4.3.5: Haemostatic disorders - Bleeding disorders

Question 1

Clinical signs of primary haemostatic disorders

Answer 1

• Petechiae/ecchymoses are common
• Bleeding from mucus membranes
• Often more than one site of bleeding
• Prolonged bleeding at sites of injury

Question 2

Clinical signs of secondary haemostatic disorders

Answer 2

• Petechiae/ecchymoses are rare
• Deep or cavity bleeds; can bleed from mucus membranes
• Sometimes single site of bleeding

Question 3

A puppy comes in bleeding from the mouth where its new teeth are coming through. What type of haemostatic disorder are you suspicious of?

Answer 3

Primary haemostatic disorder (bleeding from mm common)

Question 4

Compare the clinical signs of primary vs secondary haemostatic disorders

THIS IS IMPORTANT

Answer 4

Question 5

Answer 5

Hyphaema

Bleeding into the anterior chamber of the eye

Question 6

Answer 6

Haematoma after jugular sample. This dog had rodenticide toxicity.

Question 7

Answer 7

Petechiae
Small pinprick haemorrhages
Tiny vessels bleed into the skin and mucus membranes

Question 8

Answer 8

Ecchymoses
Haemorrhage under the skin.
5p coin size or bigger.

Question 9

If you need to take blood from an animal but you are suspicious of a coagulopathy, what should you do?

Answer 9

Take blood from a leg (not jugular), put on a pressure bandage afterwards, and watch carefully.

Question 10

Name of this test and how it helps us differentiate between petechiae and allergies

Answer 10

Diascopy
* Microscope slide is pressed against the lesion to see if it blanches
* If it blanches (positive result) = erythema secondary to vasodilation. e.g. allergies
* If it does not blanche (negative result) = bleeding into the skin e.g. petechiae

Question 11

What named factor is involved in primary haemostasis and what does it do?

Answer 11

Von Willebrand Factor
Acts as the “glue” sticking platelets to each other and to the subendothelial matrix on a damaged vessel

Question 12

Broad causes of primary haemostatic disorders

Answer 12

• Thrombocytopaenia
• Thrombocytopathia
• vWF deficiency

Question 13

What tests can you do to diagnose a primary haemostatic disorder?

THIS IS IMPORTANT

Answer 13

• Platelet count
• Buccal mucosal bleeding time
• vWF antigen test
• Platelet function assays

Question 14

Causes of thrombocytopaenia

Answer 14

1. Defective platelet production
2. Accelerated platelet removal
3. Platelet sequestration or loss

Question 15

Examples of diseases that could cause defective platelet production and therefore thrombocytopaenia

Answer 15

• Bone marrow neoplasia e.g. leukaemia
• Drug/chemical/toxin-induced bone marrow suppression
• Bone marrow infections esp. viral and rickettsial

Question 16

Examples of diseases that could cause accelerated platelet removal and therefore thrombocytopaenia

Answer 16

• Immune-mediated thrombocytopaenia (IMTP) –> most common!
• Consumption in microangiopathic conditions e.g. DIC

Question 17

Examples of diseases that could cause platelet sequestration or loss and therefore thrombocytopaenia

Answer 17

• Splenomegaly/vascular pooling
• Acute ongoing haemorrhage

Question 18

What type of anaemia is observed here? How do we know this?

Answer 18

Regenerative anaemia
There are spherocytes and reticulocytes visible

Question 19

How can IMTP be categorised?

Answer 19

Immune mediated thrombocytopaenia
* Primary = idiopathic
* Secondary = drug-induced/secondary to infection or neoplasia

Question 20

IMTP signalment

Answer 20

• Young to middle aged, female dogs are over-represented
• Breeds: Cocker Spaniels, miniature/toy poodles, Old English sheepdogs

Question 21

IMTP treatment

Answer 21

• Treat any underlying disease
• Whole blood transfusion can be justified if life-threatening bleeding, but it typically doesn’t significantly raise platelet count
• Long-term treatment centres around immunosuppression
• Splenectomy has had variable results but could be considered in refractive cases
• Patient will require ongoing monitoring

Question 22

IMTP prognosis

Answer 22

• Can be good: 10-15% mortality, 10-40% relapse
• Negative prognostic indicators: melaena, high BUN

Question 23

Thrombocytopathia

Answer 23

any kind of abnormal platelet function.
* Can be congenital or acquired.
* Clinical signs similar to thrombocytopenia, but platelet count is normal

Question 24

Causes of thrombocytopathia

Answer 24

• Inherited thrombopathias
• Drug induced defects of platelet function e.g. several drugs including NSAIDs
• Platelet dysplasia (=neoplasia)

Question 25

Diagnosis of thrombopathia

Answer 25

* Normal platelet counts but prolonged BMBT * Normal levels of vWF * Platelet function tests/assays To a certain degree it is often a diagnosis of exclusion.

