Haematology 2 Flashcards
ANAEMIA
ANAEMIA
A reduction in erythrocyte number AND/OR haemoglobin concentration.
ie. Decreased RBC, HCT (haematocrit)/PCV (packed cell volume), and/or Hb.
NOT a final diagnosis- the underlying cause must be found.
ACUTE ANAEMIA
Sudden onset, severe.
- Pallor
- Tachycardia
- Muscular weakness
- Subnormal temperature
- Coma
- Death
CHRONIC ANAEMIA
Longer duration.
- Fatigue/lethargy
- Exercise intolerance
- Tachycardia
- Fainting
- Pallor
- Cardiac murmur (decrease in blood viscosity causes increased turbulence)
WHAT CAUSES ANAEMIA?
- Decreased erythrocytes entering blood (eg. Decreased erythrocyte production, bone marrow issue)
- Increased exit of erythrocytes from blood.
If bone marrow is functioning NORMALLY, we see a 3-5 day preregenerative phase, then a REGENERATIVE PHASE where increased numbers of reticulocytes are seen in the blood.
TYPES OF ANAEMIA
- REGENERATIVE
2. NON REGENERATIVE
REGENERATIVE ANAEMIA
Caused by haemolysis (intravascular or extravascular) or haemorrhage (internal or external).
Characterised by:
- INCREASED RETICULOCYTES IN BLOOD- not horses!
- MACROCYTIC- RBCs are larger than normal (increased MCV)
- HYPOCHROMIC- decreased Hb concentration due to increased size.
- INCREASED POLYCHROMASIA/ANISOCYTOSIS- Increased number of reticulocytes (polychromatic red cells), variable size of cells.
- NUCLEATED RED CELLS are sometimes seen (eg. normoblasts). These are not the best way to decide if anaemia is regenerative or not- use reticulocyte presence.
- BASOPHILIC STIPPLING of RBCs can be seen in cattle.
HAEMORRHAGIC ANAEMIA
REGENERATIVE.
Seen after blood loss (acute/chronic/coagulopathy), can be INTERNAL OR EXTERNAL.
Marrow response will differ depending on internal or external haemorrhage.
BLOOD FINDINGS- normal in first few days- preregenerative phase (3-5 days).
-Regenerative phase- polychromasia, anisocytosis, HJ bodies, thrombocytosis, neutrophilia, MACROCYTIC HYPOCHROMIC.
POLYCHROMASIA
Increased polychromatic red cells- RETICULOCYTES
ANISOCYTOSIS
Variable size of red cells.
HJ BODIES
Howell-Jolly bodies- fragments of basophilic nuclei within erythrocytes.
THROMBOCYTOSIS
Increased platelets in blood
NEUTROPHILIA
Increased neutrophils in blood.
MACROCYTIC/HYPOCHROMIC
Characteristic of regenerative anaemias.
Macrocytic- Increased mean cell volume (MCV)/cell size.
Hypochromic- Decreased MCH/MCHC due to increased cell size. Gives cells an increased area of central pallor.
(red blood cells)
DEGREE OF REGENERATION- HAEMORRHAGIC ANAEMIA
Degree of regeneration depends on:
-Severity of blood loss- more severe= more marrow stimulation= more regeneration.
-Location of bleeding:
INTERNAL (eg. in to body cavities)- iron is available for Hb synthesis, so greater regeneration is seen.
EXTERNAL (eg. GI, urinary tract bleed)- RBCs and thus iron are lost, so less regeneration is seen.
PROTEIN is also lost -> hypoproteinaemia (classically PANHYPOPROTEINAEMIA- decreased PLASMA proteins)
HAEMOLYTIC ANAEMIA
REGENERATIVE.
2 important features: Reduced RBC survival time,
iron from destroyed RBCs is RETAINED IN THE BODY.
This means that haemolytic anaemia is VERY REGENERATIVE, as iron can be reused.
Red cells can be EXTRAVASCULARLY or INTRAVASCULARLY lysed.
EXTRAVASCULAR LYSIS
One of the methods of RBC destruction seen in haemolytic anaemia.
Splenic enlargement.
Iron and globin reutilised.
Haem transferred to bilirubin.
Can see jaundice.
Otherwise bilirubin is excreted in bile after conjugation with glucuronides.
INTRAVASCULAR LYSIS
Red cells are lysed in circulation.
This means there is free Hb in the blood- haemoglobinaemia.
Jaundice can be seen by binding of Hb with haptoglobins and subsequent phagocytosis.
Saturation of haptoglobins leads to Hb being seen in the kidneys.
-> HAEMOGLOBINURIA
-> Toxic nephrosis.
HAEMOGLOBINURIA
Hb in urine gives red colour.
This persists after centrifugation, unlike the red colour seen with haematuria (bleeding in to GI tract leaves sediment in urine)- colour disappears after centrifugation.
CAUSES OF HAEMOLYTIC ANAEMIA
- INHERITED- rare.
eg. Phosphofructokinase deficiency in Springer Spaniels.
Pyruvate kinase deficiency in basenjis. - ACQUIRED:
- Infectious agents.
