Haemostasis

Question 1

Define haemostasis

Answer 1

Process by which blood clots form at sites of vascular injury

Question 2

What are the 3 stages of haemostasis

Answer 2

primary –> plt coming together & starting to make plug in damaged vessel wall

secondary –> coagulation cascade ensuring that plug is held together with fibrin strands

tertiary (fibrinolysis) –> after it has served its purpose it needs to be dissolved

Question 3

What are the main cellular components of primary haemostasis?

Answer 3

Platelets & endothelial cells (vWF)

Question 4

Describe the events that occur in primary haemostasis

Answer 4

1. Adhesion
   - Platelets bind to collagen & vWF at injury sites via surface receptors
2. Activation
   - Platelets change shape to increase surface area
   - Degranulation releases ADP, clotting factors (V & VIII) & phospholipids
   - Thromboxane A2 promotes further activation & aggregation
3. Aggregation
   - Platelets link via fibrinogen bridges, forming platelet plug

Question 5

What are the therapeutic interventions that can be undertaken during primary haemostasis?

Answer 5

Aspirin/NSAIDs → Inhibit thromboxane A2 production.

Clopidogrel → Blocks ADP receptor to reduce platelet activation.

Question 6

What tests can be done to evaluate primary haemostasis?

Answer 6

Platelet count & PCT (plateletcrit)

Buccal mucosal bleed time (BMBT)

vWD: vWf-antigen, vWf activity, genetic testing (breed-specific)

Platelet function: aggregometry, flow cytometry, inherited platelet dysfunction –> genetic testing (breed-specific)

Question 6

What condition causes us to suspect a problem with primary haemostasis

Answer 6

Petechiae

Petechiae are caused by pinpoint cutaneous & mucosal haemorrhages from small blood vessels subjected to daily minor trauma, e.g. those supplying mucosal surfaces

Question 7

What are the most common disorders of primary haemostasis?

Answer 7

Thrombocytopenia (reduced platelet number)

Thrombocytosis (increased platelet number)

Thrombopathia (abnormal platelet function (uncommon))

von Willebrand Disease

Question 8

What are the possible causes of thrombocytopenia?

Answer 8

Inherited
- E.g. CKCS, Greyhounds
- usually not severe

Acquired
- Decreased production (bone marrow disease)
- Destruction (e.g., immune-mediated - ITP)
- Consumption (e.g., DIC)
- Sequestration
- Loss

Question 9

What are the 2 forms of ITP (cause of thrombocytopenia)?

Answer 9

Primary (e.g. Cocker Spaniels)

Secondary (e.g. infectious diseases, neoplasia)

Very low platelet count PT, aPTT & TCT within normal reference intervals

Question 10

What are the possible causes of thrombocytosis

Answer 10

Acquired –> Increased platelet production
- Neoplasia (e.g., essential thrombocythaemia)
- Drugs (e.g., vincristine, adrenaline, glucocorticoids)
- Reactive (cytokine-driven) –> secondary to inflammation, neoplasia, GI disease
- Iron deficiency

Acquired –> decreased clearance
- splenectomy

Question 11

What are the clinical signs & test results of thrombopathia

Answer 11

bleeding, platelet count WRI or mildly reduced, vWf:Ag concentration WRI, abnormal BMBT

Question 12

What is the most common inherited bleeding disorder and what is the most common clinical sign?

Answer 12

Von Willebrand Disease (vWD) → Deficient/abnormal vWF, affecting platelet adhesion

e.g. Dobermann

Young age –> excessive bleeding at teething, spaying/neutering

Question 13

How is vWD diagnosed?

Answer 13

Measurement of vWf:Ag concentrations, genetic tests (selected breeds), BMBT

Question 14

What are the steps in secondary haemostasis?

