Clots, Veins, and Arteries
TL;DR. Blood must clot instantly when a vessel breaks and must never clot when one is intact, and the system that manages this trade-off fails in both directions. A clot forming in a deep leg vein (deep vein thrombosis) is uncomfortable and survivable; the same clot breaking loose and lodging in the lung (pulmonary embolism) is one of the leading causes of preventable death in hospital. Together they are called venous thromboembolism, they affect up to 10 million people a year, and a large share of hospital cases are preventable with measures that cost almost nothing. Separately, arteries narrowed by the same atherosclerosis that causes heart attacks starve the legs, and a swelling aorta can rupture without ever having caused a symptom.
Key takeaways
- Pulmonary embolism is a leading cause of preventable hospital death, and risk assessment plus prophylaxis on admission prevents a large share of cases.
- The three conditions that cause clots were described by Virchow in the 1850s and have not been improved on: slow flow, vessel wall injury, and blood that clots too readily.
- Long-haul flights raise clot risk roughly two to four fold, and the mechanism is immobility rather than cabin pressure. The absolute risk for a healthy person remains low.
- A newly diagnosed clot with no obvious cause can be the first sign of a cancer, and this is a genuine and under-appreciated association.
- Peripheral artery disease is a marker of disease everywhere else. People with leg claudication are at high risk of heart attack and stroke, and treating the whole picture matters more than treating the leg.
- Abdominal aortic aneurysm screening, a single ultrasound in older men, is one of the cheapest life-saving programmes in medicine.
How clotting works, and how it fails
In short: A deliberately explosive cascade held in check by an equally elaborate braking system, and disease is either arm failing.
When a vessel is injured, three things happen within seconds. Platelets stick to the exposed surface and to each other, forming a temporary plug. A cascade of clotting factors activates in sequence, each one activating more of the next, producing a burst of thrombin that converts soluble fibrinogen into insoluble fibrin strands. The fibrin mesh traps red cells and locks the plug in place.
It is deliberately positive feedback, because a small injury needs a fast, complete response. That makes it dangerous, so it is restrained by natural anticoagulants (antithrombin, protein C, protein S) and by a clot-dissolving system (fibrinolysis) that removes it when healing is done. Nearly every anticoagulant drug blocks one specific step of the cascade, and nearly every thrombolytic drug accelerates the dissolving system.
Virchow's triad, described in the 1850s, still explains why clots form where they do:
| Factor | Meaning | Examples |
|---|---|---|
| Stasis | Blood moving too slowly | Immobility, long flights, hospital admission, plaster casts, heart failure |
| Endothelial injury | Damage to the vessel lining | Surgery, trauma, catheters, inflammation, smoking |
| Hypercoagulability | Blood that clots too readily | Cancer, pregnancy, oestrogen-containing contraception and HRT, inherited thrombophilias, infection, dehydration |
Most real clots involve at least two of the three, which is why a long flight after surgery in someone on the combined pill is a genuinely different situation from any one of those alone.
Deep vein thrombosis
In short: A clot in a deep leg vein, usually presenting on one side, and the danger is what happens if it travels.
What it is. A clot in the deep veins, usually of the calf or thigh, occasionally the arm.
What it feels like: pain or aching, swelling, warmth, and redness, characteristically in one leg. Both legs swelling is more likely to be heart, kidney, or liver related. Some DVTs cause almost no symptoms.
Diagnosis starts with a clinical probability score (the Wells score), because symptoms alone are unreliable. In low-probability patients a negative D-dimer blood test, which detects breakdown products of fibrin, safely excludes it. D-dimer is sensitive and not specific: it rises in infection, inflammation, pregnancy, cancer, and after surgery, so it is only useful for ruling out, not ruling in. Confirmation is by ultrasound.
Pulmonary embolism
In short: A clot that has travelled to the lung, and it kills quietly and quickly.
What it is. A clot, usually from a leg vein, travelling through the right side of the heart and lodging in a pulmonary artery. Blood cannot reach that part of the lung, so ventilated lung receives no perfusion, oxygen falls, and, if the clot is large, the right ventricle suddenly has to pump against a blocked circuit and fails.
What it feels like: sudden breathlessness, sharp chest pain worse on breathing in, a fast heart rate, coughing (sometimes blood), light-headedness, and in large emboli, collapse. It can also present with nothing more than unexplained breathlessness or fainting, which is why it is missed.
Diagnosis: clinical probability, D-dimer, then CT pulmonary angiography.
Why it matters so much. Untreated PE has a mortality on the order of 25 to 30 percent, and it is consistently identified as one of the leading causes of preventable death in hospitalised patients. A substantial share of hospital-acquired cases are preventable with risk assessment and prophylaxis on admission, which is why many health systems mandate it.
