Haemostasis

Question 1

What are the 3 stages of haemostasis

Answer 1

Question 2

What cellular components are involved in primary haemostasis?

Answer 2

Platelets
Endothelial cells (vWF/Von Willebrand factor)

Question 3

Describe the events that happen in primary haemostasis

Answer 3

Adhesion: platelets bind to exposed subendothelial matrix proteins (collagen and vWF) through specific surface receptors
Activation: platelets change shape and degranulated released ADP, thromboxane and clotting factors which recruit more platelets
Aggregation: fibrinogen mediates the binding of adjacent platelets forming a temporary platelet plug

Question 4

What are the possible therapeutical interventions for primary haemostasis

Answer 4

aspirin/NSAIDs => inhibition of thromboxane production
Clopidogrel => ADP receptor agonist

Question 5

What are the clinical signs of ineffective primary haemostasis?

Answer 5

Petechiae (small spots of bleeding under skin or MM)
Ecchymosis (bruise)
Purpura (small, red flat spots)
Haematuria
Epistaxis (Nosebleed)

Question 6

What tests can be used to assess primary haemostasis?

Answer 6

Question 7

Give examples of disorders of primary haemostasis

Answer 7

Thrombocytopenia (reduced platelet number)
Thrombocytosis (increased platelet number)
Thrombopathia (abnormal platelet function)
Von Willebrand Disease (vWD)

Question 8

Which breeds are predisposed to inherited thrombocytopenia?

Answer 8

Cavalier King Charles Spaniel
Greyhounds

Question 9

Describe acquired thrombocytopenia

Answer 9

Decreased production of platelets
Destruction of platelets (immune mediated - primary or secondary e.g., immune thrombocytopenia)
Consumption of platelets e.g., DIC
Sequestration of platelets
Loss of platelets

Question 10

Describe thrombocytosis

Answer 10

Increased platelet production:
- neoplasia
- drugs (adrenaline, glucocorticoids)
- reactive (cytokine driven) secondary to inflammation, neoplasia, GI disease
- iron deficiency
Decreased clearance:
- splenectomy

Question 11

What are the clinical signs of thromboplasia

Answer 11

Bleeding
Platelet count within reference interval or slightly reduced
vWf:Ag within reference interval
abnormal BMBT (buccal mucosal bleeding time)

Question 12

Describe von Willebrand disease

Answer 12

Most common inherited disorder of haemostasis (e.g., Dobermann)
Deficient or abnormal vWf
Measurement of vWf:Ag concentrations, genetic tests (selected breeds), BMBT
Signs: Young age -> excessive bleeding at teething, spaying/neutering

Question 13

What is secondary haemostasis?

Answer 13

Coagulation: formation of fibrin by coagulation factors on the surface of activated platelets
3 pathways: intrinsic, extrinsic, common

Question 14

Describe the intrinsic pathway of secondary haemostasis

Answer 14

exposure of basement membrane/collagen or negative charges activates factor XII which activates a cascade of clotting factors (XI, IX, VIIIa) to initiate the common pathway to form fibrin

This pathway takes longer

Question 15

Describe the extrinsic pathway of secondary haemostasis

Answer 15

Contact with tissue factor (thromboplastin) activated TF (tissue factor) and factor VII complex to initiate the common pathway to form fibrin

Question 16

Describe the common pathway of secondary haemostasis

Answer 16

Clotting factor X -> V -> thrombin -> fibrin

Question 17

How secondary haemostasis be inhibited?

Answer 17

Antithrombin inhibits factor Xa and thrombin - acts as an anticoagulant

Question 18

Describe the cell-based model of coagulation

Answer 18

Initiation:
- tissue factor expressed on fibroblasts bind to factor VII forming TF-FVIIa complex
- TF-FVIIa complex activates factor X => produces a small amount of thrombin
Amplification:
- thrombin amplifies its own production via activation of factor XI and the co-factors V and VIII
Propagation:
- burst of thrombin generation on platelet surfaces
Fibrin formation

Question 19

What is required for coagulation to occur?

Answer 19

Ca and activated platelets
Vit K required for synthesis of functional factors II, VII, IX and X

Question 20

Where are coagulation factors synthesised?

Answer 20

liver

Question 21

What is the effect of warfarin and rodenticide on coagulation?

Answer 21

inhibit the recycling of vitamin K resulting in a relative vitamin K deficiency -> anticoagulant effect (vit K required for production of some clotting factors)

Question 22

What are signs of hypocoagulability?

Answer 22

Haematoma
haemorrhage

Question 23

What are signs of hypercoagulability?

Answer 23

thrombosis

Question 24

What tests can be done to assess secondary haemostasis?