Answer 14

1. Intrinsic pathway
   - Triggered by exposure to negatively charged surfaces (e.g., basement membrane, collagen, platelets).
   - Factor XII → Activates Factor XI
   - Factor XIa → Activates Factor IX
   - Factor IXa + Factor VIIIa + Calcium + Platelets → Activates Factor X
2. Extrinsic Pathway
   - Triggered by Tissue Factor (TF) release from damaged tissue.
   - TF binds Factor VII, forming TF-FVIIa complex
   - TF-FVIIa activates Factor X
3. Common Pathway
   - Factor Xa + Factor Va + Calcium + Platelets (Prothrombinase Complex) → Converts Prothrombin (Factor II) to Thrombin (Factor IIa)
   - Thrombin (Factor IIa) converts Fibrinogen (Factor I) into Fibrin (Factor Ia)
   - Factor XIIIa cross-links fibrin, stabilizing the clot

Question 15

What is the main anticoagulant of the clotting cascade?

Answer 15

Antithrombin (AT) inhibits factor Xa and thrombin

Question 16

Describe in vivo secondary haemostasis?

Answer 16

1. Initiation
   - Tissue Factor (TF) + Factor VIIa → Activates Factor IX & Factor X → Small thrombin production
2. Amplification
   - Thrombin activates platelets & Factors V, VIII, XI, amplifying clot formation
3. Propagation
   - Large thrombin burst → Fibrin formation.
4. Fibrin formation

Question 17

What is essential for fibrin formation & initiation of fibrinolysis?

Answer 17

Thrombin

Question 18

What is required for coagulation to occur?

Answer 18

Calcium & activated platelets

Question 19

Where are most coagulation factors synthesised?

Answer 19

Liver

Question 20

What do factors II, VII, IX & X require?

Answer 20

Vitamin K

Question 21

What are the most common disorders of secondary haemostasis?

Answer 21

Hypocoagulability (bleeding disorder

Hypercoagulability (thrombosis)

Question 22

Describe hypocoagulability

Answer 22

Decreased fibrin formation due to coagulation factor or vit K deficiency

Bleeding from large vessels → haematomas (skin, muscle, subcutaneous tissue)

Haemorrhage into body cavities → haemarthrosis, haemoperitoneum

Question 23

Describe hypercoagulability (thrombosis)

Answer 23

Excessive thrombin generation due to aberrant activation of secondary haemostasis

Causes:
- Massive endothelial injury
- TF expression on monocytes or cancer cells
- Loss/decreased production of inhibitors (e.g., AT)
- High fibrinogen & Factor VIII contribute

Difficult to diagnose due to lack of sensitive tests

Question 24

What tests can be done to evaluate secondary haemostasis? | state test name, pathways, activator & what it tests

Answer 24

Prothrombin Time (PT) – Extrinsic + common - Activator: tissue thromboplastin - Tests Factor VII + common pathway Activated Partial Thromboplastin Time (aPTT) – Intrinsic + common - Activator: kaolin/silica - Tests Factors XII, XI, IX, VIII + common Activated Clotting Time (ACT) – Intrinsic + common - Activator: diatomaceous earth - Uses whole blood, less sensitive than aPTT Thrombin Clotting Time (TCT) – Common only - Measures fibrinogen → fibrin (via thrombin)

Question 25

What is an important inflammatory indicator in horses?

Answer 25

Fibrinogen

Question 26

What blood tube is used when assessing haemostasis?

Answer 26

Citrate blood tube (allows for reversible calcium binding) - Proper fill to ensure correct citrate ratio - Prompt analysis or centrifuge & ship cold citrate plasma to lab

Question 27

What is the most common inherited disorder of secondary haemostasis in cats?

Answer 27

Factor XII Deficiency Prolonged aPTT but no clinical bleeding tendencies

Question 28

How do Haemophilia A and B differ?