Question 26

Thrombopathia treatment

Answer 26

* No specific therapy * Platelet transfusions are not possible * Withdraw any drugs e.g. NSAIDs * Treat symptomatically e.g. blood transfusions if marked anaemia

Question 27

**von Willebrand's Disease (vWD)**

Answer 27

* Most common inherited bleeding disorder in dogs * Affects wide range of dog breeds; rare in cats * Can be classified as Type I, II and III

Question 28

Clinical signs of vWD

Answer 28

* Typical of a primary haemostatic defect: mucosal haemorrhage, cutaneous bruising, prolonged bleeding from wounds * Occasionally more profound bleeding occurs: * Epistaxis * Haematuria * GI haemorrhage * Prolonged oestral bleeding * Gingival bleeding at tooth eruption reported

Question 29

Diagnosis of vWD

Answer 29

* Platelet count is normal (check first using a blood smear) * BMBT is a useful screening test (severe forms of vWD >12 min) * vWF antigen test * Genetic testing is available: can classify as clear/carrier/affected

Question 30

Treatment of vWD

Answer 30

* Plasma transfusion - in severe cases * Cryoprecipitate * Transfuse red cells (if oxygen carrying capacity compromised) * Type I: desmopressin to stimulate release of vWF from endothelial cells. Will not work in Type II and III.

Question 31

Example of breed prone to vWD

Answer 31

Dobermann

Question 32

**Primary haemostasis**

Answer 32

formation of a platelet plug. When a vessel is injured, platelets adhere to collagen; vWF is needed for this. * Involves platelets, endothelial cells, vWF, thrombin, collagen

Question 33

**Secondary haemostasis**

Answer 33

=formation of a fibrin clot under the influence of clotting factors specifically thrombin; stabilisation of the platelet plug. * Involves fibroblasts, platelets, endothelial cells, leukocytes * Involves Factors II, VII, IX, X, XI * Also involves non-enzymatic coagulation factors e.g. tissue factor, Factor V and VIII

Question 34

1

Answer 34

aPTT

Question 35

2

Answer 35

ACT

Question 36

3

Answer 36

PT

Question 37

Which factor has the shortest half-life and so will disappear first?

Answer 37

Factor VII

Question 38

If your patient has a very high PT, but APTT is not so high, what are you suspicious of?

Answer 38

This patient has eaten rat poison until proven otherwise * This occurs because Factor VII (shortest half life) has disappeared first * This is part of the extrinsic and common pathway, which PT tests * aPTT tests the intrinsic and common pathways; the intrinsic pathway does not involve Factor VII, hence the aPTT result is not very high yet

Question 39

If fibrinogen is low, what does this suggest?

Answer 39

The patient is making a lot of clots and has used it all up

Question 40

Factor 1 is also known as

Answer 40

fibrinogen

Question 41

What is fibrinogen? Where is it made and how? Why might it be high/low?

Answer 41

**Fibrinogen:** a.k.a. Factor 1, the final factor into the coagulation cascade. It is a soluble plasma glycoprotein synthesised by the liver. * Fibrinogen is converted by thrombin into fibrin during blood coagulation * Fibrinogen will be elevated in any form of inflammation (it is an acute phase protein) -> this elevation takes 24-48hrs and often occurs before other clinical signs * Low levels of fibrinogen = systemic activation of the clotting system has occured and there has been consumption of clotting factors

Question 42

What is produced from the breakdown of fibrinogen?

Answer 42

FDPs are produced from the breakdown of fibrinogen Their presence indicates a pro-thrombotic state

Question 43

Why might fibrinogen be increased?

Answer 43

* Elevated in inflammation * Indication of DIC * Potential bleeding/ making lots of clots

Question 44

Why might fibrinogen be decreased?

Answer 44

* Viral and bacterial infection * Kidney disease * Traumatic injuries, surgery * Cancer * Heart disease * Canine pregnancy, post-abortion * DIC (due to consumption) * Liver failure

Question 45

How does rodenticide toxicity impact the coagulation cascade?

Answer 45

* Vitamin K is an essential cofactor to the function of Factor II, VII, IX, and X * If there is low Vitamin K, fibrin formation is defective (i.e. rodenticide toxicity = rubbish secondary haemostasis) * Warfarin and rodenticides cause relative vitamin K deficiency because they inhibit Vitamin K reductase which is needed for recycling of Vitamin K to its active form

Question 46

Clinical signs of rodenticide toxicity

Answer 46

* Clinical signs mimic coagulation factor deficiencies * Spontaneous haemorrhage into body cavities * SC haematomas * Prolonged bleeding from wounds

Question 47

Clinical signs of failure of secondary haemostasis

Answer 47

* Deep or cavity bleeds * Mucus membranes may bleeding * Sometimes single site of bleeding * Haematomas are common ## Footnote Petechiae / ecchymoses are rare in secondary haemostasis

