Thrombosis, Embolism and Infarction Flashcards
Define thrombosis
- A thrombus is a solidification of blood contents that forms within the vascular system during life
- Thrombosis is a pathological process. It denotes the formation of a thrombus within the noninterupted vascular system
What are the three factors that make up Virchow’s triad in the pathogenesis of thrombosis?
Endothelial injury
Hypercoagulability
Abnormal blood flow
Describe the role of endothelial injury in the pathogenesis of thrombosis
Important in the formation of thrombi in
• Heart and Arteries
Examples of thrombi developed in:
• Left ventricle at sites of myocardial infarction
• On ulcerated plaques in advanced atherosclerosis
• Injured endocardium (cardiac surgery, myocarditis)
• Valves with inflammatory valve disease, and prosthetic valves
What are potential bases of endothelial injury other than MI, plaques, physical injury or inflammatory valve disease?
- Radiation injury
- Chemical agents: exogenous and endogenous
- Bacterial toxins or endotoxins
- Immunologic injuries
- Neoplastic involvement
What are the platelets role in the pathogenesis of thrombosis?
After injury to a vessel, platelets undergo three important reactions:
– Adhesion
– Secretion (release reaction)
– Aggregation (Platelet activation)
Describe the formation of a thrombus due to endothelial injury in 4 steps
A. Vasoconstriction due to reflex as endothelia released at site of injury
B. Primary hemostasis
C. Secondary hemostasis
D. Thrombus and antithrombotic events
What occurs in primary hemostasis?
- Platelet adhesion to damaged basement membrane with vWF present
- Shape change to fit more smoothly with artery wall
- Granule release (ADP, TXA2)
- Recruitment of more platelets
- Aggregation (hemostatic plug formed on collagen)
What annoying abbreviations are present in primary hemostasis?
ADP = Adenosine diphosphate vWF = von Willebrand factor TXA2 = Thromboxane A2 Pf4 = Platelet factor 4
What is a deficiency in von Willebrand’s factor called?
von Willerbrand’s disease
What does a deficiency in glycoprotein Ib cause?
Bernard-soulier syndrome
What does a deficiency in glycoprotein Ib -IIIa complex cause?
Glanzmann’s thrombasthenia
What occurs in secondary hemostasis?
1 Tissue factor is released from artery wall
2 Phospholipid complex expression occurs in platelets
3 Thrombin activated
4 Thus Fibrin polymerisation occurs which binds platelets with fibrin
What occurs in thrombus and antithrombotic events?
Release of
t-PA (fibrinolysis)
Thrombomodulin (blocks coagulation cascade)
Now within the forming thrombus there can be trapped neutrophils and blood cells
It is surrounded by polymerised fibrin
How do alterations to normal blood flow play a role in the pathogenesis of thrombosis?
Turbulence contributes to the development of
• Arterial and cardiac thrombi
Stasis contributes to
• Venous thrombosis
What do turbulence and stasis of blood flow do?
– Disrupt laminar flow
– Prevent the dilution of coagulation factors
– Retard the inflow of inhibitors of clotting factors
– Promote endothelial cell activation
Define hypercoagulability
• Can be defined as an alternation of the blood coagulation mechanism that in some way predisposes thrombosis.
What are the two types of hypercoagulability in the pathogenesis of thrombosis?
Primary (genetic)
Secondary (acquired)
What role does hyper coagulability play in the pathogenesis of thrombosis?
• Primary (genetic)
» Mutation in the factor V gene = Leiden mutation » Antithrombin III deficiency
» Protein C and S deficinecy
• Secondary (acquired):
» High risk: bed rest (immobilisation). MI, Tissue damage, CA,
prosthetic valves, DIC
» Lower risk: AF, cardiomyopathy, nephrotic syndrome, oral contraceptive, sickle cell anaemia, smoking
Where may thrombi occur?
Thrombi may occur anywhere in the cardiovascular system.
What are the three types of morphology of thrombi?
- Mural thrombi
- Arterial thrombi
- Venous thrombosis (phlebothrombosis)
What is a mural thrombi?
