Thrombosis and atherosclerosis
Haemostasis, thrombosis, embolism, atherosclerosis, hypertension and aneurysm
Haemostasis and vascular disease for FCPS Part 1: clotting, platelet disorders, thrombosis, emboli, atherosclerosis, hypertension, aneurysm and dissection. Each is linked to Doppler, CT angiography and plain film findings.
Normal haemostasis and its brakes
- Primary: platelets adhere via von Willebrand factor to GP Ib (the first step after injury), are activated (ADP, thromboxane A2) and aggregate via fibrinogen on GP IIb/IIIa; Glanzmann thrombasthenia lacks IIb/IIIa.
- Secondary: tissue factor starts the cascade; thrombin converts fibrinogen into fibrin and activates platelets and factor XIII. Factors II, VII, IX and X need vitamin K. In cirrhosis the liver cannot make factors, so fresh frozen plasma (with platelets if low) corrects coagulopathy before surgery; vitamin K alone does not.
- Topical thrombin injected into a femoral pseudoaneurysm sac clots it in seconds by turning fibrinogen directly into fibrin (risk of distal thrombosis if the neck is wide).
- Brakes: antithrombin (amplified by heparin) and protein C/S, activated when thrombin binds endothelial thrombomodulin; endothelium also makes prostacyclin and nitric oxide.
Platelet disorders
| Condition | Mechanism | Clue |
|---|---|---|
| Immune thrombocytopenic purpura | IgG against GP IIb/IIIa; splenic macrophages remove platelets (type II) | Child, petechiae 2 weeks after a viral illness, isolated very low platelets, rest of count normal |
| Thrombotic thrombocytopenic purpura | Low ADAMTS13 leaves ultra-large vWF multimers; platelet microthrombi | Fever, confusion, renal impairment, schistocytes, low platelets, normal PT and APTT; plasma exchange |
| Haemolytic uraemic syndrome | Shiga toxin (E. coli O157) damages glomerular endothelium | Child after bloody diarrhoea, renal failure |
| DIC | Widespread tissue factor (sepsis, amniotic fluid, abruption) | Long PT and APTT, low fibrinogen, high D-dimer |
| HIT | IgG to heparin–platelet factor 4 activates platelets | Day 5–10, low platelets plus new clot |
Thrombophilia
| Condition | Mechanism | Clue |
|---|---|---|
| Factor V Leiden | Factor Va resists activated protein C | Commonest inherited thrombophilia |
| Prothrombin G20210A | G-to-A change in the 3' untranslated region raises the plasma prothrombin level; function is normal | Second commonest inherited |
| Antithrombin deficiency | Heparin cannot work; lost in nephrotic urine | Heparin resistance |
| Antiphospholipid syndrome | Antibody to phospholipid-binding proteins | Commonest acquired thrombophilia; long APTT yet clots; lupus anticoagulant predicts risk best |
| Cancer | Tumour tissue factor | Pancreas, mucinous tumours |
Thrombus, clot and embolus
- Virchow's triad: endothelial injury (dominant in arteries), stasis (dominant in veins), hypercoagulability.
- Arterial and coronary thrombus: pale grey, granular, made mainly of platelet aggregates bound by fibrin, with lines of Zahn (formed in flowing blood). Venous thrombus: dark red, gelatinous, red cells trapped in fibrin; starts behind valve cusps in the calf.
- Postmortem clot: unattached, currant-jelly and chicken-fat layers.
- Fate of a thrombus: propagation, embolism, lysis, or organisation: granulation tissue grows in and new channels form (recanalisation), partly restoring flow.
- DVT on ultrasound: the vein does not collapse under probe pressure.
- Where emboli lodge: venous emboli (from deep leg veins, the commonest source) pass through the right heart and lodge in the pulmonary arteries. Arterial emboli come mostly from a left atrial (AF) or left ventricular (post-MI) mural thrombus and lodge in the legs, brain, gut and kidneys.