Question 48

Diseases of secondary haemostasis

Answer 48

* Congenital: haemophilia * Acquired: Vitamin K antagonism (coumarin/ rodenticide toxicity), hepatic disease

Question 49

Tests of secondary haemostasis ## Footnote THIS IS IMPORTANT

Answer 49

* **Activated clotting time (ACT)** : modification of APTT, assess intrinsic and common pathways. Less sensitive, good screening test. * **Prothrombin time (PT)**: a.k.a. OSPT, measures extrinsic and common pathways. * **Activated partial thromboplastin test (APTT)**: useful screen for intrinsic and common pathways. * **Thrombin clot time (TCT)** : direct measure of the function of fibrinogen. * **Fibrinogen** is converted into fibrin during coagulation. * **Whole blood clotting time (WBCT)** * **Specific factor assays**

Question 50

What does ACT measure?

Answer 50

**ACT: activated coagulation time** * Modification of APTT * Tests intrinsic and common pathways * Requires patient platelets and calcium * Less sensitive than APTT * Good quick in-house screening test

Question 51

What does prothrombin time measure and what are the normal intervals for dogs and cats?

Answer 51

**Prothrombin time (PT)** * Measures activity of extrinsic and common pathway factors * Prolonged time = due to a deficiency of any one factor * Normal dog = 7-10s * Normal cat = 7-10s

Question 52

What does APTT measure and what are the normal intervals for dogs and cats?

Answer 52

**Activated partial thromboplastin time** * Useful screen for intrinsic and common pathways * Prolonged due to a deficiency of any single factor * Intervals depend on machine used * Normal dog = 12-20s * Normal cat = 12-22s

Question 53

What does TCT and what does an abnormal result indicate?

Answer 53

**Thrombin clot time** * Direct measure of the function of fibrinogen * Prolonged TCT indicates decreased clot formation and will occur if there is a deficiency in/ abnormal fibrinogen

Question 54

What does WBCT measure and what are the normal intervals?

Answer 54

**Whole blood clotting time (WBCT)** * Crude measure of the intrinsic and common pathways * Will also be increased if thrombocytopaenia is present * Normal dog = 3-13 mins * Normal cat = 8 mins

Question 55

What do specific factor assays measure and when would you use them?

Answer 55

**Specific factor assays** * Measure the level of some individual clotting factors * Used in the investigation of inherited coagulation disorders

Question 56

What are the two forms of haemophilia and how will you diagnose them?

Answer 56

**Haemophilia A** * Sex-linked inherited, affects males * Patient suffer spontaneous, life-threatening bleeding episodes * Deficiency of Factor VIII (essential to intrinsic pathway) * Results in prolonged APTT * Confirm with specific Factor VIII assay **Haemophilia B** * Sex-linked inherited * Deficiency of Factor IX * Clinically identical to Factor VIII deficieny as both at same point in pathway * Confirm with specific Factor IX assay

Question 57

Treatment of haemophilia

Answer 57

* Pain relief (care with drugs) * Restrict movement * Fresh plasma/ FFP/ whole blood can be considered for serious bleeding * Often animal will experience small bleeds which are contained by anatomical structures e.g. haemarthrosis

Question 58

How long does it take rodenticide toxicity to have an effect?

Answer 58

1-2 days Can take as long as 1 week

Question 59

Diagnosis of rodenticide toxicity

Answer 59

Initially PT/ OSPT is prolonged Later APTT also increases

Question 60

Treatment of rodenticide toxicity

Answer 60

* Decontamination of the GIT esp if consumption in last few hours: emesis, gastric lavage, enema, activated charcoal etc. * Specific therapy: **Vitamin K** (injectable or oral) for weeks to months * PT promptly returns to normal with treatment but will increase if treatment withdrawn too early

Question 61

**True/false:** advanced liver disease is a major differential that should be ruled out in cases of suspected coagulopathies.

Answer 61

**True** * Many clotting factors and their inhibitors are synthesised in the liver * Vitamin K dependent factors are also activated in the liver * In cases of coagulopathy due to liver disease, there is elevation of both PT and APTT * **In liver disease, factors go down, and coagulation times go up.**

Question 62

**True/false:** if you suspect advanced liver disease, taking a biopsy is a good first step to confirm your suspicions.

Answer 62

**False** * They may bleed from the biopsy * Test liver enzymes and coags first before you make the patient bleed out

Question 63

What are some good general principles for management of a patient with either a pimary or secondary coagulopathy?

Answer 63

* Avoid injections, but if you have to, go for SC over IM * Vitamin K is like injecting oil, so supplement orally within 7 days of toxicity if you can * Minimise invasive procedures * Handle gently - they will bleed. Sedate if required to avoid further trauma.