Haematopoietics Flashcards

1
Q

what is a bleeding disorder?

A

an abnormal condition which allows blood to escape from injured vessels or interferes with haemostasis following injury

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2
Q

in which species are bleeding disorders more common?

A

dogs > cats

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3
Q

what are the 2 stages of haemostasis?

A

primary and secondary haemostasis

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4
Q

what occurs in primary haemostasis?

A

reflex constriction of the blood vessel and formation of a platelet plug

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5
Q

what occurs in secondary haemostasis?

A

stabilisation of the platelet plug by fibrin, which results from activation of the clotting cascade

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6
Q

do primary and secondary haemostasis occur at different times?

A

no - in life, both are triggered simultaneously

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7
Q

why are vessels prone to trauma?

A

they are fragile and thin to allow transfer in and out

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8
Q

how does the vessel endothelium react to vessel injury?

A

secretes activating factors and proteins in response to a gap having formed

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9
Q

what occurs as a result of secretion of activating factors by the endothelium?

A

activates platelets, which migrate to the site of injury

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10
Q

how does vessel diameter respond to injury?

A

vasconstriction to slow blood flow to the area

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11
Q

how do platelets arrange locally at the site of injury?

A

during activation, receptors on the inside of the platelets are flipped onto the surface to make the platelets ‘stickier’ - clump at the site of injury

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12
Q

how is von Willebrands factor involved in primary haemostasis?

A

sticks to the activated proteins on the activated platelet surfaces and increases their stickiness even more

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13
Q

what is the first clot formed during primary haemostasis called?

A

primary haemostatic plug

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14
Q

what is the primary haemostatic plug?

A

the first clot formed during primary haemostasis

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15
Q

what process makes the primary haemostatic platelet plug more likely to persist?

A

vasoconstriction - helps in stopping the flow of blood down the vessel, helps protect the plug and makes it more likely that the clot will stick

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16
Q

what is von Willebrands disease?

A

deficiency of von Willebrands factor

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17
Q

what breed commonly suffers from von Willebrands disease?

A

Dobermanns

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18
Q

what is the most commonly inherited haemostatic disorder in dogs?

A

von Willebrands disease

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19
Q

what is the result of von Willebrands disease?

A

platelet adhesion/clumping impaired

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20
Q

what is the result of secondary haemostasis?

A

formation of fibrin

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21
Q

what is the purpose of fibrin?

A

scaffolds the platelets and stabilises/anchors the primary haemostatic platelet plug

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22
Q

why does secondary haemostasis occur?

A

isn’t essential for small injuries

bigger injuries require both primary and secondary haemostasis for the vessel deficit to heal

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23
Q

what are clotting factors?

A

protease enzymes which catalyse a cascade of reactions that break down proteins to make fibrin from fibrinogen

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24
Q

what are the 2 arms of the fibrin cascade?

A

intrinsic and extrinsic pathways

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25
Q

what happens to the intrinsic and extrinsic pathways of the fibrin cascade?

A

come together into a common pathway for the later stage where prothrombin is converted to thrombin

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26
Q

how is prothrombin converted to thrombin?

A

via the extrinsic and intrinsic pathways

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27
Q

what is the role of thrombin in the fibrin cascade?

A

catalyses conversion of fibrinogen into fibrin

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28
Q

what does fibrin do?

A

stabilises the primary haemostatic platelet plug

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29
Q

why can liver disease lead to coagulopathies?

A

all clotting factors are made in the liver

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30
Q

why does rodenticide poisoning lead to coagulopathy?

A

they work by binding vitamin K - required to recycle vitamin K clotting factors

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31
Q

why does rodenticide poisoning show a delayed clotting dysfunction?

A

takes a couple days for the working clotting factors in the blood to get used up before needing to be recycled by vitamin K

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32
Q

which arm of the clotting cascade is affected by vitamin K deficiency?

A

extrinsic arm

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33
Q

what type of vitamin is vitamin K?

