Regenerative anaemias Flashcards

(54 cards)

1
Q

Causes of acute haemorrhage

A

Trauma
Bleeding tumours
Coagulopathies
Severe thrombocytopaenia

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2
Q

Signs of acute haemorrhage

A

Collapse
Tachycardia with weak pulses
Pallor
Hypovolaemic shock

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3
Q

What happens immediately after acute haemorrhage?

A

PCV and plasma protein will be unchanged (as equal volumes lost)

Splenic contration - releases more red cells, compensating for red cell loss

Fluid moves from interstitium into vessels, dilutes the remaining red cells and platelets

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4
Q

What happens after acute internal haemorrhage?

A

Most erythrocytes will be reabsorbed

Plasma proteins are rapidly reabsorbed

Acute phase response leading to production of globulins, thus plasma protein concentrations normalise quickly

Around 65% of red cells will be reabsorbed within 2-3 days and 80% will return to the circulation within 2 weeks.

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5
Q

What happens after acute external haemorrhage?

A

Marked regenerative response

Plasma protein will normalise more quickly then PCV

May also have a mild-moderate thrombocytopaenia

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6
Q

Chronic haemorrhage

A

Often associated with GI bleeding (may see melaena or haematochezia), sometimes urinary tract

Body is able to adapt to reduced oxygen carrying capacity

Signs usually mild

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7
Q

How to check for GI bleeding

A

Faecal occult blood test

may need to feed white meat for 3 days prior as myoglobin from red meat can be registered

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8
Q

What to do if you suspect chronic haemorrhage (low PCV, or low normal and low iron), but there is no obvious cause?

A

Urinalysis, dipstick and sediment

Feacal analysis (for ectoparasites and faecal occult blood)

Abdominal ultrasound examination/contrast radiography of the GI tract or urinary tract

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9
Q

Hypochromasia

A

red cells have a larger area of central pallor.

Usually this is secondary to iron deficiency.

Reticulocytes are also hypochromatic although they have grey-blue colouration.

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10
Q

Differences between haemolytic and haemorrhagic anaemias

A

Haemolytic: plasma protein normal or increased (usually decreased in haemorrhage)

Haemolytic tend to be more regenerative as not losing iron (unless damage to precursor cells in bone marrow)

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11
Q

Extravacsular haemolysis

A

Occurs when erythrocytes are phagocytosed by macrophages in the spleen and liver

Often associated with splenomegaly and spherocytes

Insidious onset

Mild to severe anaemia

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12
Q

Intravascular haemolysis

A

Erythrocytes are lysed within blood vessels

Usually due to red cell membrane damage -> ghost cells

often rapid onset, severe anaemias

Poor prognosis

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13
Q

Clinical signs of intravascular haemolytic anaemia

A

Haemoglobinaemia
Haemoglobinuria

May have
Hyperbilirubinaemia
Bilirubinuria

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14
Q

Signs of extravascular haemolytic anaemia

A

Hyperbilirubinaemia
Bilirubinuria
Splenomegaly

Haemoglobin is broken down to bilirubin by macrophages so dont see haemoglobinaemia/uria

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15
Q

Causes of haemolytic anaemias

A

Immune mediated
- Primary: idiopathic
- Secondary: drugs, vaccines, infectious agents, alloimmune, neoplasia

Bacteria, protozoal, viral infection

Oxidative damage

Disorders causing erythrocyte fragmentation

Inherited erythrocyte metabolic disorders

Severe hypophosphataemia

Evenomation

Haemophagocytic histiocytic sarcome

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16
Q

IMHA - general info

A

Dogs: common, usually primary (idiopathic), females overrepresented, Cocker spaniel, English Springer spaniel, poodles, Irish setter

Cats: less common, more often secondary

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17
Q

What can IMHA be secondary to?

A

Drugs (e.g. potentiated sulphonamides, cephalosporins, NSAIDs)

Vaccination? (controversial).

Infections; e.g.
o Dogs – Babesia, Anaplasma, Ehrlichia, leishmania.
o Cats – FeLV, Mycoplasma.