Answer 24

Prothrombin time (PT)
Activated Partial prothrombin time (aPTT)
Activated clot time (ACT)
Thrombin clot time (TCT)
Fibrinogen

Question 25

Describe the prothrombin time (PT) test

Answer 25

Assesses the extrinsic pathway by testing factor VII and the common pathway Tissue thromboplastin is added to blood to activate the cascade

Question 26

Describe the activated partial thromboplastin time test

Answer 26

Assesses the intrinsic and common pathways An activator is added to a blood sample (kaolin, silica, ellagic acid) to initiate the intrinsic pathway A platelet substitute (cephalin) is added to provide a phospholipid surface for clotting reactions Ca is added to allow the cascade to proceed Time to clot is recorded

Question 27

Describe the activated clot time test

Answer 27

Tests the intrinsic and common pathways Available as an automated in-clinic test Tests whole blood - requires patient platelets and calcium Activator = diatomaceous earth

Question 28

Describe the thrombin clot time test

Answer 28

Tests common pathway Time taken for a thrombin solution to convert fibrinogen to fibrin

Question 29

Describe the use of testing fibrinogen in assessing coagulation

Answer 29

Measures the balance between production (inflammation) and consumption (coagulation) Direct check of common pathway

Question 30

Give examples of methods of measuring fibrinogen

Answer 30

Modified TCT (clotting time compared to standard curve - TCT is inversely proportional to fibrinogen conc) Refractometer pre and post heat precipitation of fibrinogen Fibrinogen antigen (specialised lab needed) Total protein plasma vs serum

Question 31

Test results: PT = increased aPTT = normal TCT = normal Where is the defect in secondary haemostasis and what could be causing it?

Answer 31

Extrinsic pathway - FVII Inheritance, Vit K absence or antagonism (e.g., warfarin), DIC, liver failure

Question 32

Test results: PT = normal aPTT = increase TCT = normal Where is the defect in secondary haemostasis and what could be causing it?

Answer 32

Intrinsic pathway - FXII, XI, IX, VIII Inherited, vit K absence or antagonism, liver failure, DIC

Question 33

Test results: PT = normal aPTT = normal TCT = increased Where is the defect in secondary haemostasis and what could be causing it?

Answer 33

Fibrinogen conversion to fibrin Hypo/dysfibrigonaemia

Question 34

Test results: PT = increased aPTT = increased TCT = normal Where is the defect in secondary haemostasis and what could be causing it?

Answer 34

Common pathway - FX, FII, FV Defects in multiple pathways Inherited, Vit K absence or antagonism, liver failure, DIC

Question 35

Test results: PT = increased aPTT = increased TCT = increased Where is the defect in secondary haemostasis and what could be causing it?

Answer 35

Fibrinogen conversion to fibrin Defects in multiple pathways Severe hypofibrinogenaemia (e.g., liver failure, inherited, DIC) Excessive heparin therapy

Question 36

Give examples of inherited disorders of secondary haemostasis

Answer 36

Haemophilia A Haemophilia B Factor XII deficiency (Hageman trait)

Question 37

Describe inherited haemophilia A

Answer 37

FVIII Dogs (males - sex linked) Prolonged aPTT, PT WRI

Question 38

Describe inherited haemophilia B

Answer 38

FIX Dogs (males - sex linked) Prolonged aPTT, PT WRI

Question 39

Describe factor XII deficiency (Hageman trait)

Answer 39

Cats Prolonged aPTT, no bleeding tendencies

Question 40

Give examples of acquired disorders of secondary haemostasis

Answer 40

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

Question 41

Describe the effect of vitamin K inhibition on secondary haemostasis

Answer 41

Factors II, VII, IX and X are vit K dependent Factor VII has very short half-life => extended PT (very) and aPTT (moderately)

Question 42

Give examples of possible sources of vitamin K inhibition leading to impacted coagulation

Answer 42

Rodenticide toxicosis Liver dysfunction Poor Vit K uptake (e.g., cholestasis, problems in biliary flow, malabsorption)

Question 43

What is fibrinolysis?

Answer 43

the dissolution of the fibrin clot by plasmin => formation of D-dimers

Question 44

Describe fibrinolysis in greyhounds

Answer 44

Fibrinolysis occurs too early or too quickly => bleeding a few days after surgery blockers e.g., tranexamic acid, are effective prevention

Question 45

What is DIC?

Answer 45

Disseminated intravascular coagulation = uncontrolled intravascular thrombus formation and breakdown Not a primary disease - DIC is the result of failed haemostasis

Question 46

Describe the features of DIC

Answer 46

Secondary to inflammation, endothelial injury, trauma, bacterial sepsis Exposure to large amounts of tissue factor and procoagulant inflammatory cytokines Microthrombi produced (hard to detect) Consumption of platelets and coagulation factors leads to abnormal primary and secondary haemostasis as DIC advances

Question 47

What are the signs of DIC?

Answer 47

Thrombo-haemorrhagic clinical signs Red cell fragmentation on smears Thrombocytopenia Prolonged PT and aPTT Hypofibrinogenaemia Increased D-dimer concentration

Question 49

Give examples of global tests of haemostasis

Answer 49

Viscoelastic testing: - thromboelastography (TEG) - thromboelastrometry (TOTEM) - viscoelastic coagulation monitor (VCM)

Question 50

What are the terms used to describe the findings of viscoelastic tests of haemostasis?

Answer 50

Normocoagulable Hypercoagulable Hypocoagulable Excessive fibrinolysis Reduced fibrinolysis