A

fat-soluble

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34
Q

which cats may develop clotting disorders?

A

anorexic cats, cats with fat digestion issues due to blocked bile ducts (stone or pancreatitis)

(vit K is fat-soluble)

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35
Q

what are the possible defects of primary haemostasis?

A

decreased platelet number - IMTP, infectious diseases

decreased platelet function - end -stage CKD, multiple myeloma

vasculitis (adder bite)

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36
Q

what are the possible defects of secondary haemostasis?

A

quantitative disorders - decreased amount of clotting factors

qualitative disorders - decreased function of clotting factors

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37
Q

when do inherited bleeding disorders usually present?

A

<6 months

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38
Q

how can sex affect inherited bleeding disorders?

A

males are affected by sex-linked (X chromosome) coagulation disorders e..g haemophilia

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39
Q

why is it important to find out about previous trauma/surgery/toxins/drug exposure?

A

any previous trauma/surgery will usually have resulted in bleeding complications

recent toxin exposure may help to point towards the cause

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40
Q

what are primary haemostatic diseases typically characterised by?

A

multiple minor bleeds

prolonged bleeding

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41
Q

what are secondary haemostatic diseases typically characterised by?

A

single large bleeds

rebleeding

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42
Q

what are the clinical signs of primary haemostatic diseases?

A

petechiae and ecchymotic (larger) haemorrhages

often multiple sites of bleeding

prolonged bleeding from cuts/venepuncture

surface bleeding common - mms, skin, eyes

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43
Q

what are the clinical signs of secondary haemostatic diseases?

A

haematomas common

often localised site of bleeding

delayed bleeding or rebleeding from cuts

venepuncture usually uncomplicated

deep and cavity bleeds common - joints and abdominal/thoracic cavities

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44
Q

what are the considerations for blood sampling with suspected bleeding disorders?

A

collect before starting any therapy

atraumatic venepuncture to avoid excessive activation of haemostasis and local consumption of platelets

proper handling and collection of samples

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45
Q

what tests can be used for primary haemostasis testing?

A

platelet count - in-house estimation

buccal mucosal bleeding time

vWF testing (sodium citrate)

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46
Q

what is the BMBT?

A

screening test for platelet defects (number/function) and vessel wall defects

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47
Q

what is the normal BMBT?

A

<3 mins in cats
<3.5 mins in dogs

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48
Q

why is the BMBT more likely to be used to assess platelet function?

A

vessel wall disorders are rare

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49
Q

when might the BMBT test for platelet function?

A

BMBT can be prolonged in cases where the platelet count is normal but platelet function is impaired, e.g. von Willebrands disease

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50
Q

should a BMBT be carried out if thrombocytopaenia has been identified?

A

no - already know it will be prolonged

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51
Q

can a BMBT be carried out on a conscious patient?

A

can usually be done conscious in dogs

cat will require heavy sedation/GA

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52
Q

what position should the patient be in for a BMBT?

A

lateral recumbency - upper lip folded and held in place with gauze bandage tied around thr muzzle/head

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53
Q

how tight should the lip bandage be for a BMBT?

A

should mildly obstruct venous return

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54
Q

how is a BMBT carried out?

A

a pair of small standardised incisions are made in the buccal mucosa with a spring loaded bleeding time device

blood is blotted away using filter paper, WITHOUT disturbing the incision sites

time taken for cessation of bleeding is recorded

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55
Q

what can we use for identification of quantitative platelet disorders?

A

platelet counts and platelet count estimation

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56
Q

what blood tube should be used for samples intended for platelet counts?

A

EDTA

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57
Q

how can we perform an estimation of platelet count in-house?

A

examination of a stained (diff-quik) blood smear made from fresh EDTA anticoagulated blood

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58
Q

how is an estimation of platelet count performed?

A

low power - check for any platelet clumps (will influence count)

oil immersion - count platelets per field, 10 fields total

59
Q

what is represented by each platelet per high power field?

