Pathology chapters
Thrombosis and embolism
Why blood clots inside living vessels (Virchow's triad), how a thrombus differs from a post-mortem clot, what happens to a thrombus, and the types of emboli (thrombo-, fat, air, amniotic fluid) with their effects.
- A thrombus is a solid mass of blood constituents formed inside a living vessel or heart; Virchow's triad: endothelial injury, abnormal blood flow (stasis or turbulence) and hypercoagulability.
- Thrombi show lines of Zahn (layers of platelets/fibrin and red cells) and are attached to the wall; post-mortem clots are rubbery, unattached, with "chicken fat" and "current jelly" parts.
- An embolus is a detached mass carried by blood to a distant site; over 95% of pulmonary emboli arise from deep leg veins; others are fat (long-bone fractures), air, amniotic fluid and tumour.
On this page
Overview
Haemostasis keeps blood fluid in normal vessels but forms a clot quickly at a site of injury. Thrombosis is haemostasis in the wrong place: a thrombus is a solid mass made from blood constituents (platelets, fibrin, red and white cells) formed inside the vessels or heart of a living person.
An embolus is a detached solid, liquid or gaseous mass carried by the blood to a site distant from its origin. Most emboli are pieces of thrombus (thromboembolism).
Virchow's triad
| Factor | Mechanism | Examples |
|---|---|---|
| Endothelial injury | Exposes collagen and tissue factor; loses anticoagulant surface | Myocardial infarction (mural thrombus), atherosclerotic plaque, vasculitis, valve injury (endocarditis), hypertension, smoking |
| Abnormal blood flow | Turbulence damages endothelium; stasis lets platelets touch the wall and stops dilution of clotting factors | Stasis: immobility, heart failure, atrial fibrillation (left atrial thrombus), aneurysms, varicose veins, hyperviscosity (polycythaemia). Turbulence: plaques, bifurcations |
| Hypercoagulability | Higher tendency to clot | See table below |
Endothelial injury is the dominant factor in the heart and arteries; stasis is the dominant factor in veins. Endothelial injury alone can cause thrombosis.
Causes of hypercoagulability
| Primary (inherited) | Secondary (acquired) |
|---|---|
| Factor V Leiden (the commonest; factor V resists inactivation by activated protein C) | Prolonged immobilisation, bed rest |
| Prothrombin gene mutation (G20210A) | Surgery, fractures, burns |
| Antithrombin III deficiency | Cancer (Trousseau syndrome: migratory thrombophlebitis) |
| Protein C or protein S deficiency | Pregnancy and the post-partum period; oral contraceptives |
| Hyperhomocysteinaemia | Antiphospholipid syndrome; heparin-induced thrombocytopenia; nephrotic syndrome; smoking, obesity, old age |
Antiphospholipid syndrome prolongs the APTT in the laboratory (lupus anticoagulant) but causes thrombosis (and recurrent miscarriage) in the patient, not bleeding.
Morphology of thrombi
- Arterial and cardiac thrombi start at sites of endothelial injury or turbulence; they are pale, platelet-rich and grow backwards (retrograde) from the attachment point. Arterial thrombi are usually occlusive in medium arteries (coronary, cerebral, femoral).
- Mural thrombi are attached to the wall of a heart chamber or of the aorta (after myocardial infarction, in a dilated left atrium in AF, in aneurysms).
- Venous thrombi (phlebothrombosis) form in slow flow; they are red ("red thrombi"), rich in red cells and fibrin, and grow in the direction of flow towards the heart. About 90% involve the deep veins of the legs.
- Vegetations are thrombi on heart valves: infective endocarditis (bacteria), non-bacterial thrombotic endocarditis (cancer, hypercoagulable states) and Libman-Sacks endocarditis (lupus).
Lines of Zahn: alternating pale layers (platelets and fibrin) and darker layers (red cells). They form only in flowing blood, so they show the thrombus formed before death.
Thrombus vs post-mortem clot
| Feature | Thrombus (ante-mortem) | Post-mortem clot |
|---|---|---|
| Attachment | Attached to the vessel wall | Not attached; slips out |
| Consistency | Dry, firm, friable | Soft, rubbery, gelatinous |
| Lines of Zahn | Present | Absent |
| Colour | Grey-red, layered | Dark red lower part ("current jelly") and yellow upper part ("chicken fat") from red cells settling |
| Shape | Not a cast of the vessel | Cast of the vessel |
Lines of Zahn and attachment to the wall = ante-mortem thrombus. "Chicken fat" and "current jelly" = post-mortem clot.
Fate of a thrombus
- Propagation: grows and may block the vessel.
- Embolisation: part or all of it breaks off.
