Thrombosis/Embolism/Infarction

Question 1

Describe how Virchow’s triad explains thrombosis

Answer 1

Virchow’s triad
- Endothelial injury can cause abnormal blood flow - -
- Abnormal blood flow can damage endothelium or make clotting easier.
- Hypercoagulability increases the chance of clotting when either of the other two happen.

1. Endothelial injury
   - Severe endothelial injury exposes:
   - vWF - primary hemostasis - platelet plug
   - TF - secondary hemostasis - coagulation cascade
2. Abnormal blood flow
   - prevents laminar flow
   - Turbulence (chaotic blood flow - too fast - can injure endothelium)
   - Stasis (no flow/too slow) - clotting factor buildup
3. Coagulation
   - Abnormally high tendency of the blood to clot

Primary (genetic) disorders
* Point mutations in the factor V gene (Factor V Leiden) and prothrombin gene

Secondary (acquired) disorders
* Prolonged bed rest or immobilisation
* Myocardial infarction
* Atria fibrillation
* Tissue injury (surgery, fracture, burn)
* Cancer (release of procoagulants)
* Prosthetic cardiac valves
* Disseminated intravascular coagulation
* Heparin-induced thrombocytopenia
* Antiphospholipid antibody syndrome

Question 2

Explain how the features of the circularity system (veins, arteries and heart) affect Virchow’s triad

Question 3

Understand the fate of thrombi and lines of ZAHN

Answer 3

• Thrombus = solid mass of blood constituents formed within intact, flowing vascular system
  o Pathological extension of normal haemostasis

Lines of ZAHN - only in strong blood flow areas (arteries) (less prominent in slow blood flow areas)
- Pale (fibrin/platelet)
- Dark (RBC)
Don’t get lines of ZAHN after post-mortem

Fate of thrombi
1. Propagation (growth)
- Accumulation of additional platelets and fibrin
- Vessel obstruction

2. Embolization
   - Thrombi dislodge/fragment and are transported elsewhere
3. Dissolution (fibrinolysis)
   - Recent thrombi can be broken down/removed
   - Older thrombi are more resistant b/c extensive fibrin polymerisation
4. Organisation & recanalization
   - Older thrombi induce inflammation and fibrosis
   - Endothelial cells, smooth muscle cells and fibroblasts grow into organising thrombus
   - New capillary channels
   - Vascularised mass can be incorporated into the vessel wall (subendothelial swelling)

Question 4

Describe the outcome of thrombosis in veins, arteries and the heart

Answer 4

1. Veins:
   - o Low pressure
   o Valve and muscle pressure for venous return
   o No atheroma
   o Begins at sites of stasis
    Especially valves
   o Almost always occlusive
   o Red/stasis thrombi (RBC)
   o Most often in lower extremities
   o Occurs in:
    Superficial veins
   * Lie just below the skin
   * Carry blood from the skin and outer tissues to deep veins
    Superficial vein thrombi:
   * Congestion, swelling, pain and tenderness
   * Rarely embolise
   * Can lead to skin infection and varicose ulcers b/c impaired drainage
    Deep veins
   * Found within muscle
   * Receive blood from the superficial veins and pump it to the heart
    Deep vein thrombi (DVT):
   * Larger veins at or above knee joint
   * Can embolise to pulmomary artery or deeper into lungs
   * Asymptomatic in 50% individuals b/c collateral circulation develops
   * Associated with hypercoagulable states:
   o Cardiac failure, surgery, trauma, burns, late pregnancy, post-partum, cancer, advanced age, bedrest, immobilisation (flying)
2. Arteries:
   > Arterial
   - High blood pressure
   - Fast blood flow
   - Shear stress
   - Atheroma (Atheromatous plaque, is a build up of fatty material in the arteries)

> Arterial thrombosis
- Begin at sites of turbulence
- Frequently occlusive
- Grow opposite direction of blood flow – towards heart
- Atherosclerosis (Loss of endothelial integrity and abnormal vascular flow)
- Local ischemia (hypoxia) (Obstruction/occlusion of vessels)
- Infarction (cell death) (Brain, kidney, spleen)

3. Heart:
   - Mural thrombi
   o Heart chambers
    Abnormal heart contraction
   o Aortic arch
    Ulcerated atherosclerotic plaque and aneurysmal dilation
   o Mitral valves
    Vegetations (mitral valve thrombi)
    Infectious or sterile origin

Question 5

Describe the clinical consequences of emboli in the pulmonary and systemic circulation

Answer 5

Systemic (thrombo)embolism
o Most systemic emboli (80%) arise from intracardiac mural thrombi
o Remaining (20%)
 Aortic aneurysms
 Atherosclerotic plaques
 Valvular vegetations
 Or venous thrombi (paradoxical emboli)
o Most lower extremities (75%) or the brain (10%)
o Other including the intestine, kidneys, spleen, and upper extremities, may be involved
- Pulmonary embolism
o Most (90%) originate from DVT
o Clinically silent
o Sudden death
 Obstruction of >60% of pulmonary circulation
o Haemorrhage or infarction
 Obstruction of medium or small end arteries
o Hypertension/right sided heart failure
 Multiple small emboli over time

Question 6

Understand the factors that determine the consequences of ischemia (reversible versus irreversible/infarction injury)

Question 7

Apply your understanding of adaptation and injury to a disease caused by ischemia (MI)