Haemodynamic disorders, thromboembolic disease and shock

haemostasis: definition

“A process involving platelets, clotting factors and endothelium that occurs at the site of vascular injury: which results in the formation of a blood clot to prevent/limit the extent of bleeding”.

basically how bleeding stops

excessive bleeding

Haemoabdomen (or haemoperitoneum ) – commonly secondary to:

• Abdominal trauma

• Neoplasia (e.g., ruptured hepatic/splenic haemangiosarcoma )

• Coagulopathies

• Splenic torsion/rupture

• Liver rupture or lobe laceration

• Ruptured aneurysms

• Post-surgical complications

excessive clotting

Saddle thrombus in a Maine coon cat

Underlying condition:

Hypertrophic cardiomyopathy (associated with MYBPC3 gene mutation). Other affected breed with gene mutation: Ragdolls.

can get very painful hindlimbs

Normal haemostasis

Normal haemostasis - 8 key steps

Vessel injury

↓

Vasoconstriction

↓

Platelet adhesion & aggregation

↓

Primary haemostatic plug

↓

Coagulation cascade

↓

Fibrin stabilises the plug

↓

Stable clot

↓

Clot removal/repair

1.Arteriolar vasoconstriction

Purpose: To reduce blood flow to site of injury

• Acts via an immediate neurogenic reflex in response to injury.

• Secretions of local factors (e.g., endothelin)

—A potent endothelium-derived vasoconstrictor

• Transient effect

• Bleeding would resume, if not for activation of platelets and coagulation factors

2 Primary haemostasis

Purpose: To “form a platelet plug”

• Exposure of subendothelial von Willebrand factor (vWF) + collagen, promotes platelet adherence and activation.

• Platelet activation

• Platelets: change shape from “small round discs” to “flat plates with spiky protusions”. to allow interaction with each other to form platelet plug

• Release of secretory granules to recruit more platelets

• Aggregation = primary haemostatic plug

2 Primary haemostasis - platelets

3 Secondary haemostasis - coagulation cascade

Now a platelet plug is formed…we need to build on this temporary seal by enzymatically depositing insoluble fibrin to make it stronger.

3 Secondary haemostasis - coagulation cascade

same way of showwing above

3 Secondary haemostasis - coagulation cascade -nsummary basically

Extrinsic pathway

• Triggered by tissue factor released/exposed after tissue injury

• Mainly Factor VII to activate Factor X (7 → 10)

Intrinsic pathway

• Uses factors already present in blood

o bacteria or damaged cell membranes, collagen / replicated in lab using glass

• Factors XII → XI → IX + VIII → to activate Factor X

12 → 11 → 9 + 8 → 10

Both extrinsic and intrinsic → common pathway

The intrinsic and extrinsic pathways are different routes to activate the common pathway.

Factors X → V → II (Prothrombin) → I (Fibrinogen)

10→5→ 2 → 1

X → thrombin → fibrinogen → fibrin → stable clot

coagulation cascade - secondary haemostasis

Additional key points to remember

• Factors XII (12), XI (11), X (10), IX (9), and VII (7) are

inactive factors that become activated (a) in the

cascade.

Calcium binds to factor II (2), VII (7), IX (9) and X (10).

• These same factors use Vitamin K as a co-factor

• The liver produces factors VIII (8), VII (7), and X (10),

as well as prekallikrein & high molecular weigh

kininogen (HMWK)

• Explaining why chronic liver disease (e.g., cirrhosis) results

in excessive bleeding.

3 Secondary haemostasis

Purpose: Deposition of insoluble fibrin

• Exposure of tissue factor

• Tissue factor = membrane bound procoagulant glycoprotein, normally expressed by subendothelial cells in vessel wall (e.g., smooth muscle + fibroblasts).

• Tissue factor binds and activates Factor VII (extrinsic pathway).

