Clinical Pathology- Haematology: Anaemia Flashcards
What is the definition of anaemia?
Reduction in RBC mass
Value below reference interval for any of: PCT/Hct, RBC, total Hb
What causes anaemia?
Inadequate production by the bone marrow
Increased destruction
Loss (haemorrhage)
Typically which causes of anaemia are regenerative and non-regenerative?
Inadequte production from bone marrow- non-regenerative
Increased destruction- usually regenerative
Loss (haemorrhage)- regenerative but not enough,
What are the responses to anaemia?
2-3 diphosphoglycerate (2,3-DPG) increases in erythrocytes which lowers oxygen-Hb affinity causing better O2 delivery to peripheral tissues
Alterations in tissue perfusion- increased EPO, stimulates bone marrow to increase eryhtropoiesis
Alterations in behavious to reduce oxygen requirment
Why can cats respond to anaemia better?
Cats have different oxygen affinity haemoglobins- changing levels of these gives them a mix of Hbs able to response over a range of oxygenation conditions
What are the clinical signs of anaemia?
Pallor
Weakness
Excercise intollerance
Tachycardia
Tachypnoea
‘Haemic’ murmur- more viscous blood creating more sound
What history should be collected from an anaemic animal?
Signalment
Acute or chronic onset of signs
Weakness, lethargy, excercise intolerance
Evidence of external blood loss
Access to toxins, recent drug therapy
Urine normal?
Abroad?
What should be checked in a physical examination when anaemia is suspected?
Pallor, weakness
Tachycardia, bounding or hyperkinetic pulse
Tachypnoea, dyspnoea
Haemic murmur
Icterus
Petechiation
Evidence of bleeding
Pyrexia
Lymphadenopathy
Abdominal pain/mass
Splenomegaly
What tests can be done on a potentially anaemic animal?
Full haemoatology- reticulocyt count required
TP, alb, glob
Coag screen/bleeding times
Saline agglutination/Coombs test
Biochem
Urinalysis
Diagnostic imaging
What degrees of severity are there for anameia based on PCT/Hct?
Mild- 30-60% in dogs, 20-24% in cats
Moderate- 18-28% in dogs, 15-19% in cats
Severe- <18% in dogs, <15% in cats
What erythrocyte indexed and regenerative response can be used for classification of anaemia?
Erythrocyte indexes- MCV, MCHC (mean corpiscular volume, mean haem concentration):
Microcytic/normocytic/macrocytic/hypochromic/normochromic
Regenerative responses- regenerative vs non-regen
What are hallmarks of regenerative anaemia?
Reticulocytosis and polychromasia
How can polycromatophils and reticulocytes be seen?
Identify the polychromatophils and reticulocytes in the images?
Poly chromatophils seen with routine romanowsky stains
Reticulocytes are seen with ‘special stains’- new methylene blue
Large red are polychromatophils
RBCs with blue are reticulocytes- shows ribosomes
All flowers are roses but not all roses are flowers
Sub in polychromatophils and reticulocytes
All polychromatophils are reticulocytes but not all reticulocytes are polychromatophilic
How long does it take for reticulocytes to increase after anaemia?
Initially anaemia will appear non-regenerative
What are the main causes of regenerative anaemias?
Haemorrhage
Haemolysis
What types of reticulocytes do feline have?
Aggregate and punctate (less stained) which last up to 10 days before reaching mature RBC
How can an acute haemorrhage be identified?
Results in hypovolaemic shock
Proportional loss of all blood components
Presents as- pallor, tachycardia, weak peripheral pulses, poor peripheral perfusion, cold extremities
How much blood loss can often lead to fatality?
>30%
How does PCV and TP vary with acute haemorrhage?
Immediatley PCV is 45% lost in proportion
24 hours later PCV drops to 30% adn TP drops as interstitial fluid moves into circulation
What is required for chronic blood loss?
Bleeding for >2 weeks
What can chronic blood loss lead to?
Iron deficiency anaemia- IDA after consumption of iron stores
Iron stores are abundant in adults so it takes > 1 month
Initially regenerative
What does IDA cause to happen to RBCs?
The extra division of the precursor in attempt to reach the optimal cytoplasmic haemoglobin concentration as not enough can be produced leadining to microcytic hypochromic RBC being produced
1) What usually causes IDA?
2) What else can cause IDA?
3) How can it be diagnosed?
1) Most common cause is chronic bleeding- NSAIDs, steroids, neoplasia, Ulcers, CRF, parasitic infections
2) Dietary deficiency- rare (puppies, kittens slow to tansfer to solid food, vegan diet)
3) Microcytic and hypochromic anaemia
What are the different arrows pointing to in this image?
What kind of anaemia is this?
Iron deficiency anaemia
What is the name for increased destruction of RBCs, what are the two types?
Haemolysis
Immune mediates
Non-immune mediated
What can cause immune-mediated and non-immune mediated haemolysis?
Immune mediated:
immune-mediated- primary or secondary to infecion/neoplasia
Non-immune mediated:
Oxidative damage- onions, paracetamol in cats, zinc
Intra-erythrocytic parasites
Mechanical damage- angiopathic anaemia
What is the most common cause of haemolysis and why does it happen?