Neoplasia (especially lymphoproliferative diseases)

Following improperly cross matched transfusions

Neonatal isoerythrolysis

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18
Q

What is Evans syndrome?

A

IMHA and IMTP seen together

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19
Q

Pathophysiology of IMHA

A

Immune system produces antibodies directed against the surface of red cells most often IgG, but sometimes IgM.

Recognised by macrophages

Macrophages either destroy whole RBC or remove part of membrane to give spherocytes

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20
Q

What are spherocytes?

A

Small round densely staining red cells, which lack central pallor.

RBC membrane has been partially phagocytosed by macrophage, leaving less membrane to maintain the biconcave discoid shape, therefore the cells become spheroid in shape. They are difficult to see in species other than dogs due to the lack of central pallor in normal cells from other species (i.e. cat). Low numbers can also be seen in normal blood smears, especially at the tail of the smear (artefact).

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21
Q

Differentials for spherocytosis

A

IMHA (if >20 per hpf)
PFK deficiency
Zinc toxicity
Evenomation

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22
Q

Clinical signs of IMHA

A

Acute severe anaemia or more insidious, less severe anaemia

Lethargy, pallor, weakness, exercise intolerance, tachycardia

Pyrexia

Jaundice (hyperbilirubinaemia, bilirubinuria)

Haemoglobinaemia and consequent haemoglobinuria

Splenomegaly and hepatomegaly if extravascular

+/- lymphadenopathy (mild)

Tachypnoea

23
Q

Diagnostic features suggestive of IMHA

A

Regenerative anaemia (moderate to severe)

Bilirubinuria/haemoglobinuria

Hyperbilirubinaemia/ haemoglobinaemia

Spherocytosis (in dogs)

Ghost cells

Marked anisocytosis and increase in RDW due to the presence of large reticulocytes and small spherocytes

Neutrophilia (may be marked)

Liver enzymes may be elevated due to hypoxic damage

24
Q

Definitive diagnosis of IMHA

A

Autoagglutination
- grossly in tube or in saline agglutination test (SAT)
- can be non-specific, if unsure wash and retest
- only moderately sensitive

Coombs test
- serial dilurtions of Coombs reagent with washed RBCs from patient
- if IMHA present will cause autoagglutination
- diagnostic