- Oxidative compounds.
- Fragmentation.
- Immune mediated.
INFECTIOUS HAEMOLYTIC ANAEMIA
eg. Mycoplasma- red/magenta dots on RBCs, seen histologically.
Detected by macrophages -> ingestion.
May be transmitted by fleas.
Often an opportunistic infection eg. Mycoplasma haemofelis is seen in cats with FeLV.
Babesiosis and others, depending on parts of the world.
TOXIC AND OXIDATIVE HAEMOLYTIC ANAEMIA
Oxidative agents in drugs/chemicals can reduce GLUTATHIONE levels in red blood cells.
Haem iron can be oxidised to methaemoglobin.
Oxidative damage to Hb causes HEINZ BODY formation.
Affected blood cells are then destroyed by intra or extravascular lysis.
Cats are predisposed to toxic/oxidative haemolytic anaemia due to the structure of their Hb.
HEINZ BODIES
Pale circular areas on RBC.
FRAGMENTATION HAEMOLYTIC ANAEMIA
Seen when RBCs are subject to excessive TRAUMA.
Features of intravascular lysis may be present.
SCHISTOCYTES- broken RBCs. Shredded, torn by severe mechanical trauma.
ACANTHROCYTES- torn up RBCs, but are still intact. Crenated.
IMMUNE MEDIATED HAEMOLYTIC DISORDERS
Antibodies are involved in red cell destruction.
- BLOOD GROUP INCOMPATIBILITIES (eg. blood transfusion reactions, neonatal isoerythrolysis)
- IMMUNE MEDIATED HAEMOLYTIC ANAEMIA- generated against self antigen/own red cells.
NEONATAL ISOERYTHROLYSIS
Haemolytic disease of the newborn.
Seen because mother has different blood group to young’s (young has inherited sire’s blood group)
AND MOTHER HAS BEEN PREVIOUSLY SENSITISED TO THAT GROUP (eg. she has had previous offspring with that blood group/vaccination/blood products)
Maternal blood group alloantibodies are absorbed from the colostrum, destroying the neonate’s RBCs
(via phagocytosis and intravascular lysis)
Neonate is normal at birth, but weakness etc. develops 12-48 hours after birth, as it obtains colostrum.
.
Treat by STOPPING FOAL FROM SUCKLING (until after ~48 hours when colostrum will no longer be absorbed from gut. This will compromise immunity; will have to obtain antibodies another way)
DETECTION OF NEONATAL ISOERYTHROLYSIS
INDIRECT COOMB’S TEST.
Plasma from mare is incubated with red cells from stallion.
Antibodies are produced and attach.
Mixing of other antibody -> AGGLUTINATION.
IMMUNE MEDIATED HAEMOLYTIC ANAEMIA IN ADULTS
- Primary/autoimmune- idiopathic. Antibodies are produced against own red blood cells.
- Secondary- caused by an underlying trigger eg. drugs/toxins, infectious agents, neoplasia, vaccines (?)
WHAT KIND OF IMMUNE MEDIATED HAEMOLYTIC ANAEMIA IS NORMALLY SEEN IN DOGS?
Primary/idiopathic.
In other species, immune mediated haemolytic anaemia is uncommon, and normally secondary.
CANINE AUTOIMMUNE HAEMOLYTIC ANAEMIA
Antibodies are produced against dog’s own RBCs.
IgM pentamers or IgG monomers.
Autoantibodies:
AGGLUTININS- cause clumping
LYSINS- cause lysis
INCOMPLETE- cause incomplete activation of the complement cascade.
Warm reacting- works at body temperature.
Cold reacting- works at colder temperatures.
WARM ANTIBODY AIHA
Incomplete IgG coats RBC.
It loses surface area and becomes a SPHEROCYTE (because it is too small to form biconcave shape)
-> complete or partial phagocytosis in spleen.
Splenomegaly.
May partially activate complement.
C3b- opsonin, enhances phagocytosis.
Complement only activated to level of C3b.
C3b coated cells will be removed by macrophages.
If antibody is a STRONG activator of complement, HAEMOLYSIS and more ACUTE/SEVERE disease will be seen.
(Membrane Attack Complex- lyses cell, Hb spills out in to plasma)
AUTOAGGLUTINATION
Caused by high concentration of IgG or warm reactive IgM antibodies —> AGGLUTINATION of RBCs (clump together)
SLIDE AGGLUTINATION TEST
Drop of saline on slide, then drop of blood.
If there is ANTIBODY present on the RBCs, there will be agglutination- cells will remain clumped, giving a gritty/sandy appearance.
If there is rouleaux formation (no antibody), the cells will disperse in saline, dercreasing viscosity- no agglutination.
DIRECT COOMBS TEST
Used to detect if antibody (IgG) or complement protein (C3b- incomplete) have bound to RBCs in vivo.
Sample is taken and washed to remove serum proteins from RBCs.
Sample is centrifuged with antibodies against IgG and C3b.
If IgG/C3b have become bound to RBCs in vivo, antibodies will AGGLUTINATE the RBCs.
This is a positive result.
