Paper I
Question
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- (a) Discuss the primary abnormalities that lead to thrombosis (Virchows triad) ( 8 mark(s)
- (b) Describe the morphology of a thrombus. ( 3 mark(s)
- (c) What is the fate of a thrombus. 4 mark(s)
Answer
(a) Virchow’s triad — primary abnormalities leading to thrombosis
1. Endothelial injury
- Damaged endothelium exposes subendothelial collagen and tissue factor, promotes platelet adhesion/activation, and loses its normal antithrombotic surface properties (prostacyclin, NO, thrombomodulin)
- Examples: myocardial infarction (mural thrombus over infarcted endocardium), vasculitis, atherosclerotic ulceration, hypertension, toxins (cigarette smoke)
2. Abnormal blood flow
- Stasis: Prevents dilution of activated clotting factors, allows platelet accumulation near the vessel wall, and promotes endothelial activation
- Examples: atrial fibrillation, prolonged immobilization/bed rest, aneurysms
- Turbulence: Causes endothelial injury/dysfunction and forms local countercurrents/stasis pockets
- Examples: arterial bifurcations, over atherosclerotic plaques
3. Hypercoagulability
- Primary (genetic): Factor V Leiden mutation, prothrombin gene mutation, protein C/S or antithrombin III deficiency
- Secondary (acquired): Malignancy, pregnancy/oral contraceptives, nephrotic syndrome, prolonged immobilization, antiphospholipid antibody syndrome, smoking
(b) Morphology of a thrombus
- Composed of alternating pale layers of platelets/fibrin and darker layers of red cells — lines of Zahn, a feature that helps distinguish an antemortem thrombus from a postmortem clot (which lacks lines of Zahn)
- Arterial (mural) thrombi: Typically occur at sites of turbulence/endothelial injury (e.g., over atherosclerotic plaques), tend to grow retrograde from the point of attachment, greyish-white and firmly attached
- Venous thrombi: Occur at sites of stasis, tend to propagate in the direction of blood flow, more red cell-rich (red/coagulation thrombi), less firmly attached, higher embolic potential
- Vegetations: Thrombi on heart valves (infective or non-infective)
(c) Fate of a thrombus
- Propagation: The thrombus enlarges through further accumulation of platelets and fibrin, potentially leading to vessel occlusion
- Embolization: Part or all of the thrombus dislodges and travels through the bloodstream, lodging elsewhere (e.g., pulmonary embolism from a deep venous thrombus)
- Dissolution (resolution): The thrombus is removed by fibrinolytic activity, especially if recent/fresh
- Organization and recanalization: Ingrowth of endothelial cells, smooth muscle cells, and fibroblasts into the thrombus, eventually forming new capillary channels that re-establish some degree of blood flow through the previously occluded vessel