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ERYTHROCYTE (RBC) DISORDERS: P OLYCYTH A EMIA AND ANAEMIA

H a ematology. ERYTHROCYTE (RBC) DISORDERS: P OLYCYTH A EMIA AND ANAEMIA. OVERVIEW. 1. Polycyth a emia (erythrocytosis) 2. An a emia - Regenerative: blood-loss or h a emolytic - Non-regenerative: primary or secondary bone marrow disorder. 1. POLYCYTH A EMIA/ ERYTHROCYTOSIS.

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ERYTHROCYTE (RBC) DISORDERS: P OLYCYTH A EMIA AND ANAEMIA

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  1. Haematology ERYTHROCYTE (RBC) DISORDERS: POLYCYTHAEMIA AND ANAEMIA

  2. OVERVIEW 1. Polycythaemia (erythrocytosis) 2. Anaemia -Regenerative: blood-loss or haemolytic -Non-regenerative: primary orsecondarybone marrow disorder

  3. 1.POLYCYTHAEMIA/ ERYTHROCYTOSIS

  4. 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) causing • adrenaline secretion, splenic contraction and transient • redistribution of RBC from the spleen to the circulation.

  5. DEFINITION AND TYPES • Absolute (real increase in RBCs) • •Secondary: • - chronic tissue hypoxia: heart/lung diseases, high altitude • - renal tumor or cystsincreasing erythropietin (EPO) secretion • •Primary: • - polycythaemia vera (rare myeloproliferative disorder of RBC • precursors)

  6. 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

  7. 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

  8. 2. ANAEMIA

  9. TYPES OF ANAEMIA haemolytic regenerative haemorrhagic Anaemia secondary B-M disorders non regenerative primary B-M disorders

  10. ANAEMIA A decrease in PCV, Hb concentration and/or RBC count Low PCV

  11. 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

  12. ANAEMIA: CLINICAL IMPLICATIONS -Signs which may be associated with cause of anaemia •icterus •bleeding (petechiae,ecchymoses, melena, haematuria, haematomas) •fever •splenomegaly

  13. TYPES OF ANAEMIA haemolytic regenerative haemorrhagic Anaemia secondary BM disorders non regenerative primary B-M disorders

  14. REGENERATIVE ANAEMIA Characterized by an increase in the number of RETICULOCYTES produced by the bone marrow to compensate for the anaemia.

  15. SIGNS OF REGENERATIVEANAEMIA Reticulocytosis will produce: - MCV and RDW,  MCH and MCHC - In blood smears with Romanowsky stains: • polychromasia • anisocytosis

  16. TYPES OF ANAEMIA haemolytic regenerative haemorrhagic Anaemia secondary BM disorders non regenerative primary B-M disorders

  17. HAEMORRHAGICANAEMIA Plasma total protein generally  (because protein is lost together with RBC) Plasma clear

  18. HAEMORRHAGIC (blood-loss)ANAEMIA • ACUTE BLOOD LOSS • Reticulocyte response will only be detectedin blood after 3-4 days !! • Causes: • •Trauma, surgery • •Coagulation disorders • •Others

  19. CHRONIC BLOOD LOSS - External. Causes: •Gastrointestinal ulceration and tumours •Parasitism In many cases signs of RBC regeneration are present in blood but progressive depletion of iron stores may produce IRON DEFIENCY ANAEMIA with: -normo to microcytosis -hypochromasia -↑ platelet count -reticulocytes can decrease - Internal: blood loss into abdomen/chest

  20. IRON DEFICIENCY ANAEMIA

  21. TYPES OF ANAEMIA haemolytic regenerative haemorrhagic Anaemia secondary B-M disorders non regenerative primary B-M disorders

  22. HAEMOLYTICANAEMIA 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

  23. IN REGENERATIVE ANAEMIAS: TPP and plasma colour can be used to differentiate haemolysis and haemorrhage Haemolytic anaemia Haemorrhagic anaemia TPP > 60 g/L PLASMA ICTERIC/ HEMOLYSED TPP < 60 g/L PLASMA CLEAR

  24. HAEMOLYTICANAEMIA Clinical signs associated with an increase in haemoglobin catabolism: • Haemoglobinemia and haemoglobinuria • Icterus Icteric tissues when serum bilirubin levels >50mol/L Icteric serum when serum bilirubin levels >20mol/L

  25. HAEMOLYTICANAEMIA Red blood cell lysismay occur by two mechanisms: 1.INTRAVASCULAR HAEMOLYSIS 2. EXTRAVASCULAR HAEMOLYSIS

  26. INTRAVASCULAR HAEMOLYSIS (causes) • -Parasites/infectious causes • Vascular Endothelial Lesions • Oxidant damage • - Others

  27. INTRAVASCULAR HAEMOLYSIS (laboratory findings) In addition to  PCV, TPP within the reference range or  and icteric/hemolysed plasma • -Parasites/infectious causes: Blood smears, Serology/PCR • Vascular Endothelial Lesions: Schistocytes in blood smears • - Oxidant damage: Heinz bodies in blood smears

  28. Heinz bodies Schistocyte

  29. 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

  30. 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

  31. 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

  32. Spherocytosis Autoagglutination

  33. ADDITIONAL TESTS TO CHARACTERIZE • INMUNE-MEDIATED HAEMOLYTIC ANAEMIA: • COOMBS TEST • - ERYTHROCYTE FRAGILITY TEST

  34. 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

  35. ERYTHROCYTE FRAGILITY TEST:BASIS Whole blood in a hypotonic solution (0.55% NaCl) Normal RBCsabsorb 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

  36. TYPES OF ANAEMIA haemolytic regenerative haemorrhagic Anaemia secondary B-M disorders non regenerative primary B-M disorders

  37. 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

  38. 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

  39. NON REGENERATIVE ANAEMIA (laboratory findings) In addition to  PCV and absent/reduced signs of RBC regeneration (reticulocytes) • -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)

  40. 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.

  41. CLASSIFICATION OF ANAEMIAS BASED ON RBC INDICES - Macrocytic-hypochromic (regenerative) - Normocytic-normochromic (non regenerative) - Microcytic-hypochromic or normochromic (iron deficiency)

  42. 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?

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