A

represents approx 20 x 10^9/l platelets in the circulation

60
Q

how many platelets in each high power field is considered normal?

A

11-25

61
Q

what does activated clotting time evaluate?

A

intrinsic and common pathways

62
Q

how does the tube for ACT measurement work?

A

contain diatomaceous earth which activates the intrinsic pathway

63
Q

why are the first few drops of blood discarded when testing ACT?

A

in case of endothelial activation factors interfering with the test results

64
Q

give a brief overview of testing for ACT

A

first few drops of blood discarded

2mls blood collected into test tube, gently invert to mix

leave undisturbed for 40 mins

tube inverted every 10 seconds and the time taken for complete clot formation is recorded

65
Q

what is evaluated by the activated partial thromboplastin time (APPT)?

A

evaluates the intrinsic and common pathways

66
Q

what is the advantage of APPT over ACT?

A

it is more sensitive than the ACT

67
Q

what is evaluated by the prothrombin time?

A

extrinsic and common pathways

PT is very sensitive to vitamin K deficiency and rodenticide toxicity

68
Q

how are the APPT and PT performed?

A

blood sampled into sodium citrate tubes and filled exactly to marked line

samples must be evaluated immediately, or double spun down to recover the citrate plasma and frozen until transported

69
Q

does APTT and PT always have to be sent away for?

A

can be done on some in-house analysers

thromboelastography starting oy be used in referral hospitals (haemostatic profile)

70
Q

why is anaemia more common in cats?

A

cats mask illness and disease - diagnosed later

lifespan of feline RBC (70 days) is shorter than dogs (110 days)

total RBC mass lower than in dogs

feline haemoglobin has low affinity for oxygen - anaemia is tolerated well

71
Q

what does it mean if feline haemoglobin has a low affinity for oxygen?

A

readily give up oxygen to tissues

72
Q

what are the clinical signs of anaemia in cats?

A

pale (or yellow) mms - most important sign

lethargy, weakness

hyperdynamic pulses

tachycardia (>200bpm)

heart murmur

tachypnoea

enlarged lymph nodes and spleen

PICA

73
Q

why do haemic murmurs occur with anaemia?

A

due to reduced viscosity of blood

74
Q

why does anaemia lead to widespread lympadenopathy and splenomegaly

A

increased removal of RBCs

75
Q

what additional signs may be seen with anaemia?

A

signs associated with the underlying cause e.g. infection with FeLV/FIV/FIP

76
Q

how might PICA present in anaemic cats?

A

owners have reported licking of concrete, eats cat litter or soil

77
Q

what is the first priority in investigation of anaemia?

A

haematological investigation - PCV

78
Q

how can a patient have a normal PCV but still have anaemia?

A

due to acute haemorrhage - volume of blood lost will reduce overall number of RBCs in direct proportion with other blood components

79
Q

why are reference ranges for PCV different for dogs and cats?

A

red blood cell density is lower in the cat than the dog

80
Q

what PCV ratio characterises chronic anaemia?

A

lower proportion of RBCs to plasma

81
Q

what PCV ratio characterises volume overload?

A

more plasma proportionally to RBCs, PCV normal

82
Q

what haematological features suggest the anaemia is regenerative?

A

reticulocytes >50x10^9/l

anisocytosis

polychromasia

MCV increased

MCHC decreased (cells less concentrated, with increased reticulocytes)

83
Q

what haematological features suggest the anaemia is non-regenerative?

A

reticulocytes <50 x 10^9/l

normocytic

normochromic

MCV normal

MCHC normal

84
Q

what is anisocytosis?

A

variation in RBC size

85
Q

what is polychromasia?

A

variation in RBC density of colour (haemoglobin)

86
Q

what does hypochromic mean?

A

pale (less haemoglobin per RBC)

87
Q

what does it mean if a RBC is nucleated?

A

earlier release from the bone marrow

88
Q

what does normocytic mean?

A

normal size

89
Q

what does microcytic mean?

