General Veterinary Pathology

THROMBOSIS

• Formation of clotted mass of blood within the cardiovascular system
• Clotted mass – Thrombus (singular) and thrombi (plural)

Differences between thrombus and blood clot

Thrombus	Blood clot
Formation
Blood vessels Platelets Blood clotting system	Blood clotting system
Composition
Platelets Fibrin	Only fibrin
Prognosis
Life threatening	Life saving

Causes for

• Injury to endothelium
  • Trauma : lacerations, contusion, rupture, i/r injection
  • Toxins : Streptococci, erysipelothrix (vegetations)
  • Degenerations : Atherosclerosis (damage to intima)
  • Viruses : Hog cholera virus
  • Parasites : Strongylus vulgaris in anterior mesenteric artery in horses
  • Tumours : Invading tumours

Mechanism of thrombus formation

• Active
• Antithrombotic factors and prothrombotic factors are seen on surface of endothelium
• Passive
• Endothelium is thromboresistant wheras subendothelial connective tissue is highly thrombogenic.
• Subendothelial onnective tissue consists of collagen, elastic, fibrinonectin, laminin glycosoaminoglycans and thrombosporin.
• Damage to endothelium exposes the subendothelial connective tissue and activates intrinsic blood clotting pathway and platelet adhesion.

Antithrombotic factors (present on endothelial cells) - Inhibit thrombosis

• Anticoagulant properties
  • Thrombo modulin - Protect against action of heparin and thrombin which converts fibrinogen to fibrin
• Anti platelet properties - Inhibit platelet aggregation
  • Prostacyclin (PGI2)
  • Nitric oxide (NO₂)
• Fibrinolytic properties
  • Tissue plasminogen activator (tPAs) - Promotes fibrinolytic activity in blood and reacts against blood clots

Thrombotic factors

• Tissue factor (Thromboplastin)
  • Present on endothelium in small amounts
  • Activate extrinsic clotting pathway
  • Stimulated by
    • Endotoxins
    • Cytokines (IL – 1)
    • Tumour necrosis factor (TNF)
• von Willebrand factor (vWF)
  • Protein helps in platelet adherence thrombus
• Platelet Activating Factor (PAF)
  • Helps in platelet aggregation thrombus
• Inhibitor of Plasminogen Activator
  • Prevents fibrinolysis thrombus

Normal homeostasis: There will be a balance between antithrombotic and prothrombotic factors in normal endothelium.

Thrombus formation

• Increase prothrombotic factors
• Decrease antithrombotic factors

Alterations in constituents of blood

• Increase in number of platelets
  • Parturition
  • surgery
• Increase in adhesiveness of platelets
  • Parturition
  • Surgery
• Decrease in heparin (anticoagulant) in diseases
• Increased plasma fibrinogen and prothrombin
  • Trauma
• Increased viscosity of blood
  • Dehydration
  • Polycythemia
• Sludging of blood
  • Clumping of cells
• Increased fragility of RBCs
• Increased cortisone therapy – Rheumatoid arthritis - Increase blood lipids - Increase platelet aggregation - Coronary thrombosis

Alterations in normal blood flow

• Slowing of blood flow results in platelet aggregation
• Turbulence damage endothelium

Types of thrombus

• Arterial thrombus
• Venous thrombus
• Cardiac thrombus

Causes for slowing of blood

• Chronic venous congestion venous stasis
• Old and debilitated animals
• Varicose veins

Comon sites for thrombosis

• Animals
• Scrotal plexus - horses
• Vascular sinuses – horse and cows (Nasal passage)
• Large veins of Broad ligament of uterus – cow
• Anterior mesenteric artery - horses
• Humans
• Leg veins – Congestive heart failure, bed ridden patients