Immune mediated haemolytic anaemia
Production of antibodies against patiensts red blood cells by macrophages or complement system involvment
Describe the process of extravascular haemolysis
Antibody binds to RBC and macrophage binds and phagocytosis of RBC
Spherocytes arise from partial phagocytosis
Haem converted to unconjugated bilirubin
Unconjugated bilirubin conjugated by liver and excreted with bile
Why can extravascular haemolysis result in jaundice?
If liver capacity is over whelmed from conjugated bilirubin it can lead to hyperbilirubinaemia as well as bilirubinuria and jaundice
What are the clinical signs of extravascular haemolysis?
Variable onset and severity of signs
Pallor
Lehtargy
Tachycardia, tachypnoea
Splenomegaly
Mild lymphadenopathy
+/- jaundice
How does intravascular haemolysis occur and what does it lead to?
Intravascular cell lysis
Extensive complement activation
Leads to:
Haemoglobinaemia
Haemoglobinuria
Renal compromise- tubular epithelial damage- free haemoglobin
Jaundice
What are the clinical signs of intravascular haemolysis?
Sudden onset- severe illness
Pallor
Collapse
Jaundice
Tachycardia/tachypnoea
Splenomegaly
Haemoglobinuria
How is IMHA diagnosed?
Clinical signs
Haematology-
typically regenerative
autoagglutination
sphertocytes- especially if many
Leukocytosis with left shift
Direct antiglobulin test (coomb’s test)
Demonstration of anti-RBC antibodies
What exceptions are there of regeneerative IMHA?
1/3 of patients present with poorly regenerative anaemia which could be from:
Acute onset (<3-5 days) so pre-regenerative
Immune-targeting of RBC precursors in the bone marrow
What are intravascular hosts a sign of?
Intravascular lysis
What causes autoagglutination and how does it present?
Antierythrocyte IgM
or
Very high antierythrocyte IgG
Appears as red cells cluster as grapes
What is the difference between agglutination of RBC vs Rouleaux formation?
Agglutination- antibody mediated clumping- may be temp dependent, strongly supportive IMHA
Rouleaux formation- stacking of RBCs due to increased plasma proteins coating RBCs- caused bny inflammation, cancer, normal in horse and cats
What is the purpose of the saline agglutination and how is it done?
Rouleaux disappear and agglutinates stay therefore allowing distinguishing
1 drop of anti coagulated +4 or more drops of saline
What is the purpose of the coomb’s test and when can it not be done?
Used to detect presence of antiRBC antiboides and complement RBCs using rabbit antisera
Cannot be done if agglutionation is already evident
How does the alvedia antiglobulin test work and what does it test for?
Immuno-chromatographic technology
Detects for presence of immunoglobulin and/or C3 components binding to RBC surface with a colour change
What are the possible triggers for secondary IMHA?
Drugs
Vaccines
Neoplasia
Inflammatory diseases
Infectious diseases
What tests are for IMHA and what further tests can be done?
Smear checking for autoagglutination
Saline agglutination test
Coomb’s test
Antiglobulin test
Further tests- Biochemistry/urinalysis, Imaging, PCR, PT/aPTT
Describe the biochemistry and urinalysis of IMHA?
Biochem:
Elevated ALT and AP
Hyperbilibrubinaemia
Possible azotaemia
Urinalysis:
Haemoblinuria
Billirubinuria
Proteinuria
What is non-regeneerative anaemia and what are its causes?
Absence of reticulocytes- make sure its not pre-regen
Causes- primary marrow disease, other diseases affecting marrow function, lack of erythropoietin
What can cause intramarrow disease for non-regeneratvie anaemia?
Idiosyncratic drug reactions
Oestrogen toxicity
Pure red cell aplasia
Aplastic pancytopenia
Myelofibrosis/myelosclerosis
Myelodysplastic syndromes
Bone marrow sample required for confirmation
What drugs can give idiosyncratic drug reactions?
Unpredictable individual adverse reactions
Implicated:
Oestrogen
Antibiotics
NSAIDs
Anticonvulsants
Antivirals
antifungals
methimazole
What does oestrogen toxicity cause and how can it be caused?
Causes pancytopenia- thrombocytopenia, neutropenia, anemia
Causesd from exogenous oestrogen or endogenous- sertoli cell tumours
How is oestrogen toxicity treated?
Bactericial antibiotics
Blood/platelet rich transfusions
Removal of offending neoplasm
Prognosis very poor
What is red cell aplasia?
What are its causes and treatment?
Only when red cell line is affected
No erythroid precursors in the BM
Myriad of causes- most likely immune
Treatment- remove any suspected initiating cause, cross matched transfusions, immunosuppressive therapy
What is aplastic anaemia and how is it treated?
Pancytopenia
Treatment- supportive, as in oestrogen toxicity, immunosupression
What is myelofibrosis?
What is it secondary too?
How is it treated?
Proliferation of collagen and reticulin fibres in bone marrow
Secondary to- chronic damage to marrow stroma, retroviral infection, idiopathic
Treatment- crossmatched transfusions, immunosupression, anabolic steroids?