A

small RBC

90
Q

what does macrocytic mean?

A

large RBC

91
Q

why is it normal to see some punctate reticulocytes in the cat?

A

because it takes longer (10d) for their RBCs to mature

92
Q

what type of reticulocytes can develop in the cat?

A

aggregate and punctate

93
Q

what type of reticulocyte do dogs have?

A

aggregate

94
Q

what type of reticulocytes represent active bone marrow regeneration in cats?

A

aggregate - rarely seen in normal cats, unlike punctate

95
Q

what does the presence of aggregate reticulocytes mean in cats?

A

active bone marrow regeneration - regenerative anaemia

96
Q

what stain is required for reticulocyte counts?

A

new methylene blue

97
Q

what is the best way to establish whether an anaemia is regenerative or not??

A

performing an absolute reticulocyte count

98
Q

how do we determine the absolute reticulocyte count?

A

absolute reticulocyte count (x10^9/l) =

observed % reticulocytes / RBC count (x10^12/l) x 10

99
Q

why is it important to determine whether an anaemia is regenerative or not?

A

important for differential diagnoses - regenerative anaemias arise only due to blood loss or haemolysis

100
Q

what are the main confounding factors which make it more difficult to categorise anaemia?

A

duration of anaemia

concurrent disease

101
Q

why is duration of anaemia a confounding factor in categorising anaemia?

A

regenerative - takes 2-5 days for retics to be released from bone marrow and appear in circulation, in this time will appear to be non-regenerative

102
Q

how can anaemia be affected by speed of blood loss?

A

slow bleeding e.g. chronic GI blood loss

eventually leads to iron deficiency anaemia, which impairs erythropoiesis - started off as regenerative but, with time, becomes non- or poorly regenerative anaemia

103
Q

are cats commonly affected by iron deficiency anaemia?

A

relatively rare except in kittens with chronic flea infestation

104
Q

how is concurrent disease a confounding factor in categorising anaemia?

A

many chronic diseases (inc FeLV), both infectious and inflammatory, can reduce bone marrow response to anaemia, making regenerative causes of anaemia appear non-regenerative

105
Q

what are the main causes of haemorrhage causing regenerative anaemia?

A

trauma

coagulopathies

chronic blood loss from flea infestations, infected tumours, GI tract

106
Q

what type of anaemia results from chronic blood loss from flea infestations/infected tumours/GI tract?

A

non-regenerative microcytic hypochromic iron deficiency anaemia

(due to depleted iron reserves)

107
Q

what are the different potential causes of regenerative anaemia due to haemolysis?

A

infectious - FeLV and FIA

immune-mediated - drugs, neoplasia, FeLV

Heinz body anaemia

severe hypophosphataemia (refeeding syndrome)

incompatible blood transfusions

neonatal isoerythrolysis

inherited defects (rare)

108
Q

which findings may suggest an underlying haemolytic anaemia?

A

pre-hepatic jaundice (uncommon)

haemoglobinuria (uncommon)

lymphadenopathy/splenomegaly as a result on increased RBC destruction

109
Q

is immune mediated haemolytic anaemia common in cats?

A

less common as a primary condition (unlike in dogs) - seen secondary to drugs (e.g. methimazole), some cancers, FIA

110
Q

what do Heinz bodies represent?

A

irreversibly denatured oxidised haemoglobin

111
Q

are Heinz bodies a normal finding in cats?

A

<5% RBCs with Heinz bodies can be normal

112
Q

why might Heinz body anaemia occur in a cat?

A

oxidative damage caused by:

paracetamol toxicity

onion toxicity

lymphoma

DKA

113
Q

how do incompatible blood transfusions cause haemolysis of RBCs?

A

antibodies in donor/recipient plasma attack naturally occurring antigens on the RBCs

114
Q

how does neonatal isoerythrolysis occur?

A

occurs when kittens nurse and drink milk high in anti-A antibodies

A kittens born to B queens

115
Q

how can neonatal isoerythrolysis be avoided?