- Pulmonary embolism on X-ray: often normal; a hyperlucent zone with sparse vessels beyond the clot (Westermark sign) shows reduced perfusion beyond the embolus, sometimes with an enlarged hilar artery.
- Acute mesenteric ischaemia: an atherosclerotic SMA thrombosis (or embolism) makes the small bowel dark purple: haemorrhagic (wet) infarction; pain is out of proportion to signs.
- Embolic arterial occlusion shows a sharp meniscus cut-off with few collaterals; thrombosis on atheroma has collaterals.
Special emboli
| Type | Setting | Key point |
|---|---|---|
| Fat | Long-bone fracture, day 1–3 | Confusion, hypoxia, petechiae; demonstrated by Oil red O or Sudan stain on frozen sections (processing dissolves fat) |
| Amniotic fluid | Labour | Sudden collapse, then DIC; high mortality |
| Air | Neck vein cannulation, trauma | About 100 mL entering rapidly can be fatal (froth in the right ventricle) |
| Cholesterol crystal | After angiography | Purple toes with good pulses, eosinophilia, renal failure |
| Paradoxical | Patent foramen ovale | Venous clot reaches systemic arteries |
Atherosclerosis
- A disease of the intima of large and medium arteries. Starts with endothelial dysfunction (smoking, hypertension, LDL, diabetes). Oxidised LDL enters macrophages via scavenger receptors, forming foam cells. The fatty streak is the earliest lesion.
- Medial smooth muscle cells migrate into the intima and make the fibrous cap. Thin caps rupture (acute coronary syndromes).
- Commonest and worst site: abdominal aorta (below the renals), then coronaries, popliteal, internal carotid. Plaques favour low, oscillating shear stress.
- An infarcted myocardium shows coagulative necrosis: by 3 days nuclei are lost but cell outlines remain.
- Doppler below a stenosis turns from triphasic to damped monophasic.
Hypertension and its vessels
- In essential hypertension the raised afterload increases cardiac workload, so the left ventricle undergoes concentric hypertrophy; oxygen demand rises.
- Secondary causes to recognise: coarctation of the aorta (young adult, radiofemoral delay, rib notching); Conn syndrome (hypertension, high sodium, low potassium, low renin); renal artery stenosis; phaeochromocytoma; Cushing syndrome.
- After a thiazide alone fails, add an ACE inhibitor (or ARB) or a calcium channel blocker.
| Lesion | Seen in | Result |
|---|---|---|
| Hyaline arteriolosclerosis | Benign hypertension, diabetes | Small granular kidneys |
| Hyperplastic (onion-skin) arteriolosclerosis | Malignant hypertension | Fibrinoid necrosis, rapid renal failure |
| Charcot–Bouchard microaneurysms | Lenticulostriate arterioles | Deep brain haemorrhage |
Aneurysm, dissection and AV fistula
- Berry aneurysm: at circle of Willis branch points where the vessel wall lacks tunica media; rupture with a sudden rise in pressure causes subarachnoid haemorrhage (ADPKD).
- Abdominal aortic aneurysm: matrix metalloproteinases destroy medial elastin; wall tension rises with radius (Laplace). Mural thrombus can make the angiogram look normal.
- Pseudoaneurysm after femoral puncture: yin-yang flow through a narrow neck. Mycotic aneurysm: septic emboli.
- Aortic dissection: hypertension is the commonest cause (also Marfan, cystic medial degeneration). Blood enters through an intimal tear and the false lumen runs within the outer part of the tunica media, so the flap carries intima and inner media. Stanford A involves the ascending aorta.
- Traumatic arteriovenous fistula (after a stab wound): continuous machinery bruit, dilated veins, bounding pulse; duplex shows high-velocity, low-resistance arterial flow above it and pulsatile arterial-type flow in the vein. A large one causes high-output heart failure.