• Through the common pathway, inactive prothrombin is converted in active thrombin, which cleaves soluble fibrinogen into insoluble fibrin.

• Fibrin = platelet activator and forms a polymerised meshwork for platelets to bind.

4 Clot stabilisation and resorption

Purpose: To form a solid permanent plug that prevents further haemorrhage

• Polymerised fibrin and platelets undergo contraction

• Counter regulatory mechanisms (e.g. tissue plasminogen activator [tPA]) limit

clotting at the site and therefore led to clot resorption and tissue repair.

overall story of haemostasis in vascular injury

End of normal haemostasis - Limiting coagulation

Now the local blood clot is formed – the pro-coagulative state needs to be neutralised, so it does not exponentially disseminate throughout the body (equally as hazardous as uncontrolled bleeding).

limiting coagulation

need to know

remember antithrombin 3 -important enzyme to remember for protein losing nephropathies

and for hypercoagulation

haemorrhagic disorders

significance depends on:

volume

rate - slower bleeding is more manageable

location e.g brainstem bleeds more quickly can cause death

chronic blood loss:

iron deficiency

anaemia

pic shows top is bird bitten by tick so bleeding very quickly

bottom pic is snake with tumour bleeding for a few months

types of haemorrhage

Petechiae (pinpoint: <3mm)

very small

bison with malignant catole fever

Purpura (between 3 mm to 1 cm)

vary in size

Ecchymosis (large flat lesions: >1 cm).

stomach

haemorrhage

can cause pockets

haematomas - cerebral, splenic, and muscle (pics)

blood in cavities

thrombosis: Virchow’s triad

Describes the 3 main categories of factors that lead to blood clot formation (thrombosis):

Virchow’s Triad

1. Endothelial Injury (Vessel Wall Damage)

• Damage or irritation to the delicate inner lining (endothelium) of a blood

vessel.

• Why it causes clots: Injury exposes underlying procoagulant surfaces,

the release of clotting factors, and triggers vasoconstriction

• Common causes: Bacterial/fungal toxins, trauma (e.g., IV catheters), high

blood pressure, hypercholesterolaemia, emboli, and inflammation.

2) Stasis or Altered Blood Flow

• Slowed, pooled, or turbulent movement of blood through the vessels.

• Why it causes clots: Sluggish flow allows platelets to contact the

vessel wall and prevents clotting inhibitors from diluting.

• Common causes:

• Stasis: Atrial fibrillation, varicose veins, and prolonged immobility (e.g., bed rest

– via lack of skeletal muscle movement to assist pumping of blood through

veins).

• Turbulence: atherosclerosis/vessel narrowing, vasoconstriction/vasodilation,

aneurysms.

• Blood viscosity: Such as hyperviscosity (e.g., polycythaemia vera – increased

flow resistance)

2) Stasis or Altered Blood Flow

• Normal blood flow is laminar

2) Stasis or Altered Blood Flow

• Turbulence = ↑↑↑ platelet collisions + RBC adhesions

3) Hypercoagulability (Increased Clotting Tendency)

• An abnormal change in the blood's composition that makes it

prone to clotting too easily.

• Why it causes clots: The chemical balance tips heavily in favour

of forming fibrin and blood clots even without major vessel

trauma.

• Common causes: Inherited (e.g., genetic clotting disorders such

as “Factor V Leiden”) or acquired (e.g., disseminated cancer,

pregnancy, hormone therapy, and severe dehydration)

Arterial thrombus-no nlood cells going through - white

venous thrombous-blue/purple - no oxygen

possible fates of a thrombus

arrow shows clot in heart - fungus and disseminate elsewhere cos of stasis

top right is blood vessel with thrombus and bottom is histology

recanalisation

Veterinary Hypercoagulability & Thrombosis

Virchow's Triad examples in Veterinary Medicine

1. Hypercoagulability (Altered Blood Constituents)

• PLN / PLE: Severe hypercoagulability driven by loss of

Antithrombin III.

