Clinical Haematology 2 Flashcards
- Define anaemia.
- Define erythrocytosis.
– Define relative erythrocytosis.
– Define absolute erythrocytosis.
- Decrease in red blood cell mass as determined by decrease in erythrocyte concentration in blood as measured by reduced RBC, Hb, HCT, PCV.
- Increase in concentration of erythrocytes in blood as measured by increased RBC, Hb, HCT, PCV.
– Relative = resulting from reduced blood volume (dehydration) i.e. haemoconcentration.
– Absolute = Polycythaemia (increased RBC mass) –> resulting from a genuine increase in red cell mass. LESS COMMON.
Why is anaemia clinically relevant?
Brings about a reduced oxygen carrying capacity.
Brings about a reduced oxygen delivery to the tissues – unable to metabolise properly, with some going into aerobic respiration and others failing.
Identified in the kidneys which produce erythropoietin, stimulating production of more RBCs to bring oxygen carrying capacity and oxygen delivery back up to normal.
What is the clinical presentation of anaemia dependent on?
- Severity.
- Chronicity of development.
- Clinical spectrum – subclinical > non-specific lethargy > exercise intolerance > overt collapse / tachypnoea > death.
- Acute anaemia clinical presentation.
- Chronic anaemia clinical presentation.
- e.g. Haemolytic.
PCV 18%.
Tachycardia, tachypnoea, haemic murmur, weak, barely ambulatory. - e.g. bone marrow disease.
PCV 14%.
Exercise intolerant and lethargic at home, but walked into consult, interactive, still looking for food.
Note: pica – ingestion of inappropriate products e.g. licking concrete, licking walls, eating soil – relates to their desire to try and get hold of iron sources.
What is anaemia generally subdivided into?
Regenerative and non-regenerative.
- What is regenerative subdivided into?
- What is non-regenerative subdivided into?
- How long is the pre-regenerative phase and what is this?
- Haemolysis and haemorrhage.
- Extra-bone marrow disease and primary bone marrow disease. Typically kidney suppressing bone marrow or not producing enough EPO to signal bone marrow production.
- 3-5 days. The period of time where a haemorrhage or haemolysis has occurred and the bone marrow has not yet reacted to this to produce more RBCs.
What can be seen in the increased demand for RBC production?
Reticulocytosis = regeneration.
Reticulocytes are larger and bluer than mature RBCs and are premature and kicked out early in order meet demands.
What are aggregate reticulocytes?
More immature reticulocytes which retain large amounts of ‘aggregates’ of RNA – appear purple when stained. Appear as aggregates when stained with
Mature within 1-2 days in circulation.
Appear as polychromatophils when stained w/ routinely used Rowanowsky-stains (e.g. Wright’s, Giemsa, Diff-Quik etc.
What are punctate reticulocytes?
Mature – retain only small ‘punctates’ or RNA.
Visualisation requires staining w/ intravital dyes.
Only present in cats (not dogs).
– may persist for a few weeks in circulation.
- What is the most regenerative measure of regeneration in dogs and cats?
- What is the case for horses?
- What is the case for cattle/sheep?
- Reticulocyte count.
- Horses retain reticulocytes un the bine marrow and they are not seen in the circulation.
- Cattle/sheep have variable release of reticulocytes, often only see them w/ severe anaemia.
What are other morphological features of regeneration?
Polychromasia (abnormally high number of immature RBCs found in bloodstream due to premature release from bone marrow during blood formation).
Anisocytosis (abnormal variation in size of RBCs).
Nucleated RBCs.
– Other RBC precursors.
- Define normocytic, macrocytic, microcytic respectively.
- Define normochromic, hypochromic, hyperchromic respectively.
- Nirmal mean cell volume, high mean cell volume, low mean cell volume.
- normal mean cell haemoglobin / mean cell haemoglobin concentration, low mean cell haemoglobin / mean cell haemoglobin concentration, high mean cell haemoglobin / mean cell haemoglobin concentration (not possible – artefact due to haemolysis / lipaemia / Heinz bodies).
What happens during erythropoiesis?
RBC become progressively smaller / accumulates Hb.
Hb reaches threshold and nucleus is extruded, cell changes from nucleated RBC to reticulocyte.
If Hb levels continue to decrease, ongoing cell divisions, increasing the time for Hb to accumulate and microcytic cells.
Extreme: inadequate Hb causes hypochromic RBC, iron deficiency with microcytic cells and sometime hypochromic anaemia.
- What happens to RBCs in extravascular haemolysis?
- What happens to RBCs in intravascular haemolysis?
- Which is deemed to be worse?
- phagocytosed primarily in the spleen.
- lyse in circulation due to membrane damage.
- Intravascular due to the degree of damage caused by Hb in circulation at this level.
- What are the clues for haemolysis?
- Haemoglobinaemia (can become haemoglobinuria).
Bilirubinaemia (clinical jaundice / bilirubinaemia).
