SA Anemia 1-4 (Wilkinson) Flashcards
Define Anemia
reduction in RBC mass –> reduced O2 delivery to tissue
O2 delivery to tissue depends on what 3 factors
- Blood flow and is distrubution to different organs
- O2 carrying capacity of the blood (Hgb concentration or # RBCs in circulation)
- Oxygen’s ability to extract the RBC into tissues
Body’s physiologic responses (4) to chronic anemia
1. Increases CO
2. Redistributes blood flow to caridac and cerebral circulation (via vasodilation) and decreases to splanchnic vascular bed (GIT, spleen, etc.) & periphery (e.g., pale gums) (via vasocinstriction)
3. Increased erythropoietin production (hormone that signals bone marrow to produce more RBCs)
4. Improved O2 extraction (via compensatory mechanism)
Why do animals with acute onest of anemia tend to have more severe clinical signs/exam changes than those with chronic anemia?
In chronicly anemic animals, the body has gotten used to its anemic state via compensatory mechanisms
3 main causes of anemia
1. Hemorrhage (hypovolemia)
2. Hemolysis (RBC destruction)
3. Hypoplasia (decreased RBC production- bone marrow dz, kidney failure)
Erythropoietin (hormone that stimulates RBC production) is produced in kidneys
First step in assessing anemia is determining whether it’s regenerative or non-regenerative. Define the two and what they each indicate.
Pre-regenerative anemia time period: the time period b/w anemia onset & bone marrow release of reticulocytes
~2-5 days
IMHA or hemorrhage: may initially present as non-regen., but b/c not enough time has lapsed, and not b/c bone marrow isn’t working properly
How to assess RBC regeneration
- Reticulocyte count (expressed as a % of the CURRENT RBC count, so must be corrected for anemia)
- Blood smear (polychromasia and anisocytosis; nRBCs)
- RBC indices (MCV and MCHC)
- Polychromasia and anisocytosis indicate presence of reticulocytes; nRBCs indicate appropriate metarubricytosis if reticulocytosis is present)
- MCV = size of RBCs, MCHC = hemoglobin content of RBCs –> Macrocytosis and hypochromasia (not always abnormal)
Absolute reticulocyte count calculation
ARC = Reticulocyte % x RBC count
Values for regenerative response in dogs vs cats
Dogs: > 95,000/uL reticulocytes
Cats: > 60,000/uL reticulocytes
cats do not have as robust response to anemia as dogs
non-regen = less than these values
What is seen on blood smear of non-regen case
lack of polychromasia and anisocytosis; nRBCs ( = inappropriate metarubricytosis)
Metarubricytosis w/out reticulocytosis is associated with what?
Bone marrow disease or injury, splenic disease, lead poisoning
2 differentials for non-regen anemia:
Either pre-regenerative period or true hypoplasia (in bone marrow)
Hemorrhagic Anemia (Regenerative)
Signs of GIT blood loss
Hemorrhagic Anemia (Regenerative)
Signs of urinary or reproductive tract blood loss
Hematuria (gross or microscopic)
Hemorrhagic Anemia (Regenerative)
Signs of respiratory tract blood loss
- Epistaxis
- Hemopysis (coughing blood)
Hemorrhagic Anemia (Regenerative)
Where are sources of internal blood loss contributing to anemia?
Hemorrhagic Anemia (Regenerative)
3 common causes of acute blood loss
- Trauma
- Coagulopathy
- Neoplasia
Coagulopathy: 1º hemostasis defects (PLTs) or 2º hemostasis defects (clotting factors)
Neoplasia: hemangiosarcoma (liver, spleen, lung)
Hemorrhagic Anemia (Regenerative)
Common causes of chronic blood loss
- GI tract (hookworms, ulcers, neoplasia)
- Fleas
- Urinary tract
- Respiratory tract (chronic epistaxis)
Hemorrhagic Anemia (Regenerative)
Animals with acute hypovolemia usually have what strength of pulses and why?
Weak and thready pulses: they are losing large volumes of blood very quickly
loss of plasma/fluid/plasma proteins
Hemorrhagic Anemia (Regenerative)
Animals with hemolysis-caused anemia typically have what strength of pulse and why?
