Approach to Anemia in Small Animals Flashcards
what is anemia
reduction in hemoglobin concentration of the blood
how are red blood cells produced
- stem cells are hematopoietic
- progenitor cell line: precursor cells to RBCs —> rapidly dividing in the bone marrow
- precursor cells: reticulocytes
- mature red blood cells
Slow progression and then exponential division
what cells support the production of red cells
Under the influence of EPO from the kidneys under the influence of renal hypoxia
Stromal cells in the bone marrow produce cytokines which support this process
Iron: stored as hemosiderin in macrophages
describe the breakdowns of the different anemias
non-regenerative
“pre-regenerative”
regenerative (hemorrhage, hemolysis)
what are the causes of non-regenerative anemias (7)
- primary bone marrow disease
- iron deficiency anemia
- anemia of inflammatory disease
- chronic renal failure
- endocrine renal failure
- endocrine disease (hypothyroidism)
- cobalamin deficiency
what are the causes of regenerative hemolytic anemias (4)
- IMHA
- infectious
- oxidative injury
- metabolic disorders
what are the causes of regenerative hemorrhagic anemias (4)
- trauma
- GI ulceration
- hemostatic disorder
- ruptured neoplasm
what are primary bone marrow disease (5)
- pure red cell aplasia
- aplastic anemia
- myelofibrosis
- bone marrow infiltration
- myelodysplastic syndromes
what are the causes of secondary failure of erythropoiesis (5)
- anemia of inflammatory disease
- chronic renal failure
- endocrine disease
- hemoglobin synthesis defects: Fe deficiency
- nuclear maturation defects: cobalamin deficiency
what is pure red cell aplasia
anemia affecting the precursors to red blood cells but not to white blood cells
what is aplastic anemia
a bone marrow failure where all cell lines are reduced (infectious disorders such as FeLV or some toxicities)
what is myelofibrosis
bone marrow failure secondary to replacement of normal marrow elements with fibrous tissue —> crowds it so there’s less space for hematopoiesis to occur
what is bone marrow infiltration
crowding of bone marrow and can cause other cell lines to become affected (lymphomas, etc.)
what is myelodysplastic syndromes
ineffective hematopoiesis —> non-regenerative anemia or other cytopenias (most common in cats)
what is anemia of inflammatory disease
inflammatory process that is influencing the bone marrow’s ability to utilize iron. The iron becomes sequestered —> anemias are mild to moderate and are rarely the reason for the animal’s presenting signs
how does chronic renal failure cause secondary failure of erythropoiesis
ate stage renal failure —> failure of production of EPO
what endocrine diseases can cause secondary failure of erythropoiesis
hypothryoidism
what are the distinguishing clinical features of non-regenerative anemia due to primary bone marrow disease (3)
- clinical signs related to gradual reduction in oxygen carrying capacity –> lethargy/weakness/exercise intolerance
- relatively BAR for degree of anemia
- other cell lines may be affected: thrombocytopenia/neutropenia
what are the distinguishing features of non regenerative anemia due to secondary failure of erythropoiesis
clinical signs relate to primary disease process
what are the distinguishing features of non regenerative anemia due to secondary failure of erythropoiesis in chronic renal failure
PUPD, reduced appetite, weight loss, vomiting
what are the distinguishing features of non regenerative anemia due to secondary failure of erythropoiesis in hypothyroidism
dermatological disease (bilateral symmetrical alopecia)
what are the distinguishing features of non regenerative anemia due to secondary failure of erythropoiesis in Fe deficiency
typically associated with chronic low grade external blood loss due to parasitism (internal or external), ulcerative GI disease, chronic urinary loss (often owners don’t notice the chronic blood loss and patients often present because of severe anemia)
what are the distinguishing features of non regenerative anemia due to secondary failure of erythropoiesis in cobalamin deficiency
typically associated with chronic GI disease, or rarely with genetic defects resulting in inability to absorb vitamin B12
what are the two categories of hemolytic anemia
- immune mediated
- non immune mediated
what are the immune mediated causes of hemolyitc anemia
primary (auto immune) IMHA
secondary IMHA
what are the non immune mediated causes of hemolytic anemia (6)
- oxidative injury
- heinz body anemia
- erythrocyte enzymopathies
- increased erythrocyte fragility
- microangiopathic anemia
- hemophagocytic syndrome
what is immune mediated hemolytic anemia caused by
Anemia characterized by the presence of erythrocyte-bound antibody and/or complement
what are the two methods of hemolysis in immune mediated anemia (2)
1. extra-vascular hemolysis: antibody with RBC becomes opsonized and macrophages phagocytize them —> occurs within the liver and spleen. The macrophages are removing these RBC from the circulation and destroying them
2. intravascular hemolysis: once antibodies are bound to RBC —> compliment fixation and causes a membrane attack on the RBC
what are the causes of secondary IMHA (3)
- Infectious: bacterial (leptospirosis, hemoplasmas) or parasitic (babesia, leishmania, ehrlichia)
- Drug-induced: sulphonamides, penicillins, vaccines
- Neoplasia: lymphoma, leukemias, multiple myeloma
what does feline infectious anemia cause
causes hemolysis involving immune mediated and direct erythrocyte damage (plus sequestration)
what is the most common reason for hemolytic anemia in cats
feline infectious anemia
what pathogens cause feline infectious anemia
Mycoplasma hemofelis
M. hemominutum (FeLV)
M. turicensis
what type of anemia does feline infectious anemia cause
Typically regenerative (although concurrent disease may result in non-regenerative anemia)
what is seen on blood smears in feline infectious anemia
Hemoplasmas seen on blood smears
Ddx Howell-Jolly bodies (little blue dots)
how is feline infectious anemia diagnosed
PCR
coombs positive (but not always)
what does canine babesiosis cause
hemolytic anemia including IMHA
what are the clinical signs of canine babesiosis (4)
- pyrexia
- thrombocytopenia
- +/- splenomegaly, hyperbilirubinemia, hemoglobinuria
- +/- AKI, hepatopathy, SIRS, CNS dysfunction
what are causes of oxidative injury/heinz body anemia (6)
- Paracetamol toxicity
- Onion toxicity
- Benzocaine
- Zinc toxicity
- Propofol infusion
- Diabetes mellitus, hepatic lipidosis in cats
what are additional clinical signs you might see associated with hemolytic anemia (5)
- jaundice
- hemoglobinuria (intra vascular)
- hepato-splenomegaly
- pyrexia
- chocolate coloured oral mm as a sign of metHb
what are examples of regenerative hemorrhagic anemias
- trauma
- GI ulceration
- hemostatic disorders
- ruptured neoplasm
what are evidence of hemorrhage/blood loss anemias (3)
- evidence of bleeding: external or internal
- signs of hypovolemia
- evidence of hemostatic disorder: petechiation/ecchymoses
what are signs of external hemorrhage/bleeding
- melena
- hematuria
what are the signs of internal bleeding/hemorrhage
- free abdominal fluid/abdominal distention
- signs of intrathoracic hemorrhage (restricted breathing pattern with a pleural effusion)
what are laboratory evaluations that can assist in anemia diagnostics (6)
- PCV
- blood smear
- reticulocyte assessment
- complete blood count
- serum biochemistry
- ISA, coagulation times, etc
what is the approach to the anemia patient
what questions can the laboratory evaluation explain (6)
- how severe is the anemia? does it explain the clinical presentation?