Answer 28

Haemophilia A → Factor VIII Deficiency - esp. German Shepherds Haemophilia B → Factor IX Deficiency Both are sex-linked (males affected) Cause haematomas, surgical bleeding, haemarthrosis Diagnosis: - Prolonged aPTT, normal PT. - Confirmed by specific factor testing

Question 29

What are the most common acquired disorders of secondary haemostasis?

Answer 29

Anticoagulant rodenticide toxicosis Metabolic diseases (e.g., liver disease, neoplasia)

Question 30

Why does rodenticide toxicosis cause coagulation disorders?

Answer 30

Rodenticides inhibit Vit K epoxide reductase (VKOR), preventing recycling of vit K This stops activation of Factors II, VII, IX, and X, leading to prolonged clotting times

Question 31

Which clotting test is prolonged first in rodenticide toxicity?

Answer 31

Prothrombin Time (PT) is prolonged first because Factor VII has the shortest half-life aPTT is prolonged later as other vit K-dependent factors deplete

Question 32

How can liver dysfunction affect coagulation?

Answer 32

Liver produces most coagulation factors Liver disease can lead to factor deficiencies similar to vit K deficiency Blood chemistry will show liver pathology markers

Question 33

How can vitamin K absorption be impaired?

Answer 33

Vit K is lipid-soluble, so conditions affecting fat absorption can cause deficiency: - Biliary obstruction (cholestasis) → Reduces bile salts needed for fat absorption - Malabsorption syndromes (e.g., exocrine pancreatic insufficiency, lymphangiectasia)

Question 34

What is fibrinolysis? What does it produce?

Answer 34

Breakdown of fibrin clots by plasmin Produces fibrin degradation products, including D-dimer

Question 35

What condition causes delayed bleeding in Greyhounds after routine surgery?

Answer 35

Excessive fibrinolysis or weak clot formation Bleeding starts days after surgery (e.g., spay, castration) Suggests clots dissolve too early or too quickly

Question 36

How can excessive fibrinolysis in Greyhounds be treated?

Answer 36

Plasminogen to plasmin blockers are effective: - Tranexamic acid (TXA) - Epsilon aminocaproic acid (EACA)

Question 37

What is Disseminated Intravascular Coagulation (DIC)?

Answer 37

global haemostasis disorder where multiple clotting abnormalities occur It's never primary disease, but always secondary to inflammation, sepsis, trauma, or endothelial injury (e.g., Angiostrongylus infection)

Question 38

What causes DIC?

Answer 38

Uncontrolled intravascular thrombus formation & breakdown Triggered by large amounts of Tissue Factor (TF) & procoagulant inflammatory cytokines Leads to platelet & coagulation factor consumption, causing both thrombosis & bleeding

Question 39

How is DIC diagnosed?

Answer 39

No single test confirms DIC → Requires a combination of abnormal haemostasis results Serial testing (24–48 hours apart) in at-risk patients is key Early (thrombotic) stage: - Decreasing platelet count & antithrombin (AT) - Increasing PT, aPTT & D-dimer

Question 40

What are the key lab findings in the thrombo-haemorrhagic phase of DIC?

Answer 40

Thrombocytopenia Prolonged PT and aPTT Increased D-dimer concentration (fibrinolysis marker) Low AT (antithrombin) activity

Question 41

Why are D-dimers important in DIC?

Answer 41

D-dimers are fibrin degradation products produced during fibrinolysis Increased D-dimer levels indicate excessive clot formation and breakdown Important for tracking disease progression and diagnosis

Question 42

What is viscoelastic testing used for in haemostasis?

Answer 42

global test of haemostasis that assesses all 3 stages (primary, secondary, and fibrinolysis) Produces graphical tracings that show clot formation, firmness & breakdown Different tracing patterns help diagnose coagulopathies, hypercoagulability & fibrinolysis abnormalities

Question 43

What are the common types of viscoelastic tests?

Answer 43

Thromboelastography (TEG) Thromboelastometry (ROTEM) Viscoelastic Coagulation Monitor (VCM)