Hemolysis is NOT a loss of blood volume (pulses can still be strong/bounding)
Hemorrhagic Anemia (Regenerative)
Chronic external hemorrhage vs chronic internal hemorrhage reticulocytes
External chronic: present (regen) or absent (non-regen) –> NON-REGEN b/c they are losing iron in the blood –> microcytic and hypochromic anemia
Internal chronic: present (regen)
Hemorrhagic Anemia (Regenerative)
Relationship b/w iron & RBCs
Iron = essential for hemoglobin production
Hemorrhagic Anemia (Regenerative)
Signs of poor tissue oxygenation (5)
weakness, depression; tachycardia; tachypnea; bounding femoral pulses (or weak w/ acute blood loss)
Indicate start of blood transfusion
PCV < 15%: consider blood transfusion or low PCV + these clinical signs
Hemorrhagic Anemia (Regenerative)
What type of blood product for blood-loss anemia & cogaulopathy?
Fresh whole blood (prior to refrigeration):
- RBC + PLTs + all clotting factors + plasma proteins
- not usually used b/c requires another animal who can immediately donate their blood
Hemorrhagic Anemia (Regenerative)
Refrigerated vs non-refrigerated (stored vs fresh) whole blood products?
- Refrigerated (stored): RBC + some clotting factors (no V or VIII or vWF) + plasma proteins
- Non-refrigerated (fresh): RBC + PLTs + all clotting factors + plasma proteins
vWF clotting factor: attaches to small blood cells called platelets. This helps the platelets stick together, like glue, to form a clot at the site of injury and stop the bleeding.
What type of blood product for hemolytic or hypoplastic anemia?
Packed Red Blood Cells:
- RBC only
Desired PCV after blood transfusion?
~25%
Equation for blood transfusion volume
(BWkg x BVml/kg) x [(PCVdes - PCVpat) / (PCVdon)]
DEA 1.1
Dog Erythrocyte Antigen 1.1
a surface protein on RBC
When will dogs have naturally occurring antibodies against DEA 1.1?
If they are DEA 1.1 (-) and receive a blood transfusion
What blood types are most common in cats?
Types A, B, AB
in U.S.: 99% are type A
Type A cats have _ anti-B antibodies
Type B cats have _ anti-A antibodies
Type A cats have WEAK anti-B antibodies –> these cats will have a negative rxn if given type B blood
Type B cats have VERY STRONG anti-A antibodies –> these cats will DIE if given type blood A
What is a crossmatch
To assess compatibility b/w patient serum (antibody) and donor red blood cells (antigen):
take patient’s serum with donor’s RBCs and see if they react (does pt have antibodies against donor’s antigens)
When should a crossmatch be performed?
- Previous blood transfusion hx or hx is unknown
- If given back-to-back (e.g., IMHA pt in ICU getting q12h) after ≥ 3 days following a known RBC transfusion (time it takes Abs to form)
Blood transfusion rates:
1. first 15 mins
2. second 15 mins (if going well)
3. remainder of 4-hour window
- 1 ml/kg/hr
- 2 ml/kg/hr
- increase to rate that allows for remainder of blood to be administered within the 4-hour window
faster rates can be used if the anemia is life-threatening
TPR q15 mins first hour
TPR q30mins for remaining time
Transfusion Reactions (2) / which is most common and which is life-threatening
- Transfusion-associated circulatory overload (non-immunologic) = pt gets fluid-overloaded
- Non-hemolytic febrile reaction (immunologic) = immune response to the transfused blood, very common but not life-threatening.
- Hemolytic transfusion reaction (immunologic) = anaphylaxic reaction which can lead to shock: febrile + tachypnea + tachycardia + vomiting + hypotension
Hemolytic transfusion reaction
IV hemolysis which is completely destroying the transfused blood –> stop immediately and treat supportively (IVF, O2, corticosteroids, vasopressors). Can check PCV to see if blood is hemolyzed.
Hemolytic Anemia (Regenerative)
EV vs IV hemolysis (mechanism + color of blood/urine)
CS: icterus, splenomegaly (EV), fever (IMHA, infectious anemia), bounding femoral pulses)
Hemolytic Anemia (Regenerative)
Blood smear findings for EV vs IV hemolysis
EV: spherocytes
IV: ghost cells
Hemolytic Anemia (Regenerative)
Differentials for EV hemolysis
1. IMHA (1º = idiopathic//most common; 2º = infection, neoplasia, drugs or vaccines)
2. Oxidant injury
3. Infectious Anemia
4. Abnormal mø activation and/or proliferation (UNCOMMON, but due to erythophagocytic histiocytic sarcoma or hemophagocytic syndrome)
EHS: møs have malignant characteristics, versus HS = too many møs present
Hemolytic Anemia (Regenerative)
What drug classes (3) can secondarily cause IMHA?
Sulfonamides, penicillins, cephalosporins
Hemolytic Anemia (Regenerative)
Most common infectious causes of IMHA in dogs (1) versus cats (3)
Dogs: Babesia spp.
