Evaluation of Erythrocytes: Anemia and Regeneration Flashcards
What important information from a history can help you diagnose the cause of an anemia?
prior drug administration exposure to toxic chemicals or plants family or herd occurrence recent transfusion or colostrum ingestion age at onset of anemia
Physical findings associated with anemia
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
Normal HCT with low TPP leads you to what DDX?
GI protein loss proteinuria liver dz
Normal HCT with high TPP leads you to what DDX?
increased globulin synthesis dehydration masked anemia
High HCT with low TPP leads you to what conclusion?
protein loss combined with relative or absolute erythrocytosis
High HCT + High TPP = ?
dehydration
Low HCT + low TPP =?
substantial ongoing or recent blood loss, overhydration
High HCT + normal TPP =
splenic contraction absolute erythrocytosis dehydration masked hypoproteinemia
low HCT + normal TPP =
increased erythrocyte destruction, decreased erythrocyte production, chronic hemorrhage
low HCT + high TPP =
anemia of inflammatory dz multiple myeloma lymphoproliferative dz
How do you classify an anemia as regenerative or non regenerative?
absolute reticulocyte count increased increased polychromasia on blood film marrow evaluation
What are the size and color classifications of anemia?
microcytic (MCV below reference), normocytic (MCV in reference), macrocytic (MCV above reference) hypochromic (MCHC below reference), normochromic (NO hyperchromic)
T/F hemodilution is a true anemia
F
T/F severity can rule in or out a specific cause of anemia
T - ie. severe anemia should not be attributed alone to anemia of inflammatory disease
What are the four pathophysiologic mechanisms of anemia?
blood loss or hemorrhage accelerated erythrocyte destruction (hemolysis) reduced/defective erythropoiesis hemodilution (not really an anemia)
Hemodilution “anemia”
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
Which species is not ideal for a bone marrow evaluation?
Horses
What does regenerative anemia look like on blood films?
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
Why would an acute hemorrhagic or hemolytic anemia initially appear non-regenerative?
because it takes bone marrow 3-5 days to respond to an anemia
What are features that may be seen in blood smears as part of the regenerative response but are not specific for regeneration?
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)
How does MCV change in a regenerative response to anemia?
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
What does the MCHC look like in a regenerative anemia?
within reference range early low with a high percentage of reticulocytes, especially “stress reticulocytes”=released early from BM
Clinical signs of hemolytic anemia
depends on severity and speed of onset icterus may be present if rapid RBC destruction red plasma hemoglobinuria (if intravascular hemolysis present)
Laboratory findings of hemolytic anemia
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)
Extravascular hemolysis often occurs in which organs?
spleen, liver, bone marrow
Which is acute or chronic - extravascular hemolysis or intravascular hemolysis?
Extravascular - can be either
intravascular - often rapid - per acute or acute
DIC occurs as a result of ________ (extravascular/intravascular) hemolysis.
both can cause DIC
Which has a worse prognosis intravascular or extravascular hemolysis?
intravascular - abnormal location for RBC destruction, usually rapid, not an isolated environment = fragments are a risk for DIC and anaphylactic shock
What is the pathological mechanism that causes hemoglobinuria?
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
Where does bilirubin back up to first (if RBC destruction too rapid/severe to be excreted via normal mechanisms)?
backs up to urine and feces first = bilirubinuria then backs up in plasma = bilirubinemia then backs up to mucocutaneous tissues = icterus
Which of the following conditions distinguish intravascular from extravascular hemolysis? bilirubinuria bilirubinemia hemoglobinuria hemoglobinemia
hemoglobinemia hemoglobinuria
Name some causes of hemolytic anemias.
- immune-mediated
- hemoparasites
- infectious agents
- chemicals and plants
- fragmentation
- hypoosmolality
- hypophosphatemia
- hereditary RBC defects
What are some of the causes of immune-mediated erythrocyte destruction?
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)
Describe the pathological mechanism of IMHA.
attachment of IgG or IgM causes fixation of complement to RBC membranes - Macrophages phagocytize them - forms spherocytes
How can you detect IMHA in a dog?