– Applied to one wall of underlying structure, occur in the capacious lumina of the heart chambers and aorta
What is an arterial thrombi?
• Usuallyocclusive • Maybemural • Frequentinthese arteries: – Coronary – Cerebral – Femoral • Grey-white and friable
What is a venous thrombi?
(phlebothrombosis)
• Invariably occlusive and dark red
• Affect the veins of the lower extremities (90%):
– Deep calf, femoral, popliteal, iliac veins
NB. Thrombophlebitis=
– Inflamed + thrombosed
What can you expect to see in the histological appearance of a thrombus?
Pale band of fibrin+platelets
Red band of RBC
Note laminations called lines of Zahn
What are the possible fates of a thrombus in the veins?
It may undergo:
Propagation towards the heart
Embolisation to the lungs
organisation and become recanalised (canals form in thrombus)
This may lead to organisation and incorporation into the wall
Or it may resolve
What are the clinical correlations of the thrombi?
- They cause obstruction of arteries and veins
* They provide possible sources of emboli
What are the symptoms of arterial thrombosis?
Arterial thrombosis:
• Loss of Pulses distal to the thrombus
• Area becomes Perishing cold, Pale, Painful, Paraesthesia
• Eventually tissue dies and gangrene results
What may occur due to loss of blood in a vessel?
Auto-amputation due to gangrene
What are the symptoms of venous thrombosis (phlebothrombosis)?
– Superficial (saphenous system)
– Congestion, swelling, pain, tenderness (rarely
embolise) – Deep
– Foot and ankle oedema, Homans’ sign
– Could be asymptomatic and recognised only when they have embolised
What are the treatments available for thrombosis?
- Stockings(prevention, esp on planes)
- Anticoagulant drugs.These aim to prevent the clot growing any larger and to prevent or stop an embolism.
- Currently there are two main forms of anticoagulant drugs: heparin (i.v or s.c) and warfarin (orally).
What is the definition of an embolism?
- An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin.
- 99% of all emboli arise in thrombi (thromboembolism).
- Unless otherwise qualified, the term embolus implies thromboembolism.
What do rare forms of embolism contain?
– Bone or bone marrow – Atheromatous debris – Droplets of fat – Bits of tumour – Foreign bodies (such as bullets) – Bubbles of air or nitrogen
What are the different classifications of embolism?
- Pulmonary embolism
- Systemic embolism
- Amniotic fluid embolism
- Air embolism
- Fat embolism
What is a pulmonary embolism?
• Occlusion of a large or medium-sized pulmonary artery is embolic in origin until proved otherwise.
– Major clinical problem among hospitalised patients
• More than 95% of all pulmonary emboli arise in thrombi within the large deep veins of the lower leg.
Where can you find the emboli of a pulmonary embolism?
• Large emboli may impact in the main pulmonary artery or lodge at the bifurcation as a saddle embolus.
What are the two main pathophysiologic consequences of a pulmonary embolism?
– Respiratory compromise
– Haemodynamic compromise
• A large PE is one of the few causes of virtually instantaneous death
– “Pulseless Electrical Activity PEA”
What may a smaller pulmonary emboli cause?
– Acute respiratory and cardiac problems.
• Chest pain, dyspnoea, shock, increased LDH, haemoptysis.
• Chest x-ray may disclose a pulmonary infarct as a wedge-shaped infiltrate.
• Emboli can also be detected by pulmonary lung scanning using radionuclides.
• Occlusion puts some strain on the heart which is evident on the ECG.
What is a systemic embolism?
- This term refers to emboli that travel through the arterial circulation.
- 80-85% arise from thrombi within heart.
• Less common sources include thrombi developing in relation to: – Ulcerated atherosclerotic plaque. – Aortic aneurysms. – Infective endocarditis. – valvular or aortic prostheses.
Where may a systemic embolism cause issue?
• Arterial emboli almost always cause infarction
• Major sites of lodgement of all systemic emboli are:
– Lower extremities (70-75%)
– The brain (10%)
– Viscera (mesenteric, renal, splenic) (10%)
– Upper limbs (7-8%)
What is an air embolism?
