erythrocyte (rbc) disorders: polycythaemia and anaemia haematology
TRANSCRIPT
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ERYTHROCYTE (RBC) DISORDERS: POLYCYTHAEMIA AND ANAEMIA
Haematology
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OVERVIEW
1. Polycythaemia (erythrocytosis)
2. Anaemia
-Regenerative: blood-loss or haemolytic
-Non-regenerative: primary or secondary bone
marrow disorder
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1.POLYCYTHAEMIA/ERYTHROCYTOSIS
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DEFINITION AND TYPES
An increase in PCV, Hb concentration and/or RBC count
-Relative • Dehydration (eg. increased water loss: e.g. vomiting,
diarrhoea, polyuric disorders) causing an apparent increase in RBC due to a decrease in fluid in circulation.
• Exercise, fear, excitement (eg. in the horse) causingadrenaline secretion, splenic contraction and transientredistribution of RBC from the spleen to the circulation.
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-Absolute (real increase in RBCs)
• Secondary:
- chronic tissue hypoxia: heart/lung diseases, high altitude
- renal tumor or cysts increasing erythropietin (EPO) secretion
• Primary:
- polycythaemia vera (rare myeloproliferative disorder of RBC
precursors)
DEFINITION AND TYPES
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CLINICAL IMPLICATIONS
-Cardiovascular signs due to blood hyperviscosity and
peripheral hypoxia (increased pulse and
respiratory rate)
-Neurological signs (syncope, lethargy) due to poor brain
perfusion, and bleeding tendencies
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LABORATORY DIAGNOSIS OF DIFFERENT CAUSES
-Relative
• Dehydration: total protein and albumin
-Absolute
• Secondary to chronic hypoxia: arterial pO2
• Renal tumours or cysts (or others): erythropoietin EPO*)
• Polycythaemia vera: EPO
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2. ANAEMIA
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TYPES OF ANAEMIA
Anaemia
regenerative
nonregenerative
haemolytic
haemorrhagic
secondary B-M disorders
primary B-M disorders
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ANAEMIA
A decrease in PCV, Hb concentration and/or RBC count
Low PCV
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ANAEMIA: CLINICAL IMPLICATIONS
- Inadequate tissue oxygenation • pale mucous membranes
• weakness, inappetance, anorexia • syncope
- Compensatory mechanisms • tachypnoea (particularly if forced to exercise) • tachycardia, small and strong pulse
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-Signs which may be associated with cause of anaemia • icterus • bleeding (petechiae,ecchymoses, melena, haematuria, haematomas)
• fever • splenomegaly
ANAEMIA: CLINICAL IMPLICATIONS
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TYPES OF ANAEMIA
Anaemia
regenerative
nonregenerative
haemolytic
haemorrhagic
secondary BM disorders
primary B-M disorders
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REGENERATIVE ANAEMIA
Characterized by an increase in the number of
RETICULOCYTES produced by the bone marrow to
compensate for the anaemia.
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SIGNS OF REGENERATIVE ANAEMIA Reticulocytosis will produce:- MCV and RDW, MCH and MCHC- In blood smears with Romanowsky stains: • polychromasia • anisocytosis
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TYPES OF ANAEMIA
Anaemia
regenerative
nonregenerative
haemolytic
haemorrhagic
secondary BMdisorders
primary B-M disorders
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HAEMORRHAGIC ANAEMIA
Plasma total protein generally (because protein is lost together with RBC)
Plasma clear
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-ACUTE BLOOD LOSS
Reticulocyte response will only be detected in blood
after 3-4 days !!