CLASSIFICATION OF THROMBI

I. Based on location within blood vascular system

1.Cardiac thrombi

• Mural thrombus: Seen on the wall of left auricle
• Bovines - black quarter
• Caused by Clostridium chauvoei
• Valvular thrombus
• Pigs – Streptococcus pyogenes, Erysipelothrix rhusiopathiae
• Cattle– Cornybacterium pyogenes
• Horses– Streptococcus equi
• Ball thrombus: Seen in auricle - Unattached. If it is large,it causes valvular obstruction

2. Arterial thrombi

• Located within arteries
• Common in domestic animals
  • Horses : Strongylus vulgaris larvae in anterior mesenteric artery
  • Dogs : Spirocerca lupi in aorta
  • Cattle: Onchocerca armillata in aorta

3. Venous thrombi

• Phlebothrombosis
• Common in bed ridden patients
• Rare in animals
• Seen in recumbent calves

Leg veins collapse and press against hard surface. Endothelium gets damaged and thromboplastin is released resulting in thrombus formation. In general passive hyperaemia, veins will be distended and leads to slowing of blood which favours thrombus formation.

Locations

• Human - Femoral, popliteal, iliac veins
• Animals
• Nasal vascular sinuses – Cow, horses
• Veins of broad ligament – Cow
• Scrotal plexus – Horses

4. Capillary thrombi

• Seen in inflammation
• Injury to endothelium

5. Lymphatic thrombi

• Seen in lymphatics draining inflammation area
• Beneficial

II. Classification based on location within heart or bood vessels

• Mural thrombi - Attached to wall of heart / blood vessel
• Valuvlar thrombi - Valves
• Lateral thrombi - Attached to one side of blood vessel
• Occlusive thrombi - Attached to entire circumference of vessel
• Saddle thrombi -Site of bifurcation of blood vessel
• Canalised thrombi - New blood channel is formed through clot

III. Classification based on infectious agent

• Septic thrombi - Bacteria
• Aseptic thrombi - Without bacteria / parasites
• Parasitic thrombi - Strongylus vulgaris (Horses) and Dirofilaria immitis (Dogs)

IV. Classification based on colour of thrombi

• Pale / White Thrombi - composed of platelets and are seen in heart / aorta
• Red Thrombi – composed of platelets / fibrin, RBCs and WBCs and are seen in veins ( Commonly seen)
• Mixed Thrombi –Mixture of White and red thrombi (White - Formed during fast flow of blood; Red - Formed during sluggish flow)
• Laminated thrombi
  • Type of mixed thrombi
    • Excessive exercise - increase blood flow to legs – White Thrombus
    • Rest - increase blood flow to legs - Red Thrombus

Fate of thrombus

• Propagation : Enlargement - obstruction of vessel
• Contraction : Shrinkage of thrombus may occur due to contraction of fibrin
• Embolus : Carried to other sites; and cause dangerous infarction
  • Enzymes from WBCs / platelets digest thrombi and emboli are formed
• Abscessation : Pyogenic bacteria in thrombus may gives rise to bacterial emboli
• Resolution : Fibrinolysis
  • Fresh thrombus – Complete digestion
  • Old thrombus – incomplete digestion
• Organization & Canalisation

Significance and results

• Negligible effects - Jugular vein; carotid arteries
• Beneficial effects - Control of haemorrhages
• Harmful effects - Vessel without collateral circulation
• Infarction
• Embolism
• Passive hyperemia
• Lymphoedema
• Aneurysm – Strongylus vulgaris
• Gangrene – intestinal thrombus
• Colic, lameness
• Septicaemia / Death

Character	Thrombus	Postmortem clot
Size	Fills vessels	Small
Consistency	Dry & friable	Smooth / glistening
Color	White, red, mixed	Red / yellow
Attachment	Yes	No
Endothelium	Damaged	Undamaged
Composition	Platelets	Fibrin
Rapidity of blood flow	Formed in flowing stream	Stagnant stream
Animal	Living	Dead
Organization	Yes	No
Structure	Laminated (Line of Zahn)	Homogenous