• The presence of bubbles of air or gas within the circulation obstruct vascular flow and damage tissues just as thrombotic masses.
– The injury is now referred as barotrauma.
What is the pathophysiology of an air embolism?
– Delivery or abortion
– The performance of pneumothorax
– Injury to the lung or the chest wall
– Caisson disease or decompression sickness
What is Caisson disease?
• Caisson disease
– Scuba and deep sea divers
– Workers engaged in underwater tunnelling
• If the individual decompresses too rapidly, helium and nitrogen tend to persist to form gaseous emboli within blood vessels and tissues
• Acute form
– commonly known as “the bends” or “the chokes”
• Chronic Form
– is more properly referred to as
caisson disease
• Treatment:
– recompression chamber
What is a fat embolism?
• Minute globules of fat can often be demonstrated in the circulation following
– Fractures of the shafts of long bones
– And rarely, with soft tissue trauma and burns
• Only 1% of individuals with severe skeletal injury manifest clinical signs known as
– Fat embolism syndrome
Describe the pathogenesis of a fat embolism
• The pathogenesis of this symptom complex involve both:
– Mechanical obstruction
– microagregates of neutral fat cause occlusion
– Chemicalinjury
– free fatty acids released from fat globules result in
toxic injury to the vascular endothelium
• The microscopic demonstration of fat globules requires special techniques using frozen sections and fat stains.
What are the symptoms of a fat embolism?
• Clinically it is characterised by:
– Pulmonary insufficiency
– Neurologic symptoms
– Anaemia and thrombocytopenia
– The symptoms appear after latent 24-72h period
• Sudden onset of tachypnoea, dyspnoea and tachycardia
• Neurologic symptoms include irritability and restlessness which progress to delirium and coma.
What is an amniotic fluid embolism?
• Is a rare complication of labour and one of cause of maternal mortality (86%).
• The cause is the infusion of amniotic fluid into the maternal circulation.
• Morphology:
– Victim’s pulmonary microcirculation at post- mortem examination contain:
– Epithelial squames from foetal skin, lanugo hair, fat from vernix caseosa, mucin from foetal respiratory or GI tract.
What are the symptoms of amniotic fluid embolism?
• The clinical presentation: – Profound respiratory difficulty • With deep cyanosis and cardiovascular shock – Followed by convulsions and – Profound coma
What is the definition of infarction?
• Infarct (lat. infarcire = to stuff).
– Is an area of ischaemic necrosis caused by occlusion of arterial supply or venous drainage in a particular tissue.
What is the definition of necrosis?
• Necrosis (Greek nekro = dead).
– Refers to a spectrum of morphological changes that follow cell death in living tissue, largely resulting from the progressive action of enzymes on the lethally injured cells.
What are the causes of 99% of infarctions?
- Thrombosis
* Embolism
What are causes of infarct other than thrombosis and embolism?
- Vasospasm
- Expansion of atheroma
- Compression of a vessel
- Twisting of the vessels
- Traumatic rupture
What factors influence ht development of an infarct?
• Nature of the vascular supply
- • Liver, hand, intestines = dual blood supply
- • Kidneys and spleen = single
• Rate of development of occlusion
-• Heart
• Vulnerability to hypoxia
-• Neurons 3-4min, Myocardial cells 20-30min, Fibroblasts many hours
• Oxygen content of blood
-• Anaemic or cyanotic patients
What are the types of infarcts?
- Red (haemorrhagic)
- White (anaemic)
- Septic or bland
Where do red (haemorrhagic) infarcts occur?
- Venous occlusions
- In loose tissues
- In tissues with dual circulation
Where do white (anaemic) infarcts occur?
- Arterial occlusions
* Solid organs
What is the timescale of the histology of infarction?
• Ischaemic coagulative necrosis (min - days)
– Liquefactive necrosis in the CNS
• Inflammatory response (hours - 7 days)
• Reparative response (1 - 2 weeks)
• Scarring (2 weeks - 2 months)