Vasculitis and veins
| Disease | Key point |
|---|---|
| Thromboangiitis obliterans | Young male smokers; digital gangrene |
| Polyarteritis nodosa | Hepatitis B; microaneurysms; spares lungs |
| Giant cell arteritis | Doppler halo of wall oedema; biopsy shows granulomatous inflammation fragmenting the internal elastic lamina with giant cells; skip lesions |
| Kawasaki disease | Child; coronary aneurysms |
- May–Thurner: right common iliac artery compresses the left common iliac vein. Isolated gastric varices: splenic vein thrombosis.
Remember Arteries clot white on damaged walls; veins clot red where blood stands still.
Exam trap A long APTT in antiphospholipid syndrome is a laboratory effect; the patient's real tendency is to clot, not bleed.
Exam trap TTP has low platelets and schistocytes with normal PT and APTT; DIC prolongs both.
How FCPS asks about this
- First step of primary haemostasis: platelet adhesion via vWF to GP Ib.
- Fever, confusion, schistocytes, low platelets, normal clotting: TTP (low ADAMTS13).
- Isolated low platelets two weeks after a virus: ITP.
- Pale granular coronary thrombus: platelet aggregates bound by fibrin.
- Where a deep vein embolus lodges: pulmonary arteries.
- Layer containing the false lumen in dissection: outer tunica media.
- Young hypertensive with radiofemoral delay: coarctation of the aorta.
Test yourself on this topic
5 of the 131 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 62-year-old man with a pancreatic body mass and liver metastases also has bilateral pulmonary emboli. Which mechanism mainly explains his thrombosis?
Answer: Tumour cells expressing tissue factor
Many cancers, especially mucin-secreting adenocarcinomas of the pancreas, stomach and lung, are strongly prothrombotic. Tumour cells express tissue factor and release tissue factor-bearing microparticles and mucins that activate the extrinsic pathway and platelets. Stasis from immobility and venous compression adds to this. The result may be DVT and PE, or migratory superficial thrombophlebitis (Trousseau sign). Urinary antithrombin loss occurs in nephrotic syndrome, and PF4 antibodies occur after heparin.
Cancer and clotting
- Mucinous adenocarcinomas (pancreas)
- Tumour tissue factor and microparticles
- Plus stasis and compression
- Trousseau: migratory thrombophlebitis
Remember Unexplained clots in an older adult: look for a hidden adenocarcinoma.
Exam trap A normal thrombophilia screen does not exclude a cancer-driven clotting tendency.
Why the other options are wrong
- Loss of antithrombin in the urine A mechanism of thrombosis in nephrotic syndrome.
- Antibodies against platelet factor 4 The cause of heparin-induced thrombocytopenia.
- Failure of vitamin K absorption Would cause bleeding, not clotting.
- A mutation in the factor V gene An inherited thrombophilia not linked to cancer.
During removal of a central venous catheter from a sitting patient, air is sucked into the jugular vein. Roughly what volume of air entering the venous circulation is generally needed before it causes serious clinical effects?
Answer: More than about 100 mL
Small amounts of air entering the veins are absorbed and cause no harm. Larger volumes, generally more than about 100 mL entering rapidly, coalesce into frothy bubbles that collect in the right ventricle and pulmonary outflow tract, blocking blood flow (an 'air lock'), and also obstruct small pulmonary vessels. The result is sudden breathlessness, hypotension and collapse. Risk is highest when the insertion site is above the heart, so central lines are inserted and removed with the patient head-down.
Air embolism
- Clinical effect usually over 100 mL
- Froth blocks right ventricular outflow
- Sudden collapse, hypotension
- Prevent: head-down for central lines
Remember A large, fast bolus of air locks the right heart.
Exam trap With a patent foramen ovale, even smaller volumes can cross into the arteries and cause a stroke.
Why the other options are wrong
- About 1 mL Tiny bubbles are absorbed without effect.
- About 10 mL Still too small to cause collapse in an adult.
- More than about 2 litres Far smaller volumes than this are already dangerous.
- Any volume, however small Small volumes are absorbed harmlessly; the effect depends on volume and speed.
A 27-year-old woman has a second DVT with no provoking cause. Factor V Leiden testing is negative, but she carries a G-to-A change in the 3' untranslated region of the prothrombin gene. How does this variant promote thrombosis?
