Hematology: Erythrocyte Abnormalities Flashcards Preview

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Flashcards in Hematology: Erythrocyte Abnormalities Deck (45):

Effects of radiation on bone marrow

Which cells affected first?

Leukopenia-->especially neutrophils- why? shortest lifespan

Bone marrow gets damaged-->DNA damage, ROS--> unable to replace n'phils--> susceptible to infection

platelets affected next, can't clot--> bleeding

Eventual anemia, intestinal tract, and skin epithelia destroyed.



a reduction in erythrocyte number and or the hemoglobin concentration i.e. decreased RBC, HCT/PCV and or Hb

Not a final diagnosis- must look for underlying cause

Anemia isn't a disease, it's a clinical finding. 


Clinical features of acute anemia



muscular weakness

subnormal temperature




Clinical features of chronic anemia


exercise intolerance




cardiac (haemic) murmur- develop murmur d/t change in blood viscosity (decrease in rbcs, decrease in viscosity, more turbulence) 


Causes of anemia

1) decreased number of erythrocytes entering the blood i.e. decreased production/bone marrow issue


2) increased number of erythrocytes exiting the blood 

decreased O2-->kidneys detect hypoxia-->increased EPO-->bone marrow increases RBC production.

If BM is functioning normally, increased numbers of reticulocytes appear in blood=regeneration (replacing damaged or lost rbcs)

NB: it takes 3-5 days for this to occur 


Types of anemia

Non-regenerative: decreased production

can be due to primary BM disorder, or secondary BM disorder (i.e. renal failure, not enough EPO, not stimulating BM)

Regenerative: increased exit or turnover of RBCs

can be due to: 1) hemolysis (increased destruction of RBCS) a) intravascular or b) extravascular 

or 2) hemorrhage a) internal or b) external 


How do we tell if anemia is regenerative?

** increased number of reticulocytes in blood (nb not in horses)

Macrocytic hypochromic: increased MCV (because reticulocytes are larger), decreased MCHC because reticulcytes are bigger, Hb concentration is decreased, but not the AMOUNT of Hb. 

increased polychromasia (abnormally high number of RBCs in blood) /increased anisocytosis (RBCs are of unequal size)

Sometimes see normoblasts

Basophilic stippling (cattle): tend to see blue/black dots on RBCs.


Hemorrhagic anemia

blood loss

Acute: after accidents or sx

Chronic: bleeding from ulcers, neoplasms or parasites

Coagulopathies: e.g. rodenticide

Internal: animal isn't losing all red cells to outside world, macrophages can mop up and save iron.

external: less iron, less red-cells--> may have impact on BMs ability to make new RBCs. 


Blood findings in hemorrhagic anemia

Normal in first few days--> pre-regenerative

Regenerative: polychromasia (increased number of RBCs in blood due to presence of reticulocytes)

Anisocytosis: difference in red blood cell size (reticulocytes bigger than rbcs)

Howell Jolly body: nuclear remnants in circulating erythrocytes (nb: presence usually signifies damaged spleen)

Thrombocytosis: increase in number of platelets in circulation--> reactive response

Neutrophilia: due to stimulation, stress and inflammation

All of these result in macrocytic hypochromic--> i.e. increased  mean cell volume. 


Degree of regeneration in hemorrhagic anemia factors

Degree of regeneration depends on:

severity of blood loss

location of bleeding: internal vs. external-- in internal bleeding, iron is available for Hb synthesis= greater regeneration

Proteins: not just red cells being lost--> hypoproteinemia (classicaly a panhypoproteinemia). 


Hemolytic anemia

two important features:

1)reduced red blood cell survival time

2) iron from destroyed erythrocytes is retained in the body

Blood picture: markedly regenerative and additional finidings depend on pathogenesis. 


Methods of red cell destruction in hemolytic anemia

1) extravascular lysis (phagocytosis)- mostly in spleen

2)intravascular lysis- RBCs being destroyed in the bloodstream. 


Extravascular lysis of RBCs

Phagocytosis of red cells--> spleenic englargement

Iron and globin is reused

Haem--> biliverdin-->bilirubin (not h2o soluble)

Bilirubin transported by albumin (jaundice)

In liver, bilirubin and glucuronide are conjugated (h2o soluble)--> bile

nb: herbivores may have yellowish plasma anyway (don't confuse with jaundice). 

Look for icterus in mucosal membranes, sclera. where there's more elastic fibers, that's where you see jaundice. 