Ghost cells (remnants of membrane where they have ruptured and release Hb into circulation).
Other RBC morphological changes (Heinz bodies).
If immune-mediated, may have:
- Spherocytes (membrane removed so SA reduced but volume maintained so biconcave lost).
- Autoagglutination (in saline agglutination).
- Positive Coomb’s / Direct Antibody Test (DAT).
Differentials for haemolysis.
- Primary IMHA.
- Infectious agents – haemotropic mycoplasma (mycoplasma haemofelis), babesia canis, FeLV, equine infectious anaemia virus.
- Oxidative damage (Heinz bodies, eccentrocytes).
– Toxins: Allium spp. (garlic etc), paracetamol, zinc, brassicas e.g. cabbage, sprouts (ruminants), red maple leaf (horses).
– Systemic disease. - Hypophosphataemia.
- Neonatal isoerythrolysis.
- Transfusion reactions.
- Microangiopathic disease (shear injury).
- Hereditary RBC enzymopathies (PFK / PK deficiency).
-Other rare causes – envenomation, erythrophagocytic disease.
- What is primary IMHA?
- What is secondary IMHA?
- Autoimmune.
- Secondary to molecular mimicry, haptenisation etc.
– Can be triggered by neoplastic or inflammatory / infectious disease, anywhere in the body (e.g. UTIs).
– Can be triggered by recent drug use.
–> penicillins, cephalosporins, trimethoprim-sulphonamides.
– RBC-associated infection disease w/ variable mechanisms of inducing haemolysis.
–> Intra-cellular parasites.
–> Extra-cellular parasites.
Difference between agglutination and rouleaux formation?
Agglutination is where the RBCs randomly stick together.
Rouleaux formation is where the RBCs stack themselves quite orderly in a line.
– more commonly seen in animals w/ high globulin levels.
– NOT autoagglutination (where ABs stick to red cells.
- What does Coomb’s testing evaluate?
- In what cases is Coomb’s testing pointless and why?
- Sensitivity / specificity? – how is this combatted?
- Coomb’s reagent?
- Coomb’s testing technique?
- For presence of antibody and/or complement on RBC surface.
- Clinically pointless if in saline autoagglutination present as we know it will be positive.
- Far from perfect w/ false positives and false negatives – interpret result in light of the patient.
- Species-specific antibody directed against IgG, IgM, or complement.
- Patient’s RBCs are washed and mixed w/ serial dilutions of Coombs’ reagent (at 4C and 37C).
The highest dilution at which agglutination occurs is reported.
Clinical approach to IMHA.
Confirm diagnosis.
- Regenerative anaemia w/ evidence of haemolysis.
- AND spherocytes (evidence of attack of RBC surface) and/or autoagglutination or Coombs’ positive.
History.
- Recent drug administration?
- Travel?
Screen for systemic neoplastic / inflammatory / infectious disease.
- Thoracic radiographs.
- Abdominal ultrasound.
- ECG (w/ suspicion of endocarditis).
- Culture / PCRs (Babesia spp., haemotropic mycoplasmas esp. in cats) / serology.
Neonatal isoerythrolysis in cats.
Naturally occurring, clinically significant, alloantibodies.
Typically type B mum w/ type A kittens.
Colostrum – type B mum always has strong anti-A antibodies in plasma – secreted into colostrum. Typically where type A tom cat and type B queen have mated.
Erythrocyte surface antigens are genetically-mediated.
Haemolysis occurs when type A or AB kittens ingest colostrum from type B queen (i.e. containing anti-A antibodies).
Haemolysis and associated signs (jaundice etc.) occur within hours to days of ingestion.
Prevent by managed mating (blood-typing queen/tom) or blood typing kittens prior to first feed.
- What types of internal haemorrhages are there?
- What type of external haemorrhages are there?
- What is melena?
- Haemothorax, haemoabdomen.
- Body surface (clearly visible).
From external surfaces (hidden) – often associated with GIT, genitourinary tract, respiratory tract. - Digested / changed faeces that is passed in the faeces, making it appear dark and sticky.
What to consider when dealing with haemorrhage.
Is it global?
- Bleeding diathesis (coagulopathy, thrombocytopenia, fibrinolysis).
Primary pathology at the site of haemorrhage.
- Trauma.
- Neoplasia.
- Inflammation (e.g. ulcer).
- Idiopathic.
Causes of body cavity haemorrhage.
Secondary haemostatic disorder i.e. coagulopathy.
- Lack of clotting factors.
– Acquired e.g. rodenticide intoxication, angiostrongylosis, liver disease.
– Congenital e.g. haemophilia.
Primary pathology within the body cavity.
- Traumatic.
- Non-traumatic.
– Abdominal –> splenic»_space; hepatic (» renal, adrenal, other). Ryptured splenic malignancy most common.
– Thoracic (less common than abdominal).
–> Thymic involution (adolescent) (benign) vs neoplasia.