Causes:
• Trauma, surgery
• Coagulation disorders
• Others
HAEMORRHAGIC (blood-loss) ANAEMIA
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- External. Causes:• Gastrointestinal ulceration and tumours • Parasitism
-normo to microcytosis-hypochromasia- ↑ platelet count-reticulocytes can decrease
CHRONIC BLOOD LOSS
- Internal : blood loss into abdomen/chest
In many cases signs of RBC regeneration are present in blood but progressive depletion of iron stores mayproduce IRON DEFIENCY ANAEMIA with:
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IRON DEFICIENCY ANAEMIA
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TYPES OF ANAEMIA
Anaemia
regenerative
nonregenerative
haemolytic
haemorrhagic
secondary B-M disorders
primary B-M disorders
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HAEMOLYTIC ANAEMIA
Plasma total protein within reference range or Plasma can be icteric or hemolysed
Abnormal erythrocyte morphology (Heinz bodies, RBC parasites, spherocytes) may suggest a haemolytic cause for
the anaemia
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IN REGENERATIVE ANAEMIAS:TPP and plasma colour can be used to differentiate haemolysis and haemorrhage
Haemorrhagic anaemia Haemolytic anaemia
TPP < 60 g/L
PLASMA CLEAR
TPP > 60 g/L
PLASMA ICTERIC/
HEMOLYSED
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HAEMOLYTIC ANAEMIA
Clinical signs associated with an increase in haemoglobincatabolism: • Haemoglobinemia and haemoglobinuria • Icterus
Icteric serum when serum bilirubin levels >20mol/L
Icteric tissues when serum bilirubin levels >50mol/L
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HAEMOLYTIC ANAEMIA
Red blood cell lysis may occur by two mechanisms:
1. INTRAVASCULAR HAEMOLYSIS
2. EXTRAVASCULAR HAEMOLYSIS
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INTRAVASCULAR HAEMOLYSIS (causes)
-Parasites/infectious causes
-Vascular Endothelial Lesions
-Oxidant damage
- Others
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INTRAVASCULAR HAEMOLYSIS (laboratory findings)
- Parasites/infectious causes: Blood smears, Serology/PCR
-Vascular Endothelial Lesions: Schistocytes in blood smears
- Oxidant damage: Heinz bodies in blood smears
In addition to PCV,TPP within the reference range or
and icteric/hemolysed plasma
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Heinz bodies
Schistocyte
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EXTRAVASCULAR HAEMOLYSIS
-Physiological. (aged erythrocytes) removed by the
macrophage-monocyte system in the spleen
-Pathological. (Auto)antibodies are produced against
“normal” erythrocytes that are phagocytosed by the spleen
- INMUNE-MEDIATED HAEMOLYTIC ANAEMIA
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INMUNE-MEDIATED HAEMOLYTIC ANAEMIA
- Idiopathic (unknown mechanisms) - Secondary to: • Infectious agents • Drugs/insecticides/vaccines/neonatal isoerythrolysis
CAUSE THE APPEARANCE OF ABNORMAL ANTIGENS ON THE ERYTHROCYTE
CELL MEMBRANE
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INMUNE-MEDIATED HAEMOLYTIC ANAEMIA (laboratory findings)
In addition to PCV, TPP = within the reference range or
and yellow coloured plasma
Spherocytosis (canine blood)Autoagglutination
Gross autoagglutination on a slide
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Spherocytosis Autoagglutination
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ADDITIONAL TESTS TO CHARACTERIZEINMUNE-MEDIATED HAEMOLYTIC ANAEMIA:
-COOMBS TEST
- ERYTHROCYTE FRAGILITY TEST
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COOMBS TEST
Detects antibodies directed at the erythrocyte membrane
Falses +´s: -some chronic infections - “ parasites (heartworms, haemobartonella) - “ drugs (trimethoprim-sulfa) - “ neoplasms
Falses -´s: in some cases of inadequate antibody production
The test is species-specific
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Whole blood in a hypotonic solution (0.55% NaCl)
Normal RBCs absorb water from the hypotonic solution for osmotic equilibrium and are distended but not haemolyzed
Membranes of fragile RBCs (spherocytes, and those with enzyme deficiencies or damaged by some drugs) cannot withstand distension and are haemolyzed
ERYTHROCYTE FRAGILITY TEST:BASIS
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TYPES OF ANAEMIA
Anaemia
regenerative
nonregenerative
haemolytic
haemorrhagic
secondary B-M disorders
primary B-M disorders
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NON-REGENERATIVE ANAEMIA
Characterized by an absence of, or reduction in reticulocyte response in an anaemic animal.
This will produce:
• Normocytic-normochromic anaemia MCV and RDW, MCH and MCHC within the reference ranges
• In blood smears with Romanowsky stains: - absence of polychromasia and anisocytosis
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NON REGENERATIVE ANAEMIA (causes)
- Primary bone marrow disorders:• some myeloproliferative, lymphoproliferative and
myelodisplastic disorders
• virus (feline leukaemia/ canine parvovirus)
• some drugs: oestrogens, inmunosuppressive agents,
non-steroid anti-inflammatories
- Secondary: •chronic inflammatory disease, some endocrine diseases
•chronic renal failure with decreased erythropoietin levels
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NON REGENERATIVE ANAEMIA (laboratory findings)
- Primary (bone marrow disorders): Diagnosis by bone marrow evaluation + specific tests. Leukopenia and/or thrombocytopenia may also occur
- Secondary: Laboratory findings of the primary disease. (e.g. chronic renal failure: BUN and creatinine)
In addition to PCV and absent/reduced signs of RBC regeneration (reticulocytes)
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NON REGENERATIVE BLOOD SMEARS MAY BE SEEN IN HAEMORRHAGE OR
HAEMOLYSIS IF:
- RBC loss or destruction has occurred within the previous 4
days
- chronic haemorrhage has induced iron deficiency anaemia
- animals with a low reticulocyte response: bovine, and
particularly equine species. In the latter, the only sign that
regeneration is occurring may be a small increase in MCV.
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CLASSIFICATION OF ANAEMIASBASED ON RBC INDICES
- Macrocytic-hypochromic (regenerative) - Normocytic-normochromic (non regenerative) - Microcytic-hypochromic or normochromic (iron deficiency)
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DIAGNOSIS OF ANAEMIAS: SUGGESTED APPROACH
The following questions must be addressed:
1. Regenerative or non-regenerative?
2. If regenerative: haemolytic or haemorrhagic?
3. If non-regenerative: primary or secondary bone
marrow disorder?