Who is at risk
In short: Anything that immobilises, injures a vessel, or thickens the blood, and several of these are avoidable.
| Risk factor | Detail |
|---|---|
| Surgery, especially hip and knee replacement, and major cancer surgery | The highest-risk category. Prophylaxis is standard |
| Hospital admission and immobility | Even medical (non-surgical) admission raises risk substantially |
| Cancer | Raises risk several-fold, both from the cancer and from its treatment. Pancreatic, lung, brain, and haematological cancers most |
| Pregnancy and the postpartum period | Roughly a fourfold to fivefold increase, highest in the six weeks after delivery. A leading cause of maternal death in high-income countries |
| Oestrogen-containing contraception and HRT | Roughly a two to fourfold increase in relative terms, from a low baseline. Risk multiplies with smoking, obesity, and thrombophilia |
| Long-haul travel | Roughly two to fourfold for flights over about 4 hours. Mechanism is immobility |
| Obesity | Independent risk factor |
| Inherited thrombophilia | Factor V Leiden (in roughly 5 percent of people of European ancestry), prothrombin gene mutation, and rarer deficiencies of protein C, protein S, and antithrombin |
| Antiphospholipid syndrome | An acquired autoimmune clotting disorder, and an important cause in younger people and in recurrent pregnancy loss |
| Previous VTE | The strongest single predictor of another |
The cancer connection deserves emphasis. An unprovoked clot, particularly in someone over 40, can be the first manifestation of an undiagnosed cancer, and a proportion of such patients are diagnosed with cancer within the following year. Current guidance is age-appropriate screening and a careful history and examination rather than an extensive scan-everything search, which trials found did not improve outcomes.
Treatment
In short: Anticoagulate, decide for how long, and reserve clot-busting for the patients who are collapsing.
Anticoagulation does not dissolve the existing clot. It prevents it growing and prevents new ones, while the body's own fibrinolytic system breaks down what is there.
| Drug | Mechanism | Notes |
|---|---|---|
| Direct oral anticoagulants (apixaban, rivaroxaban, edoxaban, dabigatran) | Block factor Xa or thrombin directly | First-line for most patients. No routine monitoring, fewer food and drug interactions, less intracranial bleeding than warfarin |
| Low molecular weight heparin | Enhances antithrombin | Injected. Preferred in pregnancy (does not cross the placenta) and often in cancer |
| Warfarin | Blocks vitamin K-dependent factor synthesis | Requires INR monitoring and dietary consistency. Still first choice in mechanical heart valves and antiphospholipid syndrome |
How long to treat is the central decision:
| Situation | Typical duration |
|---|---|
| Provoked by a temporary factor (surgery, cast, a specific immobilisation) | 3 months |
| Unprovoked | At least 3 to 6 months, then an individual decision about extended treatment, because recurrence risk is high |
| Cancer-associated | While cancer is active |
| Recurrent, or high-risk thrombophilia | Often indefinite |
Thrombolysis ("clot-busting") is reserved for massive PE with haemodynamic collapse, because it carries a real risk of major bleeding including intracranial haemorrhage. Catheter-directed techniques are used in selected intermediate-risk patients.
An inferior vena cava filter, a device catching clots travelling from the legs, is used when anticoagulation is impossible, and should be retrieved once it is not needed, because they cause complications when left indefinitely.
Prevention
In short: Nearly free, well proven, and still inconsistently applied.
In hospital: every patient should have a documented VTE risk assessment on admission, with mechanical prophylaxis (graduated compression stockings, intermittent pneumatic compression) and pharmacological prophylaxis (usually low-dose low molecular weight heparin) unless contraindicated. Early mobilisation matters. National programmes mandating this have measurably reduced hospital-associated VTE.
On long flights: move, walk the aisle when you can, do calf exercises seated, stay hydrated, and avoid excess alcohol. Compression stockings reduce risk and are worth it for people with additional risk factors. Aspirin is not effective prophylaxis for this. Anticoagulant prophylaxis is considered only for high-risk travellers.
After surgery: follow the prophylaxis plan for its full duration, which after hip and knee replacement often extends for weeks after discharge, and is the period during which people stop because they feel well.
Varicose veins and chronic venous disease
In short: Failed one-way valves letting blood pool, and the serious end of the spectrum is a leg ulcer.
Leg veins carry blood upward against gravity, assisted by one-way valves and by the calf muscle pump: contracting calf muscles squeeze the deep veins and push blood up. When valves fail, blood falls back and pools.
| Stage | Features |
|---|---|
| Varicose veins | Dilated, tortuous surface veins. Often cosmetic; can cause aching, heaviness, and itching |
| Chronic venous insufficiency | Persistent swelling, brown pigmentation around the ankle (from leaked red cells), and hardened skin |
| Venous leg ulcer | Breakdown of skin, classically around the inner ankle. Chronic, painful, and slow to heal |
Venous ulcers are the commonest cause of chronic leg ulceration, and the treatment is compression: firm graduated bandaging or stockings, which supports the failing veins and heals a large proportion of ulcers. Compression must not be applied without first excluding arterial disease (by measuring the ankle-brachial index), because compressing a leg with poor arterial supply causes harm.
