased PCV and TP 12-24 hours after blood loss as a result of dilution by interstial fluid**; TP will return to normal in about a week unless ongoing loss in 3 days retics appear in blood, peak at 7-10 days

Question 46

How can a chronic blood loss cause a non-regenerative anemia?

Answer 46

if severe iron deficiency develops

Question 47

Lab findings of chronic blood loss

Answer 47

hypoproteinemia - if hemorrhage is ongoing can be regenerative or non-regenerative microcytic hypochromic if iron deficient thrombocytosis (seen in 50% of cases) fragmentation morphologies due to thin cells being produced

Question 48

Describe the mechanism of the development of iron deficiency anemia.

Answer 48

decreased bone marrow iron since iron used to maintain erythropoiesis iron stores absent - RBCs produced without iron -\> iron deficiency anemia characterized by microcytosis and hypochromasia

Question 49

Causes of iron deficiency anemia

Answer 49

dietary deficiency of iron (can be secondary to acidosis, excess vitamin C, or excess zinc) copper deficiency (necessary for absorption of iron from GI and release of iron from stores in macrophages in the body; seen in ruminants) chronic external blood loss - ie. bleeding ulcers, flea infestation

Question 50

Name causes of a macrocytic anemia.

Answer 50

FeLV infection in cats myeloproliferative disorders folate deficiency dyserythropoiesis

Question 51

What are some causes of non-regenerative anemias?

Answer 51

* Reduced erythropoiesis * chronic renal disease - decreased EPO, RBC lifespan * hormone deficiencies - ie. hypothyroid dogs * anemia of inflammatory dz * cytotoxic damage to bone marrow (chemo) * infectious agents * immune mediated * myelophthis * Defective erythropoiesis - disorders of heme/nucleic acid synthesis, abnormal erythroid maturation

Question 52

What are the causes of anemia from chronic renal dz?

Answer 52

**decreased erythropoietin production** (=main mechanism) supression of erythropoiesis by uremic toxins decreased RBC lifespans - uremic toxins kill via extravascular hemolysis hemorrhage - often have oral and GI ulcers due to uremia

Question 53

Non regenerative anemias due to endocrine disorders produce what type of anemia?

Answer 53

moderate normocytic normochromic not associated with poikilocytosis

Question 54

Describe the pathogenesis of anemia of chronic inflammatory dz.

Answer 54

cytokines - inhibition of erythroid progenitor cells, insufficient EPO response, impaired iron absorption and release of iron stores from macrophages, increased iron sequestration in bone marrow, spleen and liver; shortened erythrocyte lifespan

Question 55

What does an anemia of inflammatory disease look like?

Answer 55

mild to moderate non regenerative slight microcytosis

Question 56

Name some disorders of nucleic acid synthesis and the anemias they cause.

Answer 56

folic acid deficiency - macrocytic anemia cobalamin deficiency - macrocytic anemia in humans, normocytic anemia in dogs and cats with inherited defects in cobalamin absorption (giant schnauzers, border collies, beagles)

Question 57

Pyridoxine (vitamin b6) deficiency causes what type of anemia?

Answer 57

microcytic anemia (due to disorder in heme synthesis)

Question 58

Lab findings of chronic iron deficiency anemia

Answer 58

* mild to severe anemia * slight to marked microcytosis * normal or decreased MCHC * slight to marked hypochromasia (dogs and ruminants) * low to high retic counts * poikilocytosis in severe animals * thrombocytosis * erythroid hyperplasia in marrow with little or no stainable iron (except this is normal in cats) * low serum iron concentration * normal or high serum TIBC * low saturation of transferrin with iron * decreased serum ferritin

Question 59

Why do erythroid precursors cluster around macrophages in the bone marrow and spleen?

Answer 59

They are obtaining their iron (required for hemoglobin synthesis) from these iron-storing cells as well as from circulating transferrin

Question 60

Name two iron binding/transport proteins

Answer 60

transferrin - beta globulin, correlates with TIBC, transport ferritin - primarily found in cells, few in plasma, correlates with total body iron stores, stain bone marrow with prussian blue to evaluate

Question 61

Compare lab findings in chronic iron deficiency anemia vs. anemia of inflammatory disease.

Answer 61

Question 62

Where does non-regenerative immune-mediated anemia usually occur?

Answer 62

in bone marrow - destruction of RBC precursors, very hard to control

Question 63

What can cause selective erythroid aplasia?

Answer 63

immune mediated - dogs and cats FeLV subgroup C - cats chloramphenicol - cats rhEPO use - dogs, cats, horses congenital - dogs parvovirus vaccine in dogs?

Question 64

Name two groups that suffer from inherited dyserythropoiesis.

Answer 64

polled hereford calves English Spaniel Springer dogs

Question 65

How can you definitively tell an anemia is nonregenerative?

Answer 65

hypoplastic or aplastic bone marrow proliferation or infiltration of abnormal cells into the bone marrow

Question 66

Name some causes of aplastic anemia.

Answer 66

Question 67

Which infectious agents can cause hypoplastic marrow?

Answer 67

chronic Ehrlichia canis infections in dogs FeLV and parvovirus coinfection in cats parvovirus infection in young dogs

Question 68

What are myelophthsises?

Answer 68

* a normocytic-normochromic anemia that occurs when normal marrow space is infiltrated and replaced by nonhematopoietic or abnormal cells. * Causes include tumors, granulomatous disorders, and lipid storage diseases. * Characteristic changes in peripheral blood include anisocytosis, poikilocytosis, and excessive numbers of RBC and WBC precursors.

Question 69

Name some examples of myelophtisis.

Answer 69

myelogenous leukemias lymphoid leukemias myelodysplastic syndromes multiple myeloma myelofibrosis and/or osteosclerosis metastatic neoplasia (primarily lymphomas and mast cell tumors)

Question 70

Relative erythrocytosis occurs due to?

Answer 70

* splenic contraction * excitement * exercise * pain * **dehydration** * water loss * water deprivation * shock with fluid shift into tissues

Question 71

What is absolute erythrocytosis?

Answer 71

primary - normal or low EPO but lots of RBCs, can be due to a condition called polycythemia vera, happens in cattle? secondary - high EPO, hypoxemia (ie. high altitude, heart dz, chronic lung dz, methemoglobinemia) or innapropriate EPO production (renal tumors, renal cysts, hydronephrosis, non-renal EPO secreting tumors)