• IMHA: Cell lysis releases highly procoagulant erythrocyte

fragments.

• Hyperadrenocorticism (Cushing's): Overproduction of cortisol

spikes clotting factors (VIII, IX) while suppressing fibrinolysis.

• Neoplasia / Sepsis: Widespread tissue factor upregulation

triggers intravascular cascades

2. Endothelial Injury (Vessel Wall Damage)

• Heartworm (Dirofilaria immitis): Physical presence of adult

worms causes mechanical endothelial trauma in pulmonary

arteries.

• Sepsis / Endotoxemia: Bacterial lipopolysaccharides (LPS) and

severe systemic inflammation directly injure endothelial cells.

• Intravenous Catheters: Prolonged or rigid indwelling venous

lines trigger localised physical vessel wall release of tissue factor.

3. Stasis / Turbulence (Abnormal Blood Flow)

• Hypertrophic Cardiomyopathy (HCM): Dilation of the left atrium

secondary to left ventricular concentric hypertrophy results in

stagnant blood pooling = localised thrombogenesis.

• Gastric Dilatation-Volvulus (GDV): Volvulus compresses the

caudal vena cava, producing massive systemic venous stasis.

• Shock states: Severe systemic hypotension prompts localised

stagnation and microthrombi development.

• Prolonged Recumbency: Paralysed or heavily sedated large

animal patients develop localised stasis.

Pathological Embolism: Veterinary Classification

Classification by Composition ('What it is')

• Thromboemboli: Dislodged blood clots.

• Septic / Bacterial Emboli: Fragments of vegetative endocarditis valves (common in livestock

and dogs) carrying pathogens.

• Fibrocartilaginous (FCE): Ischemic herniation of intervertebral disc material into spinal cord

vasculature (mostly dogs).

• Parasitic Emboli: Fragments of adult heartworms (Dirofilaria immitis) obstructing the

pulmonary tree.

• Gas / Air Emboli: Iatrogenic introduction via improper IV catheter management or surgical

mishaps.

• Lipid / Fat Emboli: Microscopic fat droplets entering circulation post-severe long bone fracture

trauma.

Classification by Anatomic Destination ('Where it goes')

• Venous Circulation: Emboli originating in systemic peripheral veins heading to the right side of

the heart, followed by the lung = Pulmonary Thromboembolism (PTE).

• Arterial Circulation: Emboli originating in the left side of the heart to obstruct downstream

peripheral systemic arteries.

• Feline Aortic Thromboembolism (FATE): A major site where left cardiac clots lodge

themselves at the aortic trifurcation ('saddle thrombus'), causing hindlimb ischemia.

Embolism-Pulmonary embolism

• Acute death

Embolism-Systemic thromboembolism
• From intracardiac mural thrombi

• Lower extremities and brain

Embolism- Fat emboli

Embolism-Air emboli

Gas bubbles within the circulation (e.g., air or nitrogen)

Embolism-Amniotic fluid embolism

• Infusion of amniotic fluid/foetal tissue into maternal circulation

CNS embolism

Cartilage embolism (e.g., due to trauma).

Infarction: Mechanisms & Morphology

infarction

Factors that influence development of an infarct:

1. Anatomy of the vascular supply

2. Rate of occlusion

3. Tissue vulnerability to hypoxia

4. Hypoxemia

White (arterial) infarct

Dark red-purple (venous) infarct:

infarction

Stages of an infarct:

• Acute (fibrin-based)

• Chronic (features of fibrosis)

Pathology: Classifications of Shock

Cardiogenic Shock

• Core Defect: Myocardial pump failure.

• Mechanism: Inability to maintain sufficient cardiac output.

• Key Triggers: Acute myocardial infarction, tamponade, arrhythmias.

Hypovolemic Shock

• Core Defect: Critical loss of intravascular volume.

• Mechanism: Inadequate ventricular filling and stroke volume.

