4.3.5: Haemostatic disorders - Bleeding disorders Flashcards
Clinical signs of primary haemostatic disorders
- Petechiae/ecchymoses are common
- Bleeding from mucus membranes
- Often more than one site of bleeding
- Prolonged bleeding at sites of injury
Clinical signs of secondary haemostatic disorders
- Petechiae/ecchymoses are rare
- Deep or cavity bleeds; can bleed from mucus membranes
- Sometimes single site of bleeding
A puppy comes in bleeding from the mouth where its new teeth are coming through. What type of haemostatic disorder are you suspicious of?
Primary haemostatic disorder (bleeding from mm common)
Compare the clinical signs of primary vs secondary haemostatic disorders
THIS IS IMPORTANT
Hyphaema
Bleeding into the anterior chamber of the eye
Haematoma after jugular sample. This dog had rodenticide toxicity.
Petechiae
Small pinprick haemorrhages
Tiny vessels bleed into the skin and mucus membranes
Ecchymoses
Haemorrhage under the skin.
5p coin size or bigger.
If you need to take blood from an animal but you are suspicious of a coagulopathy, what should you do?
Take blood from a leg (not jugular), put on a pressure bandage afterwards, and watch carefully.
Name of this test and how it helps us differentiate between petechiae and allergies
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
What named factor is involved in primary haemostasis and what does it do?
Von Willebrand Factor
Acts as the “glue” sticking platelets to each other and to the subendothelial matrix on a damaged vessel
Broad causes of primary haemostatic disorders
- Thrombocytopaenia
- Thrombocytopathia
- vWF deficiency
What tests can you do to diagnose a primary haemostatic disorder?
THIS IS IMPORTANT
- Platelet count
- Buccal mucosal bleeding time
- vWF antigen test
- Platelet function assays
Causes of thrombocytopaenia
- Defective platelet production
- Accelerated platelet removal
- Platelet sequestration or loss
Examples of diseases that could cause defective platelet production and therefore thrombocytopaenia
- Bone marrow neoplasia e.g. leukaemia
- Drug/chemical/toxin-induced bone marrow suppression
- Bone marrow infections esp. viral and rickettsial
Examples of diseases that could cause accelerated platelet removal and therefore thrombocytopaenia
- Immune-mediated thrombocytopaenia (IMTP) –> most common!
- Consumption in microangiopathic conditions e.g. DIC
Examples of diseases that could cause platelet sequestration or loss and therefore thrombocytopaenia
- Splenomegaly/vascular pooling
- Acute ongoing haemorrhage
What type of anaemia is observed here? How do we know this?
Regenerative anaemia
There are spherocytes and reticulocytes visible
How can IMTP be categorised?
Immune mediated thrombocytopaenia
* Primary = idiopathic
* Secondary = drug-induced/secondary to infection or neoplasia
IMTP signalment
- Young to middle aged, female dogs are over-represented
- Breeds: Cocker Spaniels, miniature/toy poodles, Old English sheepdogs
IMTP treatment
- 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
IMTP prognosis
- Can be good: 10-15% mortality, 10-40% relapse
- Negative prognostic indicators: melaena, high BUN
Thrombocytopathia
any kind of abnormal platelet function.
* Can be congenital or acquired.
* Clinical signs similar to thrombocytopenia, but platelet count is normal
Causes of thrombocytopathia
- Inherited thrombopathias
- Drug induced defects of platelet function e.g. several drugs including NSAIDs
- Platelet dysplasia (=neoplasia)
Diagnosis of thrombopathia
- 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.
Thrombopathia treatment
- No specific therapy
- Platelet transfusions are not possible
- Withdraw any drugs e.g. NSAIDs
- Treat symptomatically e.g. blood transfusions if marked anaemia
von Willebrand’s Disease (vWD)
- 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
Clinical signs of vWD
- 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
Diagnosis of vWD
- 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
Treatment of vWD
- 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.
Example of breed prone to vWD
Dobermann
Primary haemostasis
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
Secondary haemostasis
=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
1
aPTT
2
ACT
3
PT
Which factor has the shortest half-life and so will disappear first?
Factor VII
If your patient has a very high PT, but APTT is not so high, what are you suspicious of?
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
If fibrinogen is low, what does this suggest?
The patient is making a lot of clots and has used it all up
Factor 1 is also known as
fibrinogen
What is fibrinogen? Where is it made and how? Why might it be high/low?
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
What is produced from the breakdown of fibrinogen?
FDPs are produced from the breakdown of fibrinogen
Their presence indicates a pro-thrombotic state
Why might fibrinogen be increased?
- Elevated in inflammation
- Indication of DIC
- Potential bleeding/ making lots of clots
Why might fibrinogen be decreased?
- Viral and bacterial infection
- Kidney disease
- Traumatic injuries, surgery
- Cancer
- Heart disease
- Canine pregnancy, post-abortion
- DIC (due to consumption)
- Liver failure
How does rodenticide toxicity impact the coagulation cascade?
- 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
Clinical signs of rodenticide toxicity
- Clinical signs mimic coagulation factor deficiencies
- Spontaneous haemorrhage into body cavities
- SC haematomas
- Prolonged bleeding from wounds
Clinical signs of failure of secondary haemostasis
- Deep or cavity bleeds
- Mucus membranes may bleeding
- Sometimes single site of bleeding
- Haematomas are common
Petechiae / ecchymoses are rare in secondary haemostasis
Diseases of secondary haemostasis
- Congenital: haemophilia
- Acquired: Vitamin K antagonism (coumarin/ rodenticide toxicity), hepatic disease
Tests of secondary haemostasis
THIS IS IMPORTANT
- 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
What does ACT measure?
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
What does prothrombin time measure and what are the normal intervals for dogs and cats?
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
What does APTT measure and what are the normal intervals for dogs and cats?
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
What does TCT and what does an abnormal result indicate?
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
What does WBCT measure and what are the normal intervals?
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
What do specific factor assays measure and when would you use them?
Specific factor assays
* Measure the level of some individual clotting factors
* Used in the investigation of inherited coagulation disorders
What are the two forms of haemophilia and how will you diagnose them?
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
Treatment of haemophilia
- 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
How long does it take rodenticide toxicity to have an effect?
1-2 days
Can take as long as 1 week
Diagnosis of rodenticide toxicity
Initially PT/ OSPT is prolonged
Later APTT also increases
Treatment of rodenticide toxicity
- 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
True/false: advanced liver disease is a major differential that should be ruled out in cases of suspected coagulopathies.
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.
True/false: if you suspect advanced liver disease, taking a biopsy is a good first step to confirm your suspicions.
False
* They may bleed from the biopsy
* Test liver enzymes and coags first before you make the patient bleed out
What are some good general principles for management of a patient with either a pimary or secondary coagulopathy?
- 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.