- is the anemia regenerative or non-regenerative? is the anemia appropriately regenerative?
- what do the RBCs look like on blood smear? evidence of IMHA? evidence of oxidative injury? iron deficiency?
- could the anemia be secondary to a bleeding disorder? does the patient have enough platelets? evidence of coagulopathy?
- are other cell lines affected? could the anemia be due to bone marrow failure?
- is there biochemical evidence of an underlying disease?
what provides information on how severe the anemia may be
PCV
clinical status
what PCV % is mild anemia
30-39%
what PCV % is moderate anemia
20-30%
what PCV % is severe anemia
<20%
what are signs of regenerative anemia on blood smear
- anisocytosis
- polychromasia
- nucleated RBCs
- reticulocytes
how is the adequacy of regenerative response assessed (3)
- absolute reticulocyte count (normal < 60 x 10^9/l in dogs)
- corrected reticulocyte count (normal <1%)
- reticulocyte production index
how do you determine if anemia is non-regenerative with the reticulocyte response
if <50% of expected response
the expected response is dependent on the severity of the anemia
pre-regenerative anemia may appear non-regenerative if inadequate time for regenerative response to occur
what are spherocytes
sphere shaped red blood cells
indicative of hemolytic anemia
what is the mean cell volume
how large the red cells are
macrocytic
normocytic
microcytic
what is the mean corpuscular hemoglobin concnetration
levels of Hb in red cell
normochromic
hypochromic
what type of laboratory features does primary bone marrow disease show
typically normocytic normochromic anemia
concurrent bi-cytopenia or pan-cytopenia
what lab features does Fe deficiency anemia show
microcytic hypochromic anemia
what lab features does chronic renal failure anemia show
biochemical evidence of renal failure –> azotemia
what lab features does inflammatory anemia show
rarely the most significant clinical abnormality –> typically mild to moderate anemia
what are the distinguishing lab features of IMHA (6)
- regenerative anemia
- spherocytes
- leukocytosis due to a neutrophilia +/- left shift
- Evan’s syndrome: concurrent immune mediated thrombocytopenia
- hyperbilirubinemia
- evidence of organ dysfunction: increased ALT, increased canine pancreatic lipase immunoreactivity
what are confirmatory tests for IMHA
- positive slide agglutination test
- positive coombs’ test
what are distinguishing lab features of hemorrhage/blood loss anemia (4)
- regenerative anemia (may be “pre-regenerative” though)
- concurrent hypoproteinemia
- presence of RBC fragmentation/schistocytes on blood smear
- lab evidence of hemostatic disorder: thrombocytopenia, prolongation of coagulation times
if a dog has severe (PCV <20%), microcytic, hypochromic anemia which is poorly regenerative what is the likely cause
iron deficeincy anemia
if a dog has moderate to severe, regenerative anemia with spherocytosis what is the likely cause
IMHA
how is IMHA diagnosed
- presence of marked spherocytosis on blood smear
- positive in saline slide agglutination test
- positive coombs test
what are further investigations if you suspect IMHA
identify and address underlying cause
- thoracic and abdominal imaging
- urinalysis including C&S
- infectious disease testing?
how is IMHA managed
- immunosuppressive drug therapy
- supportive care (transfusion?)
- prevention/management of complications
what immunosuppressive drugs are used to treat IMHA
first line: prednisolone, dexamethasone
second line: azathioprine, ciclosporin, mycophenolate mofetil (MMF), human intravenous immunoglobin
what do first line immunosuppressive drugs do
block the ability of macrophages to remove antibody coated RBCs from circulation
with prolonged therapy they reduce antibody production
what do secondary line immunosuppressive drugs do
block the production of antibodies
what is the prognosis of IMHA
25-70% mortality
what is the cause of death in IMHA (4)
- refractory to trauma
- hypoxemia
- pulmonary thromboembolism
- disseminated intravascular coagulation
how is thromboembolic disease prevented
thromboprophylaxis: aspirin or clopidogrel
how is pulmonary thromboembolism disease managed
oxygen
heparin in addition to clopidogrel