- Dissolution: removed by fibrinolysis (mainly fresh thrombi; the basis of thrombolytic therapy, which works best within hours).
- Organisation and recanalisation: older thrombi are invaded by granulation tissue (capillaries, fibroblasts); new channels form through it and may partly restore flow.
- Rarely, infection of the thrombus (septic thrombus, mycotic aneurysm).
Consequences of thrombosis
- Arterial: ischaemia and infarction (heart, brain, gut, limbs); embolism.
- Venous: congestion and oedema of the area drained (swollen, painful leg), pulmonary embolism. Superficial leg vein thrombi rarely embolise but cause local pain and varicose ulcers.
Embolism
Pulmonary thromboembolism
- More than 95% arise from deep veins of the leg (popliteal, femoral, iliac).
- Most are clinically silent (small), organising into the vessel wall.
- Large emboli blocking 60% or more of the pulmonary circulation, or lodging at the bifurcation of the pulmonary trunk (saddle embolus), cause sudden death, acute right heart failure (cor pulmonale) or cardiovascular collapse.
- Medium-sized arteries: haemorrhage, or infarction if the bronchial circulation is already poor (as in heart failure).
- Many small emboli over time: pulmonary hypertension.
Paradoxical embolism: a venous embolus passes through an atrial or ventricular septal defect or patent foramen ovale into the systemic circulation (for example, causing a stroke).
Systemic thromboembolism
Emboli in arterial blood. About 80% come from intracardiac mural thrombi (left ventricular infarcts, left atrial thrombus in atrial fibrillation, dilated left ventricle); others from aortic aneurysms, plaques and valve vegetations.
Main destinations: lower limbs (most), brain, intestines, kidneys and spleen. The result is usually infarction.
Other emboli
| Type | Cause | Features |
|---|---|---|
| Fat embolism | Fractures of long bones (femur), soft tissue crush, burns | Fat embolism syndrome in a minority, typically 1–3 days after injury: respiratory distress (hypoxia), neurological signs (confusion), petechial rash, anaemia and thrombocytopenia |
| Air (gas) embolism | Obstetric or chest procedures, neck vein injury, IV lines | Usually more than about 100 mL is needed to cause symptoms; bubbles obstruct flow |
| Decompression sickness ("caisson disease") | Rapid ascent in divers; flying unpressurised | Nitrogen bubbles: the bends (joint and muscle pain), the chokes (lungs); chronic form: avascular necrosis of femoral head |
| Amniotic fluid embolism | Labour or just after delivery; tear in placental membranes | Rare but high mortality; sudden breathlessness, cyanosis, shock, seizures, then DIC; squamous cells, lanugo hair and mucin in the maternal pulmonary vessels |
| Tumour, septic, foreign body, atheromatous (cholesterol) emboli | Tumour spread; infected vegetations; IV drug use; plaque manipulation | Metastasis; abscesses; granulomas; renal and skin infarcts |
Fat embolism follows long-bone fracture with hypoxia, confusion and petechiae after a delay of 1–3 days. Amniotic fluid embolism causes collapse and DIC during or after labour.
Expect: Virchow's triad and examples, the commonest inherited hypercoagulable state, lines of Zahn, thrombus vs post-mortem clot, arterial vs venous thrombi, fate of a thrombus, source of pulmonary emboli and saddle embolus, paradoxical embolism, source of systemic emboli, and fat, air, decompression and amniotic fluid embolism.
Quick revision
- Virchow's triad: endothelial injury, abnormal flow, hypercoagulability.
- Arteries: endothelial injury dominates; veins: stasis.
- Factor V Leiden: commonest inherited cause.
- Lines of Zahn and wall attachment: ante-mortem thrombus.
- Fate: propagation, embolisation, dissolution, organisation and recanalisation.
- Pulmonary emboli: deep leg veins; saddle embolus: sudden death.
- Systemic emboli: mostly from mural thrombi in the heart.
- Fat embolism: long-bone fracture, 1–3 days, hypoxia, confusion, petechiae.
Written by The House Job from standard pathology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
What is Virchow's triad?
The three main factors that lead to thrombosis: endothelial injury, abnormal blood flow (stasis or turbulence) and hypercoagulability.
How is a thrombus different from a post-mortem clot?
A thrombus is attached to the vessel wall, firm and friable, and shows lines of Zahn; a post-mortem clot is unattached, rubbery and has "current jelly" and "chicken fat" parts.
Where do most pulmonary emboli come from?
From thrombi in the deep veins of the legs.
What is a paradoxical embolus?
A venous embolus that crosses into the arterial circulation through a defect in the heart such as a patent foramen ovale.