What is anaemia of chronic disease?
Very common
Normocytic, normochromic non-regenerative anaemia
Mild to rarely moderate
Doesn’t require specific therapy- should resolve after chronic disease cured
What is anaemic of chronic kindey disease?
Normocytic, normochromic, non regenerative anaemia
Reduced erythropoietin production
Reduced red cell survival
Reduced erythropoiesis
Haemorrhage- thrombocytopathies, GI ulceration
How can anaemia of chronic kidney disease be treated?
Increase EPO concentrations
Minimide blood loss- gut protectants, H2 blockers
What feline retroviruses can cause non-regenerative anaemia?
FIV- erythroid dysplasia, maturation arrest
FeLV- usually non-regen, occasionally macrocytic- multiple mechanisms (red cell aplasia, aplastic anaemia, anaemia of chronic disease)
How is IDA treated?
Determine and treat underlying cause
Iron supplementation
Bloof packed red cell transfusion
How can IMHA be treated?
Complete all tests before starting therapy- immunosuppresant may mask disease
Treat underlying disease if secondary
Combination of immunesuppressive therapy, antithrombotic therapy and supportive therapy
What can be used for the immunosuppressive therapy?
Predisone- first line but side effects
Dextamethasone- may be used if oral not tolerated
Azathioprine- delayed onset 2-3weeks, can cause hepatotoxicity and myelosupression, toxic in cats
Ciclosporin- not myelosuppressive
Mycofenolate mofetil- low toxicity but expensive, GI side effects and monitoring
Leflunomide- monitoring haematology and liver tests
What are the corticosteroid side effects?
Polyuria/polydipsia/polyphagia
Muscle wastage and poor excercise tolerance
GI signs- gastritis, ulceration, pancreatitis
Long term use detrimental to many organ systems
Rationale for use of 2nd immunosupressant
When is a second immunosupressant needed for treatment of IMHA?
Clinical features of severe/life threatening disease
No response to corticosteroids over first 7d
Patient with or at risl of severe corticosteroid side effects
How can immunoglobulins be used to treat IMHA?
Human IVIG
Block fc receptors in macrophages and bind/block circulating antibodies
Salvage therapy if not responding to 2 immunosupressants
How much treatmenr should be used for IMHA and how long for?
Start high and gradually reduce doses if anaemia under control
Minimum 2-3 weeks between dose reductions
Typically for 4-8 months
Some may come off after period of months and relapse some for life
Why is antithrombotic therapyused for treatment of IMHA?
High risk of thromboembolic disease in IMHA-
severe intravascular haemolytics most at risk, anticoagulant/antiplatlet drug
What specific drugs are used for antiplatelets and anticoagulants?
Antiplatelets- clopidogrel, asprin
Anticoagulants- unfractionate heparin, dalteparine
What other supportive therapy can be used for IMHA?
Blood transfusion- base on clinical situation of patient
Gastroprotectants- omeprazole
What is neontatal isoeryhthrolysis?
Dogs:
Rare in puppies
Destruction of neonates RBCs by maternal antibody
Sensitised DEA1.1 negative bitch- positive puppies affected
Cats:
rare
Type A or AB born to type B queen
British short hair
What is microangiopathic haemolytic anaemia?
How is it caused?
RBCs are mechanically damaged or fragmented as they pass through fibrin meshworks in microvasculature
Damaged cells rapidly removed
Caused by mechanical damage:
Altered vasculature
Fibrin nets
Glomerulonephritis
Vascular anomalies/congential defects
What are schistocytes and what can cause them?
Fragmented RBCs
Caused by:
DIC
Glomerulonephritis
Neoplasia esp endothelial tumours
Vascular anomalies
What are acanthocytes and what can cause their formation?
Multiple rounded projections of variable length- unevenly spaced- on RBCs
Liver disease
Splenic HSA
Lymphoma
Glomerulonephritis
What can cause oxidative injury in dogs and cats and what does it result in?
Onions and zinc in dogs
Paracetamol in cats
Results in:
Methaemoglobinaemia
Heinz body formation
RBC membrane oxiation
RBC destroyed- tend to lyse and phagocytosed
What are heinz bodies?
What causes them?
What stain highlights them?
Round pale inclusions on inner surface of RBC membrane
Aggregated of denatured haemoglobin
New methyl blue stain highlights them
What is the treatment for oxidative damage?
Immediate withdrawl of offending cause
Supportive care
N-acetyl cysteine for paracetamol poisoining
What is intrinsic haemolytic anaemia?
Rare inherited metabolic defects
Pyruvate kinase deficiency
Phosphofructokinase deficency
Osmotic fragility
What blood parasites are their?
Babesia canis
Babesia gonis
Ehrlichia
Anaplasma
Mycoplasma haemofelis
What is mycoplasmosis?
How is it diagnosed and treated?
Mycoplasma haemofelis
Regenerative haemolysis- due to immune mediated haemolysis
May not be the primary cause of anaemia
PCR recomended- smear is hard
Doxycycline- for 21 days, cats remain carriers, flush meds
Prednisolone- ifimmune mediated component