Coombs test - but be careful because false positives and negatives do occur
Name three erythrocyte parasites.
anaplasma (ruminants) mycoplasma (not in horses) babesia cytauxzoon felis (non regenerative) theileria (ruminants and horses)
Name some infectious agents that cause IMHA.
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)
Name two chemicals/plants that can cause anemia.
Name two causes of hypoosmolality.
hypotonic fluid administration - IV or oral
water intoxication
Name two causes of hypophosphatemia.
decreased RBC ATP concentration
postparturient hemoglobinuria
ketoacidotic diabetes mellitus following insulin therapy (cats and dogs)
hepatic lipidosis (cats)
hyperalimentation (dogs and cats)
Miscellaneous hemolytic anemias
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
Causes of blood loss anemia
trauma
blood sucking parasites
coagulation disorders
neoplasia
GI ulcers
inflammatory bowel diseases
Distinguish between external and internal hemorrhage
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
Causes of acute hemorrhage
trauma
recent surgery
bleeding ulcers
bleeding tumors (esp. hemangiosarcoma)
severely marked decrease in platelets (thrombocytopenia usually less than 25k/microliter)
inherited or acquired coagulopathies
Acute hemorrhage laboratory findings
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
How can a chronic blood loss cause a non-regenerative anemia?
if severe iron deficiency develops
Lab findings of chronic blood loss
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
Describe the mechanism of the development of iron deficiency anemia.
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
Causes of iron deficiency anemia
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
Name causes of a macrocytic anemia.
FeLV infection in cats
myeloproliferative disorders
folate deficiency
dyserythropoiesis
What are some causes of non-regenerative anemias?
- 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
What are the causes of anemia from chronic renal dz?
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
Non regenerative anemias due to endocrine disorders produce what type of anemia?
moderate normocytic normochromic
not associated with poikilocytosis
Describe the pathogenesis of anemia of chronic inflammatory dz.
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
What does an anemia of inflammatory disease look like?
mild to moderate non regenerative
slight microcytosis
Name some disorders of nucleic acid synthesis and the anemias they cause.
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)
Pyridoxine (vitamin b6) deficiency causes what type of anemia?
microcytic anemia (due to disorder in heme synthesis)
Lab findings of chronic iron deficiency anemia
- 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
Why do erythroid precursors cluster around macrophages in the bone marrow and spleen?
They are obtaining their iron (required for hemoglobin synthesis) from these iron-storing cells as well as from circulating transferrin
Name two iron binding/transport proteins
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
Compare lab findings in chronic iron deficiency anemia vs. anemia of inflammatory disease.
Where does non-regenerative immune-mediated anemia usually occur?
in bone marrow - destruction of RBC precursors, very hard to control
What can cause selective erythroid aplasia?
immune mediated - dogs and cats
FeLV subgroup C - cats
chloramphenicol - cats
rhEPO use - dogs, cats, horses
congenital - dogs
parvovirus vaccine in dogs?
Name two groups that suffer from inherited dyserythropoiesis.
polled hereford calves
English Spaniel Springer dogs
How can you definitively tell an anemia is nonregenerative?
hypoplastic or aplastic bone marrow
proliferation or infiltration of abnormal cells into the bone marrow
Name some causes of aplastic anemia.
Which infectious agents can cause hypoplastic marrow?
chronic Ehrlichia canis infections in dogs
FeLV and parvovirus coinfection in cats
parvovirus infection in young dogs
What are myelophthsises?
- 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.
Name some examples of myelophtisis.
myelogenous leukemias
lymphoid leukemias
myelodysplastic syndromes
multiple myeloma
myelofibrosis and/or osteosclerosis
metastatic neoplasia (primarily lymphomas and mast cell tumors)
Relative erythrocytosis occurs due to?
- splenic contraction
- excitement
- exercise
- pain
-
dehydration
- water loss
- water deprivation
- shock with fluid shift into tissues
What is absolute erythrocytosis?
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)