A

screen queens and toms - only breed B toms with B queens

116
Q

which breeds are more likely to be affected by neonatal isoerythrolysis?

A

brachy breeds - persians, birmans, british shorthairs

117
Q

what causes feline infectious anaemia?

A

Mycoplasma haemofelis

118
Q

how is Mycoplasma haemofelis trasmitted?

A

fleas

119
Q

what are the signs of feline infectious anaemia?

A

pallor
lethargy
anorexia
weight loss
pyrexia
dehydration

jaundice if severe acute disease

120
Q

how can feline infectious anaemia be diganosed?

A

PCR of blood - 0.5ml EDTA required

121
Q

how is feline infectious anaemia treated?

A

doxycycline antibiotic followed by food/syringed water - risk of oesophagitis if stays in oesophagus

122
Q

what type of anaemia is a cat most likely to have?

A

most common is non-regenerative

123
Q

what is a non-regenerative anaemia?

A

where the bone marrow fails to respond adequately to the anaemia, and does not produce adequate new RBCs

124
Q

why might a non-regenerative anaemia occur?

A

can arise due to disorders of the bone marrow itself OR suppression of normal bone marrow response due to systemic disease

125
Q

what is required to diagnose non-regenerative anaemia when severe?

A

bone marrow sampling

126
Q

where is bone marrow sampling carried out in cats?

A

humerus or femur (under GA)

127
Q

what conditions might cause a secondary non-regenerative anaemia?

A

neoplasia
FeLV/FIV/FIP
bacterial infections
CKD
chronic inflammation

128
Q

how does chronic inflammation induce anaemia?

A

may induce a mild-moderate non-regenerative anaemia, partly due to marrow suppressive effects of circulating toxins, but also due to sequestration of iron reserves

129
Q

how severely can anaemia due to inflammatory disease develop?

A

very common but rarely severe

130
Q

how does CKD induce anaemia?

A

variety of mechanisms:
reduced RBC lifespan
blood loss
impaired iron utilisation
EPO deficiency

131
Q

where/when is erythropoietin produced?

A

produced by the kidneys in response to hypoxia

132
Q

what is the effect of erythropoietin?

A

stimulates RBC production in the bone marrow

133
Q

when might a blood transfusion be required in an anaemic cat?

A

often critical on presentation - may be necessary as a life-saving measure

134
Q

when might a blood transfusion be used as an adjunct treatment?

A

cases with FIA and non-regenerative anaemias, or whilst awaiting response to specific therapy or results of diagnostic investigations

135
Q

what is the decision around blood transfusion based on?

A

clinical grounds, rather than a particular PCV cut-off

generally if PCV >10% transfusion will be unnecessary in chronically anaemic cats

136
Q

why is transfusion unnecessary in chronically anaemic cats with PCV >10%?

A

due to compensatory mechanisms the cat develops with chronic anaemia - acute patients will be affected much more severely than those with gradual development

137
Q

in which cats might erythropoietin therapy be useful?

A

those with anaemia secondary to CKD

138
Q

what are the disadvantages of using erythropoietin to treat anaemia?

A

not all patients respond and there are a number of side effects
not licensed - must be used under cascade

139
Q

how might we reduce side effects of erythropoietin treatment?

A

use of newer recombinant human erythropoietin

140
Q

which treatment for anaemia is available in a primary care setting?

A

anabolic steroids e.g. laurabolin

141
Q

why is anaemia often treated empirically?

A

in significant proportion of cases of marrow failure, no underlying cause can be determined

142
Q

how do anabolic steroids help treat anaemia?

A

may stimulate erythroid precursors in bone marrow, via an effect on EPO activation

little convincing evidence of any convincing effect

143
Q

when might prednisolone therapy be used for anaemia?

A

considered as treatment on the basis that an immune-mediated mechanism has been proposed in some cases of marrow failure

144
Q
A