25
Rouleaux
Appreciated visually as the cells clustering to look like a stack of coins. It is very common in normal cats and horses, and can be associated with hyperglobulinaemia. It can be differentiated from agglutination of cells by performing an in saline agglutination test (Rouleaux will disperse, agglutination will remain).
26
Further diagnostics to consider if IMHA is diagnosed (to look for secondary causes)
Imaging to look for neoplasia Rule out drug exposure from history PCR/serology for infectious agents - Babesia canis - Mycoplasma (cats) - FeLV (cats) Bone marrow examination - if anaemia is non-regenerative which could suggest precursor targeted immune mediated anaemia (PIMA)
27
Common infectious causes of haemolytic anaemias (not IMHA)
Haemotropic mycoplasmas (cats Babesia (dogs, cattle) FeLV (cats) Leptospirosis (cattle, lambs, pigs) Clostridium (ruminants, horses) Equine infectious anaemia (horses)
28
Haemotropic mycoplasmas
AKA Feline infectious anaemia Mycoplasma haemofelis most pathogenic Transmission unknown - fleas, fighting? Attach to red cell membrane causing distorsion and extravascular haemolysis - some can cause antibody response leading to IMHA Cycline lasting 1-2d with 6d intervals, some become chronically infected carriers Can be seen in immune compromised dogs
29
Diagnosis of haemotropic mycoplasmas
Mycoplasmas can be seen on the blood smear but sensitivity is low Appear as small coccoid organisms on edge or within cells, sometimes forming chains - care not to confuse with stain precipitate PCR of blood most sensitive
30
Treatment of Haemotropic mycoplasma
Doxycycline Immunosuppression may be indicated in IMHA suspected
31
Babesiosis
Intracellular protozoan parasites that are spread by the Dermacentor species of tick Usually only in dogs that have travelled but sporadic cases that have not Babesia can also affect cattle (red water fever) and it is spread between cattle by the Ixodes Ricinus tick. Can cause extravascular or intravascular haemolysis (+/- IMHA)
32
Diagnosis of Babesia
Can see on as paired intracytoplasmic organisms on blood smear (particularly red cells just below buffy coat) ○ More likely seen from capillary blood (e.g. ear prick) PCR – most sensitive Serology – shows exposure
33
Treatment of Babesia
Imidocarb diproprionate
34
Blood groups in dogs
Generally it is ok to transfuse a dog once without blood typing or cross matching (provided not given birth or been previously transfused). Many blood groups are described in dogs, but the most clinically relevant is DEA 1.1. Natural alloantibodies against DEA 1.1 are not present in dogs but are induced following transfusion or pregnancy/parturition. DEA 1.1 negative dogs will develop alloantibodies if transfused with DEA 1.1 positive blood and DEA 1.1 negative bitches that birth a DEA 1.1 positive pup will also develop anti-DEA 1.1 antibodies (if exposed to blood during parturition).
35
Blood groups in cats
Must blood type +/- cross match before transfusion. Three blood groups are described; group A (most common in Domestic Short Haired cats), group B (more common in British shorthair, Birman, Devon Rex, Cornish Rex), and group AB (least common). Cats have naturally occurring alloantibodies: * A type cats have weak anti-B alloantibodies (-> minimal transfusion reaction). * B type cats have strong anti-A alloantibodies (-> strong transfusion reaction). * AB type cats have no naturally occurring alloantibodies
36
Blood groups in horses
Horses have a complicated system of blood typing but groups Aa, Ac, Ca, Qa are the most clinically relevant. Horses that lack Aa, Ac, Ca antigens may have natural anti-Aa/Ac/Ca alloantibodies. In addition, Qa negative mares may develop anti Qa antibodies after birthing a Qa positive foal. Many thoroughbreds are Aa or Qa positive.
37
Neonatal isoerythrolysis in cats
Occurs in type A kittens born to a type B mother. Anti-A antibodies will be present in colostrum and so will be absorbed into blood stream of kitten leading to haemolytic anaemia. These antibodies will cause intravascular haemolysis, severe anaemia, and sudden death. This can be avoided by blood typing mothers and toms to avoid a type A tom breeding with a type B queen. Otherwise type A kittens can be kept away from the type B mother for the first 48 hours after birth to avoid colostrum intake and allow gut closure to occur.
38
Neonatal isoerythrolysis in horses
This will occur in Aa or Qa negative mares that acquires natural anti-Aa/Qa alloantibodies during previous foaling or transfusion and that give birth to a Aa/Qa positive foal.
39
Transfusion reactions in cats
Will see strong reaction if type A blood is given to a type B cat. Less severe reaction if type B blood given to type A cat, however blood typing or cross matching should be performed in all cases prior to transfusion.
40
Transfusion reactions in dogs
No naturally occurring DEA 1.1. alloantibodies, so dogs can be transfused safely once, without cross matching/blood typing, provided they have not been transfused before, or been pregnant/given birth.
41
Haemolytic anaemias due to oxidative injury
