Haemostasis Flashcards
Define haemostasis
Process by which blood clots form at sites of vascular injury
What are the 3 stages of haemostasis
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
What are the main cellular components of primary haemostasis?
Platelets & endothelial cells (vWF)
Describe the events that occur in primary haemostasis
- Adhesion
- Platelets bind to collagen & vWF at injury sites via surface receptors - Activation
- Platelets change shape to increase surface area
- Degranulation releases ADP, clotting factors (V & VIII) & phospholipids
- Thromboxane A2 promotes further activation & aggregation - Aggregation
- Platelets link via fibrinogen bridges, forming platelet plug
What are the therapeutic interventions that can be undertaken during primary haemostasis?
Aspirin/NSAIDs → Inhibit thromboxane A2 production.
Clopidogrel → Blocks ADP receptor to reduce platelet activation.
What tests can be done to evaluate primary haemostasis?
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)
What condition causes us to suspect a problem with primary haemostasis
Petechiae
Petechiae are caused by pinpoint cutaneous & mucosal haemorrhages from small blood vessels subjected to daily minor trauma, e.g. those supplying mucosal surfaces
What are the most common disorders of primary haemostasis?
Thrombocytopenia (reduced platelet number)
Thrombocytosis (increased platelet number)
Thrombopathia (abnormal platelet function (uncommon))
von Willebrand Disease
What are the possible causes of thrombocytopenia?
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
What are the 2 forms of ITP (cause of thrombocytopenia)?
Primary (e.g. Cocker Spaniels)
Secondary (e.g. infectious diseases, neoplasia)
Very low platelet count PT, aPTT & TCT within normal reference intervals
What are the possible causes of thrombocytosis
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
What are the clinical signs of thrombopathia
bleeding, platelet count WRI or mildly reduced, vWf:Ag concentration WRI, abnormal BMBT
What is the most common inherited bleeding disorder and what is the most common clinical sign?
Von Willebrand Disease (vWD) → Deficient/abnormal vWF, affecting platelet adhesion
e.g. Dobermann
Young age –> excessive bleeding at teething, spaying/neutering
How is vWD diagnosed?
Measurement of vWf:Ag concentrations, genetic tests (selected breeds), BMBT
What are the steps in secondary haemostasis?
- 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 - Extrinsic Pathway
- Triggered by Tissue Factor (TF) release from damaged tissue.
- TF binds Factor VII, forming TF-FVIIa complex
- TF-FVIIa activates Factor X - 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
What is the main anticoagulant of the clotting cascade?
Antithrombin (AT) inhibits factor Xa and thrombin
Describe in vivo secondary haemostasis?
- Initiation
- Tissue Factor (TF) + Factor VIIa → Activates Factor IX & Factor X → Small thrombin production - Amplification
- Thrombin activates platelets & Factors V, VIII, XI, amplifying clot formation - Propagation
- Large thrombin burst → Fibrin formation. - Fibrin formation
What is essential for fibrin formation & initiation of fibrinolysis?
Thrombin
What is required for coagulation to occur?
Calcium & activated platelets
Where are most coagulation factors synthesised?
Liver
What do factors II, VII, IX & X require?
Vitamin K
What are the most common disorders of secondary haemostasis?
Hypocoagulability (bleeding disorder
Hypercoagulability (thrombosis)
Describe hypocoagulability
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
Describe hypercoagulability (thrombosis)
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
What tests can be done to evaluate secondary haemostasis?
Prothrombin Time (PT) – Extrinsic & Common Pathway
- Activator: Tissue thromboplastin (mimics Tissue Factor)
- Tests Factor VII + common pathway
Activated Partial Thromboplastin Time (aPTT) – Intrinsic & Common Pathway
- Activator: Kaolin, silica, or ellagic acid (stimulates Factor XII)
- Tests Factors XII, XI, IX, VIII + common pathway
Activated Clot Time (ACT) – Intrinsic & Common Pathway
- Activator: Diatomaceous earth
- Requires whole blood (platelets & calcium)
- Less sensitive than aPTT but used for quick in-house testing
Thrombin Clot Time (TCT) – Common Pathway Test
- Measures time for thrombin to convert fibrinogen to fibrin
- Assesses fibrinogen function & common pathway efficiency
What is an important inflammatory indicator in horses?
Fibrinogen
What blood tube is used when assessing haemostasis?
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
What is the most common inherited disorder of secondary haemostasis in cats?
Factor XII Deficiency
Prolonged aPTT but no clinical bleeding tendencies
How do Haemophilia A and B differ?
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
What are the most common acquired disorders of secondary haemostasis?
Anticoagulant rodenticide toxicosis
Metabolic diseases (e.g., liver disease, neoplasia)
Why does rodenticide toxicosis cause coagulation disorders?
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
Which clotting test is prolonged first in rodenticide toxicity?
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
How can liver dysfunction affect coagulation?
Liver produces most coagulation factors
Liver disease can lead to factor deficiencies similar to vit K deficiency
Blood chemistry will show liver pathology markers
How can vitamin K absorption be impaired?
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)
What is fibrinolysis?
Breakdown of fibrin clots by plasmin
Produces fibrin degradation products, including D-dimer
What condition causes delayed bleeding in Greyhounds after routine surgery?
Excessive fibrinolysis or weak clot formation
Bleeding starts days after surgery (e.g., spay, castration)
Suggests clots dissolve too early or too quickly
How can excessive fibrinolysis in Greyhounds be treated?
Plasminogen to plasmin blockers are effective:
- Tranexamic acid (TXA)
- Epsilon aminocaproic acid (EACA)
What is Disseminated Intravascular Coagulation (DIC)?
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)
What causes DIC?
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
How is DIC diagnosed?
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
What are the key lab findings in the thrombo-haemorrhagic phase of DIC?
Thrombocytopenia
Prolonged PT and aPTT
Increased D-dimer concentration (fibrinolysis marker)
Low AT (antithrombin) activity
Why are D-dimers important in DIC?
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
What is viscoelastic testing used for in haemostasis?
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
What are the common types of viscoelastic tests?
Thromboelastography (TEG)
Thromboelastometry (ROTEM)
Viscoelastic Coagulation Monitor (VCM)