Answer: It raises the plasma prothrombin level
The prothrombin G20210A variant lies in the 3' untranslated region, so the protein itself is normal. The change makes the messenger RNA more stable and more efficiently processed, so the liver makes more prothrombin, and plasma levels rise by about a third. More substrate means more thrombin generation and a higher risk of venous thrombosis. It is the second commonest inherited thrombophilia after factor V Leiden.
Prothrombin G20210A
- Variant in 3' untranslated region
- Protein is normal
- More prothrombin made
- 2nd commonest inherited thrombophilia
Remember Normal prothrombin, just too much of it.
Exam trap The mutation changes how much prothrombin is made, not how it works.
Why the other options are wrong
- It makes thrombin resistant to antithrombin The thrombin made is structurally normal and still inhibited by antithrombin.
- It blocks protein C activation by thrombin Protein C activation is unaffected.
- It lowers the plasma fibrinogen level Fibrinogen is not reduced; low fibrinogen would cause bleeding.
- It produces antibodies to phospholipid Antiphospholipid antibodies are acquired, not caused by this variant.
A 72-year-old woman has new temporal headache, jaw pain on chewing, a tender, pulseless temporal artery and an ESR of 95 mm/h. Temporal artery biopsy will most likely show:
Answer: Granulomatous inflammation fragmenting the elastic lamina
This is giant cell (temporal) arteritis. Histology shows granulomatous inflammation of the media centred on the internal elastic lamina, which is fragmented, with multinucleated giant cells, lymphocytes and macrophages, and intimal thickening that narrows the lumen. Involvement is segmental, so a normal biopsy does not exclude it. Fibrinoid necrosis with aneurysms suggests polyarteritis nodosa.
Giant cell arteritis
- Age over 50, high ESR
- Jaw claudication, headache
- Biopsy: granulomas, giant cells
- Broken internal elastic lamina
Remember Old woman, sore scalp, high ESR: think temporal arteritis.
Exam trap Skip lesions mean a short, negative biopsy does not exclude the disease.
Why the other options are wrong
- Fibrinoid necrosis with neutrophils and microaneurysms Typical of polyarteritis nodosa.
- Onion-skin hyperplasia of smooth muscle cells The arteriolar lesion of malignant hypertension.
- Segmental thrombosis with microabscesses in the clot Describes thromboangiitis obliterans (Buerger disease).
- Medial calcification with a normal intima Monckeberg sclerosis, which causes no symptoms.
A woman has a pulmonary embolus blocking the artery to her right lower lobe. What happens to ventilation and perfusion of that lobe?
Answer: Perfusion lost, ventilation preserved
An embolus blocks blood flow but not the airways, so the affected segments are ventilated but not perfused: their V/Q ratio rises towards infinity and they become alveolar dead space. On a ventilation-perfusion scan this gives mismatched defects, and several segmental mismatches make PE highly probable. Matched loss of both ventilation and perfusion means airway or parenchymal disease such as pneumonia or COPD, where hypoxic vasoconstriction secondarily cuts perfusion. Low ventilation with preserved perfusion is shunt-like, as in airway obstruction.
V/Q in PE
- PE: ventilated but not perfused
- V/Q rises: dead space
- Scan shows mismatched defects
- Matched defects: lung disease
Remember Air gets in but blood does not: think embolus.
Exam trap Matched defects do not suggest PE; it is the mismatch that counts.
Why the other options are wrong
- Both ventilation and perfusion lost Matched loss suggests airway or parenchymal disease.
- Ventilation lost, perfusion preserved Low V/Q, shunt-like; typical of airway obstruction or consolidation.
- Both preserved but redistributed The blocked artery stops flow to that lobe.
- Ventilation and perfusion both rise Perfusion cannot rise beyond a blocked artery.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Lungs, heart and vessels, Haemostasis, thrombosis and vascular disease: arterial, venous, hypertension, aneurysm
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