Cats: Mycoplasma haemofelis, FeLV, FIP
Hemolytic Anemia (Regenerative)
Autoagglutination, Spherocytosis, and positive Coombs test are strong evidence of what?
IMHA
- BOTH dogs & cats will have autogluttination
- ~75% of IMHA DOGS will have spherocytes on path review
- Consider Coombs if ^^ are unidentified
Hemolytic Anemia (Regenerative)
First line of treatment for IMHA
Corticosteroids
- Prednisone/prednisolone (rapid onset of 5-7 days for full effect)
Hemolytic Anemia (Regenerative)
3 side effects of corticosteroids that are dose-dependent.
Iatrogenic hyperadrenocorticism –> adrenal gland suppression
- PU/PD, polyphagia, weight gain, panting, haircoat changes
Cats: insulin resistance –> 2º diabetes millitus
Mild-moderate elevated ALKP and GGT
Hemolytic Anemia (Regenerative)
Azathioprine side effects (3)
an immunosuppr. that can be used in combo w/ corticosteroid
Bone marrow suppression
- monitor serial CBCs
Hepatotoxicity
- monitor liver enzymes
Pancreatitis
Hemolytic Anemia (Regenerative)
Mycophenolate side effects (2)
an immunosuppr. that can be used in combo w/ corticosteroid
Potentially severe GI upset
- may be delaye dup to weeks after starting medication
Bone marrow suppression
- less likely than Azothioprine
Hemolytic Anemia (Regenerative)
Cyclosporine side effects (3)
an immunosuppr. that can be used in combo w/ corticosteroid
- GI upset
- Gingival hyperplasia
- Increased risk for opportunistic fungal infections
Hemolytic Anemia (Regenerative)
Complications associated with IMHA?
- Systemic thromboembolism
- Acute kidney injury (AKI)
- Disseminated intravascular coagulation (DIC)
- Opportunistic infections (integument, UT, RT; bacterial andor fungal pathogens
Low-dose Aspirin (0.5-1.0 mg/kg SID) or Clopidogrel (1-4 mg/kg SID) should be started right when you diagnose IMHA as a preventative measure
Hemolytic Anemia (Regenerative)
Infectious Anemia: pathogenesis and potential 2º IMHA
Agents directly damage RBCs –> causes hemolysis. Can activate the immune system into thinking hte RBCs are pathogens and can trigger 2º IMHA (from induced Ab formation against RBCs
Hemolytic Anemia (Regenerative)
Hemotropic Mycoplasma and effects
Mycoplasma haemofelis = important organism that causes severe hemolytic anemia in cats
- Epicellular parasite of RBCs –> direct damage + triggers erythrophagocytosis (EV hemolysis)
Hemolytic Anemia (Regenerative)
Risk factors for hemotropic myoplasma in cats
- male
- outdoor access (other cats, flea/arthropods)
- FeLV or VIF (+)
Hemolytic Anemia (Regenerative)
Babesiosis
Babesia canis vogeli
- pathogenesis
- transmission
- large, piriform-shaped protozoan exisiting within erythrocytes (singly or paired) that causes 2º IMHA
- brown dog tick (Rhipicephalus sanguineus)
- subclinically infected animals can be carriers (e.g., greyhounds)
greyhouds almost always subclinically infected –> if greyhound dx with IMHA, always look for B. canis as well
Hemolytic Anemia (Regenerative)
Babesiosis
Babesia gibsoni
- pathogenesis
- transmission
- Small protozoan existing within erythrocytes with ring-like configuration
- Bite wounds likely play a role in transmission
- Sub-clinically infected dogs can be carriers (e.g., American pitt bulls)
Hemolytic Anemia (Regenerative)
How is Babesiosis best diagnosed?
PCR (is species-specific/most sensitive)
Hemolytic Anemia (Regenerative)
Cytauxzoonosis
Cytauxzoon felis
- transmisison
- two forms
- Tick-transmitted protozoan infection of cats (Lone Star = Amblyomma americanum)
- Forms:
1. Tissue phase (schizont) - infects mononuclear phagocytes
2. Erythrocyte phase (piroplasm)
Dx = blood smear or PCR
Hemolytic Anemia (Regenerative)
Oxidant-Induced Hemolytic Anemia
- etiology
- Hbg is constantly being oxidized, and is reversed by a reducing mechanism.
- Certain toxins can cause massive/rapid oxidation –> reducing mechanism becomes overwhelmed –> Hgb damage (Heinz body formation or methemoglobinemia)
Hemolytic Anemia (Regenerative)
Heinz bodies
denatured, oxidized hemoglobin –> hemolysis
Hemolytic Anemia (Regenerative)
Culprits of Heinz Body Oxidant-Induced Hemolytic Anemia
Hemolytic Anemia (Regenerative)
What toxicity that causes Heinz Body Oxidant-Induced Hemolytic Anemia can mimic IMHA? How is it diagnosed?