Oxygen within red cells is a potent oxidant which can cause formation of reactive oxygen species that can damage cells. Oxidant damage is limited by the presence of protective enzymes within red cells, however oxidative toxins can overwhelm action of protective enzymes leading to oxidative injury. Oxidation of red cells can cause damage in a number of ways: * Oxidation of globin chains leading to Heinz body formation * Cell membrane damage leading to eccentrocyte formation * Oxidation of Fe2+ in haem molecule to Fe3+ leading to methaemoglobin formation
42
Heinz bodies
These form due to oxidation of the SH groups in the globin chain. The Heinz body is precipitate of Hb attached to the inside of the red cell membrane. Affected cells are less deformable and so are phagocytosed in the spleen (extravascular haemolysis) or severely damaged cells are haemolysed in the circulation (intravascular haemolysis). Heinz body formation is more common in cats due to an increased number of SH groups (8 vs 4 in dogs). Heinz bodies can be seen on normal blood smears, where they appear as an unstained projection on the cell membrane, or can be seen more easily following staining of the cells with new methylene blue (Heinz bodies stain blue).
43
Causes of Heinz body anaemias
* Onion * Garlic (dogs) * Paracetamol (dogs and cats) * Zinc (dogs) * Red maple leaves (horses) * Kale and rape (ruminants)
44
Direct membrane damage (due to oxidative injury)
Zinc and napthalene (moth balls) cause membrane damage and intravascular haemolysis with minimal or absent Heinz body / MetHb formation. Membrane damage results in formation of eccentrocytes – red cells in which haemoglobin is displaced to one side of the cell leaving a pale empty area on the other side. Again these are less deformable and so are removed by the spleen leading to extravascular haemolysis.
45
Oxidation of the haem molecule (causing haemolytic anaemia)
Fe2+ is oxidised to Fe3+, resulting in the formation of methaemoglobin (MetHb). Blood appears chocolate brown when 30 – 40% of total haemoglobin is in the form of methaemoglobin, and death occurs when it reaches 80 – 90%. You can test for MetHb by dropping venous blood onto white blotting paper. MetHb blood will remain brown, whereas normal blood will turn bright red (due to formation of oxyhaemoglobin).
46
Paracetamol toxicity
Methaemoglobinaemia - causing choclate brown blood Cats are very sensitive to paracetamol because lack specific glucuronyl transferases required to conjugate aromatic compounds. Toxic dose usually 50 – 60 mg/kg, although fatal intoxication with total dose of 125 mg (1/4 tablet) has been reported. The toxic dose of paracetamol for dogs is much higher (150 – 200 mg/kg).
47
Clinical signs of paracetamol toxicity
* Acute intravascular haemolysis -> haemoglobinuria (urine may be deep brown). * +/- Jaundice * Facial oedema * Salivation * Depression * Dilated unresponsive pupils * Vomiting * Tachycardia and moist rales * Seizures
48
Treatment of paracetamol toxicity
N-acetylcysteine - this drug increases sulphate availability for conjugation of paracetamol and also provides cysteine for glutathione regeneration. Fluid therapy to avoid renal tubular damage due to haemoglobinaemia
49
How can erythrocytes be damaged?
Abnormal vessels e.g. vascular tumours/haemangiosarcoma Fibrin clots e.g. in disseminated intravascular coagulation (DIC) Valvular disease (endocarditis)
50
What is seen on the blood smear of an animal that has a disorder associated with erythrocyte fragmentation
Acanthocytes - rounded, variable sized projections. Can be seen in normal dogs but also disorders causing fragmentation and liver disease Schistocytes - fragment sof RBCs, so should be smaller than single RBC Differentiate from crenated cells which are usually artefactual
51
Inherited erythrocyte metabolic disorders
Inherent metabolic defects - red cell enzyme deficiencies Leads to membrane damage and accelerated extravascular haemolysis and anaemia Red cell pyruvate kinase (PK) deficiency in Basenjis Red cell phophofructokinase (PFK) deficiencies in ESS, and Cockers.
52
Red cell pyruvate kinase (PK) deficiency
Occurs in Basenjis as well as other breeds of dogs and some breeds of cats. Associated with a highly regenerative, severe anaemia, and often has a poor prognosis due to the development of myelofibrosis in middle age.
53
Red cell phosphofructokinase (PFK) deficiency
Reported in English Springer spaniels and Cocker spaniel. Mild or no anaemia, but haemolytic crisis may occur following exercise when hyperventilation leads to alkalemia. The red cells show a markedly alkaline fragility and so there is an increased rate of haemolysis during alkalemia.
54
Hypophosphataemia and anaemia
Low phosphate availability leads to ATP depletion which in turn increases RBC membrane rigidity and decreases deformability of the cells, leading to intravascular haemolysis. This can occur in small animals following insulin therapy for diabetes mellitus (since insulin causes phosphate to move into cells) or can occur in post parturient hypophosphataemia in cattle (3-8 weeks post-partum).