Intravascular lysis

Lysis of RBCs in the circulation-->free Hb in the blood--> hemoglobinemia

Free Hb-->+haptoglobins-->phagocytosis-->jaundice (if amount exceeds phagocytic capability)

Saturation of haptoglobins-->Hb appears in kidneys-->Hemoglobinuria-->toxic nephrosis

Hematuria: post centrifugation- red cells sediment at bottom

Hemoglobinuria: post centrifugation, whole sample stays red. 


Causes of hemolytic anemia

Inherited: phosphofructokinase deficiency of springer spaniels; pyruvate kinase deficiency of basenjis; NB inherited hemolytic anemia is REALLY rare.

Acquired: much more common- Infectious agents, oxidative compounds and toxins, fragmentation (increased mechanical trauma), immune-mediated. 


Infectious hemolytic anemia

mycoplasma spp, babesiosis

blood picture of mycoplasma hemofelis infxn: small reddish magenta dots in blood cells. macs try to remove these cells. can trigger immune-mediated destruction as well. 

blood picture of babesia divergens in cattle: pear-shaped bilobed organism in red cells; causes intravascular lysis--> hemoglobinuria. 


Toxic and oxidative hemolytic anemia

Oxidative agents in drugs can reduce glutathione levels on RBCs

Haem iron can be oxidized to methaemoglobin (chocolately brown color to blood)

Oxidative damage to hemoglobin causes Heinz body formation--> destoryed by intra- or extravascular lysis. 

heinz body: inclusions within rbcs composed of denatured hemoglobin. 


Heinz bodies

inclusions on RBCs of denatured hb

nb: completely healthy and normal cats have heinz bodies

see heinz bodies in GI disease, diabetes, hyperthyroidism in cats

rarely seen in dogs except in onion/garlic poisoning. 

easier to see on new methylene blue stain. 


Causes of toxic/oxidative hemolytic anemia

cooper poisoning (ruminants)

paracetamol (cats especially)



brassicas (rape and kale)

red maple (horses)

snake venoms 


Fragmentation hemolytic anemia

RBCs subjected to excessive trauma

features of intravascular lysis may be present

Schistocytes ( shredded red cells) and acanthocytes (intact red cells, but irregularly shaped (spiculated)

small vessel disorders: microangiopathic

large vessel disorders 

valve lesion: stops heart valve from closing--> increased turbulence-->red cells bash against each other--> mechanical trauma

metastatic cancer (lungs): tumours disrupt capillary network--> increased mech. trauma to red cells.

thrombus in blood vessel: impeded blood flow in that blood vessel--> mechanical trauma of red cells trying to squeeze past thrombus.  


Immune-mediated hemolytic disorders

Blood group incompatabilities: blood transfusion reaction (naturally occuring ABs to other blood groups); neonatal isoerthyrolysis

Immune-mediated hemolytic anemia generated against self-antigen/own red cells



hemolytic disease of the newborn

Maternal blood group ABs are absorbed from colostrum, destroying neonate's RBCs.

This occurs when mother's blood group is different to the new born's AND the mother has been previously sensitised to that blood grup (i.e. she's developed ABs to foal's red cell type, either from previous pregnancy, or vax, or blood products). 

Dam with sensitization to foreign antigens-->formation of alloantibodies-->neonate ingests colstrum and absorbs antibodies which are dictate against own blood type--> destruction of RBCs-->occur via phagocytosis or intravascular lysis. 


How to avoid isoerythrolysis

indirect coomb's test if mare has ABs against stallions RBCs. if sensitized, attach another AB to cause agglutination. if she does have ABs, can stop foal getting colostrum from mom. 

signs develop 12-48 hours after birth. 


IMHA in adults

primary/autoimmune (idiopathic)

secondary: under-lying trigger; i.e. drugs/toxins, infectious agents, neoplasia, vaccines?

Dogs often primary/idiopathic

other species uncommon and usually secondary. 


Canine IMHA (auto-immune)

production of autoantibodies against own rbc

IgM or IgG

autoantibodies may be agglutinins (clumping) or lysins or incomplete (incomplete triggering of complement cascade)

Warm or cold reacting. 