Zinc toxicity (pennies minted post 1982). Dx via abd rads!
All pts with hemolysis shoild have abd rads performed (FB)
Hemolytic Anemia (Regenerative)
Methemoglobinemia
- etiology
- causes
- Methemoglobin = oxidized heme iron
- Is a “physiologic anemia” = normal RBC but has reduced O2 carrying capacity
- Causes = Acetominophen
Hemolytic Anemia (Regenerative)
Tx for Oxidant-Induced Hemolytic Anemia (3)
- Remove offending drug or toxin
- N-acetylcysteine (antioxidant that helps increse the reducing mechanism = increase intracellular gluthaione levels)
- Supportive care (Heinz body anemia = blood transfusion if indicated; Methemoglobinemia = supplemental O2)
Hemolytic Anemia (Regenerative)
Fragmentation Hemolytic Anemia (also known as microangiopathic hemolytic anemia)
- etiology
- causes
- RBC fragmentation due to contact w/ abnormal vasculature
- HW disease, DIC, splenic torsion, hemangiosarcoma, vasculitis
Is NOT an immune response against RBCs
Hemolytic Anemia (Regenerative)
Blood smear findings of fragmentation hemolytic anemia
- Schistocytes
- Acanthocytes
Hypoplasia Anemia (Non-Regenerative)
Primary Hypoplasia Anemia
- definition
- causes (3)
Decreased production INSIDE the bone marrow
- 1º failure of erythropoiesis (RBC only)
- Aplastic anemia/pancytopenia (multiple cell lines –> e.g., PLTs or WBCs affected plus the RBCs)
- Infiltration of bone marrow w/ disease, directly affecting erythropoiesis
Hypoplasia Anemia (Non-Regenerative)
Secondary Hypoplasia Anemia
- definition
- causes (2)
Disease is OUTSIDE of the bone marrow
- Hgb synthesis defect = iron deficiency (RBC only)
- 2º failure of erythropoiesis (RBC only)
1º Hypoplasia Anemia (Non-Regenerative)
Primary failure of erythropoiesis pathogenesis
IMHA, but at the bone marrow level
- The precursor RBCs in the bone marrow are getting attacked
- severe anemia often present (is a chronic condition)
- other cell lines are normal (leukocytes, platelets)
- is a.k.a. pure red cell aplasia and non-regen. immune-mediated anemia
1º Hypoplasia Anemia (Non-Regenerative)
Key difference b/w Pure Red Cell Aplasia and Non-Regenerative Immune-Mediated Anemia and traditional IMHA?
Pure Red Cell Aplasia and Non-Regenerative Immune-Mediated Anemia have much slower remission times than IMHA (as long as 3-4 months)
1º Hypoplasia Anemia (Non-Regenerative)
Aplastic Anemia (Pancytopenia)
Peripheral blood cytopenias due to hypocellular/acellular bone marrow
1º Hypoplasia Anemia (Non-Regenerative)
Bone Marrow Infiltration (Myelophthisis)
Dispalcement of bone marrow tissue by…
- neoplastic cells
- collagen (myelofibrosis) –> idiopathic, potentiallly immune-mediated; dr
- adipose tissue
2º Hypoplasia Anemia (Non-Regenerative)
Hemoglobin synthesis defect’s CBC progression in iron deficiency
2º Hypoplasia Anemia (Non-Regenerative)
What is the most common cause of non-regenerative anemia in dogs and cats? How severe is the anemia typically? Characteristics of the RBCs?
Anemia of chronic disease // of inflammatory disease
- mild-moderate anemia (Dogs: PCV = 20-37%, Cats: 15-26%)
- Always normocytic and normochromic anemia, all other cell lines normal
anemia resolves once underlying disease (underlying inflamm. disease) is addressed
2º Hypoplasia Anemia (Non-Regenerative)
How does Chronic Kidney Disease lead to 2º hypoplastic anemia?
- lack of erythropoietin production; GI blood loss, decreased RBC life span
2º Hypoplasia Anemia (Non-Regenerative)
When would you expect total solids to be low?
Hemorrhage
2º Hypoplasia Anemia (Non-Regenerative)
When would you expect plasma color to appear yellow or red/pink?
Hemolysis
2º Hypoplasia Anemia (Non-Regenerative)
When would you expect to see Spherocytes, +/- ghost cells, on blood smear?
Hemolysis
When would you not expect to see agglutination on blood smear?
Hemorrhage and hypoplasia; may or may not with hemolysis