• Key Triggers: Acute hemorrhage, severe burns, extreme dehydration.

Septic Shock

• Core Defect: Microbial-driven systemic inflammation.

• Mechanism: Profound peripheral vasodilation and leaks.

• Key Triggers: Gramnegative bacteremia, advanced infections.

Neurogenic Shock

• Core Defect: Loss of autonomic vascular tone.

• Mechanism: Massive venous pooling from disrupted neural signals.

• Key Triggers: Highlevel spinal cord injuries, anesthetic accidents.

Pathophysiology: The Three Stages of Shock

1) Initial & Nonprogressive Stage

• Activation of central compensatory

mechanisms (baroreceptors,

catecholamines, renin-angiotensin

axis).

• Perfusion to vital organs is actively

maintained via peripheral

vasoconstriction.

• Cardiovascular parameters remain

clinically stable if underlying cause

is managed.

2) Progressive Stage

• Compensatory barriers fail, leading

to progressive tissue hypoperfusion.

• Shift to anaerobic glycolysis

results in lactic acid accumulation

and intracellular acidosis.

• Arterioles dilate, causing blood

pooling in microcirculation and

endothelial injury.

3) Irreversible Stage

• Widespread cellular injury and

membrane leakage prevent survival.

• Lysosomal enzyme release and

profound ATP depletion drive

widespread cell death.

• Clinical intervention fails to reverse

downstream multiple organ

dysfunction syndrome (MODS)

Cardiogenic shock

Hypovolemic shock

Low cardiac output due to low blood volume

• Massive haemorrhage

• Fluid loss from burns

Pathogenesis of Veterinary Septic Shock

01. The Trigger (Sepsis)

Microbial Invasion: Pathogens enter the bloodstream or localised tissue space. Endotoxins (LPS): Released from Gram-negative bacteria, driving the immune cascade.

Veterinary Examples:

• Canine: Ruptured pyometra or septic peritonitis.

• Feline: Advanced bite abscesses.

• Equine: Strangulating colic.

02. The Reaction (SIRS)

Systemic Inflammation:

Immune system overreacts, causing full-body inflammatory injury.

Vascular Dysfunction: Massive nitric oxide release triggers profound vasodilation & leaky vessels.

Clinical Signs: Hyper/hypothermia, severe tachycardia, and tachypnea.

03. The Failure (Septic Shock)

Cardiovascular Collapse: Critical loss of arterial blood pressure, causing tissue ischemia.

Cellular Hypoxia: Tissues lose perfusion, driving anaerobic metabolism and lactic acidosis.

End Stage: Multiple Organ Dysfunction Syndrome (MODS) and death.

Congestion, hyperaemia and haemorrhage: definitions

chronic

Oedema and effusion: overall causes

Oedema and effusion: 1) increased hydrostatic pressure

Oedema and effusion: 2) reduced plasma osmotic pressure

Oedema and effusion: 3) sodium and water retention

Oedema and effusion: 4) lymphatic obstruction

Oedema and effusion-Oedema

Oedema and Effusion: Pathological Effusions

(Anatomical Cavities & Diagnostic Classification (Exudates vs. Transudates))

1. Anatomical Cavity Classifications

• Thorax (Hydrothorax): Clear fluid accumulation inside the pleural space.

• Pericardium (Hydropericardium): Fluid filling the pericardial sac, risking

tamponade.

• Abdomen (Hydroabdomen / Ascites): Free fluid in the peritoneal space

(pictured right).

2. Fluid Classification & Diagnostics

• Exudate (Inflammatory fluid):

- High in proteins and high nucleated cell count.

- Directly associated with increased vascular permeability during active

inflammation.

• Transudate (Non-inflammatory hydrodynamic fluid):

- Protein-poor, translucent, and characteristically straw-coloured.

- Driven strictly by systemic hydrostatic or oncotic pressure imbalances.