Warm antibody AIHA

reacting at body temp

incomplete IgG coats RBC

completely/partially phagocytosed in spleen (incomplete activation of complement cascade)

-spherocytosis (lose a little bit of RBC membrane- not biconcave, no area of central pallor)

-splenomegaly (due to increased spleen activity)

May partially activate complement- CB3 (opsonin) coated  cells removed by macrophages

If ab is a strong activator of complement--> trigger membrane attack complex--> hemolysis-->more acute/severe disease. 



high concentration of IgG or warm reactive IgM antibodies--> autoagglutination

clumping of RBCs-- IgM can hold many red cells



Slide agglutination test

demonstrates presence of antibody on red cells

differentiates rouleaux formation and autoagglutination. if it's IgM, will stay clumped in saline



Direct coombs test

blood sample with IMHA: antibodies shown attached to antigens on surface

AB that's been raised to CB3 and IgG on red cells

positive test result: rbcs agglutinate


Anemias of decreased red cell production

Secondary anemias: nutritional deficiency; inflammatory disease; chronic renal failure

Primary hypoplastic/aplastic anemias: bone marrow problem 


Nutritional deficiency anemia

protein deficiency (starvation)

mineral deficiencies (iron, copper, cobalt)

vitamin deficiency (B12, folate)

seldom cause anemia in domestic species except for iron deficiency. 


Iron deficiency anemia

can be regenerative or non-regenerative

Iron is an essential component of haem

iron deficiency interferes  with hemoglobin production.

results in production of hypochromic microcytes (red cells with decreased amounts of Hb-->much larger area of central pallor)

Microcytes=small cells, likely seen because RBCs and Hb production is normally together and if we have decreased Hb d/t decreased iron, RBCs stay longer in BM and undergo another replication-->smaller. 


Causes of irona deficiency anemia

Decreased iron intake: fast growing, large breed dogs, suckling piglets (intensive indoor pigs who can't root around in soil. also, sow milk low in iron)

Chronic blood loss: GI ulceration or neoplasia, inflammatory GI disease, parasites, clotting disorders. 


Anemia of inflammation

v. common; multifactorial process

Mild to moderate non-regenerative anemia (normocytic, normochromic)

May be due to longstanding process- infectious, malignant, or other

Functional iron deficiency- not a lack of iron, just not able to use it

Some cytokines may inhibits EPO production or BM progenitor cells directly

nb: TNF can cause macrophages to sequester iron. 


Anemia secondary to renal disease

functional marrow failure due to reduced EPO levels

Other potential factors: anemia of inflammation; uremic toxins- kidneys filter blood, lots of metabolite toxins can have suppressive effect

Normocytic, normochromic 


Primary hypoplastic/aplastic anemias

Celluarity of bone marrow is reduced

may involve multiple cell lines (erythrocytes, granulocytes, platelets)= aplastic anemia

or may only affect red blood cell line=pure red cell aplasia. 


Pure red cell aplasia


immune-mediated: ABs against red cells or progenitor cells in BM

Infectious: FeLV

Vaccine related

EPO replacement failure: in renal failure, can use recombinant human EPO- body develops ABs against own and human EPO

Pre-luekmic conditions. 


Classic aplastic anemia


drugs, chemical (some chemo agents have a myelo-suppressive effect) 


infectious agents- FeLV

pancytopenia develops 



reduction or absence of all blood cell lines

development usually gradual starting with cells with shorter lifespan

eg. granulocytes>platelets>erythrocytes

selective depression of one or two lineages may occur

examples: bracken poisnoning in cattle

estrogen, sulphadiazine

ehrlichia, parvo, felv

bleeding calf syndrome (association with mucosal dz vax)



increase in all cells of circulation/increased red cells in circulation

abnormally increased red cell mass (Increased RBC, HCT/PCV,Hb)

absolute or relative

absolute polycythaemias can be: primary (not controlled by EPO) or secondary (due to increased EPO production)


Relative polycythaemia

most commonly encountered form

increased RBC, PCV and Hb concentration due to decreased plasma volume--> dehydration


splenic contraction in exciteable animals

=transient form (esp. in horses and dogs)


Absolute primary polycythaemia

increased red cells being produced

aka: polycythaemia vera

uncontrolled expansion of red cell mass (not directed by EPO)

chronic myeloproliferative disorder

VERY RARE in animals 


Secondary absolute polycythaemia

excess epo production: appropriate and non-appropriate

Appropriate: hypoxia is fundamental stimulus to EPO. causes of chronic hypoxia include: CV disease and chronic respiratory disase

Inappropriate: no hypoxia and EPO is produced uncontrollably: kidney neoplasms or non-neoplastic disorders e.g. cysts; other non-renal neoplasms. 


Example of presentation of polycythemia

Polycythaemic conjunctiva; mucous membranes hyperemic due to massive increase in number of red cells.

Some cyanosis to mucous membrane edges-->blood viscosity has increased hugely, therefore perfusion to some places has decreased. 


Clinical signs of polycythaemia

Relative: look for signs of dehydration

-tacky mucous membranes, sunken eyes, increased skin tent


neurologic (hyperviscosity- not perfusing properly)

weakness- muscles not perfused


signs attributable to underlying process (if secondary, e.g. chronic lung disease etc).