Varicose veins themselves are treated by endovenous laser or radiofrequency ablation, foam sclerotherapy, or surgery, mostly when symptomatic or complicated rather than for appearance.
Peripheral artery disease
In short: The same disease as coronary artery disease, in the legs, and a strong marker of risk everywhere else.
What it is. Atherosclerosis narrowing the arteries supplying the legs (Chapter 21).
What it feels like. Intermittent claudication: cramping pain in the calf, thigh, or buttock brought on by walking a predictable distance and relieved by standing still within a few minutes. The distinction from spinal claudication matters: spinal stenosis pain is relieved by bending forward or sitting rather than by simply stopping.
Severe disease produces pain at rest, typically in the foot at night and relieved by hanging the leg out of bed, non-healing ulcers, and gangrene. This is chronic limb-threatening ischaemia and is an emergency for the limb.
Diagnosis: the ankle-brachial index, comparing blood pressure at the ankle with the arm. A ratio below 0.9 indicates disease. It is quick and cheap.
The crucial point. People with peripheral artery disease have a substantially increased risk of heart attack and stroke, and more of them die of cardiovascular events than lose limbs. So treatment is:
- Risk factor treatment first: stopping smoking (the single most important intervention), statin, antiplatelet, blood pressure control, diabetes control.
- Supervised exercise therapy: walking to near-maximal claudication pain, resting, repeating, three times a week. It improves walking distance as much as or more than stenting, and it is dramatically underused.
- Revascularisation (angioplasty, stenting, or bypass) for lifestyle-limiting symptoms despite the above, or for limb-threatening ischaemia.
Acute limb ischaemia, a sudden arterial blockage, presents with the six Ps: pain, pallor, pulselessness, paraesthesia, paralysis, and perishing cold. It is a surgical emergency with a window of hours.
Aneurysms and dissection
In short: A silent swelling that kills when it bursts, and one of the cheapest screening programmes in existence.
An aneurysm is a permanent localised dilatation of an artery, most consequentially the abdominal aorta. It grows silently. If it ruptures, mortality is very high, with a large proportion of patients dying before reaching hospital.
Abdominal aortic aneurysm screening, a single ultrasound offered to men around age 65, reduces aneurysm-related mortality substantially and is one of the most cost-effective screening programmes running. Risk factors are age, male sex, smoking (by far the strongest modifiable one), hypertension, and family history. Small aneurysms are monitored; larger ones (typically above 5.5 cm) are repaired electively, which is far safer than emergency repair.
Aortic dissection is different and acute: the inner layer of the aorta tears and blood forces its way between the layers, splitting the wall. It causes sudden, severe, tearing chest or back pain, often described as the worst pain of the person's life and often migrating as the tear extends. It is a time-critical emergency, hypertension is the leading risk factor, and it is associated with connective tissue disorders such as Marfan syndrome (Chapter 49).
Brain aneurysms rupture into the space around the brain, causing subarachnoid haemorrhage (Chapter 22).
Raynaud's phenomenon
In short: Small arteries in fingers and toes over-constricting, usually harmless and occasionally a clue to something else.
Cold or stress triggers exaggerated constriction of the small arteries in the fingers and toes, which turn white, then blue, then red as flow returns, often painfully.
Primary Raynaud's is common, benign, usually starts young, and needs only warmth and avoidance of triggers, with calcium channel blockers if severe.
Secondary Raynaud's is a marker of underlying disease, particularly systemic sclerosis, lupus, or other connective tissue disease (Chapter 47). Features suggesting it: onset after 30, asymmetry, ulceration of the fingertips, and abnormal nailfold capillaries. Those warrant investigation.
What the person can do
In short: Move, know the emergency signs, and take prophylaxis seriously when it is offered.
- Know the emergency symptoms. Sudden breathlessness with sharp chest pain, one-sided leg swelling with pain, sudden tearing chest or back pain, and a cold pulseless painful limb all mean emergency care now.
- On admission to hospital or before surgery, ask whether you need clot prevention, and complete the full course after discharge if it is prescribed.
- Move on long journeys, and use compression stockings if you have any additional risk factor.
- Stop smoking. It is the dominant modifiable risk factor for peripheral artery disease and for aortic aneurysm, and it is a risk factor for clots.
- If you have claudication, walk. Supervised exercise therapy works, and stopping walking because it hurts makes it worse.
- If you are offered aneurysm screening, take it. One scan, once, and it prevents a death that otherwise gives no warning.
- If you have had an unprovoked clot, discuss how long to continue anticoagulation, and make sure age-appropriate cancer screening is up to date.
- If you take an anticoagulant, know your bleeding risks, tell every clinician and dentist, and do not stop it before a procedure without specific advice.
Sources and notes
VTE incidence and hospital-associated proportion: ISTH and national epidemiological analyses; estimates of up to 10 million cases a year worldwide. Preventable hospital death attribution: UK House of Commons Health Committee report and subsequent national VTE prevention programmes. Virchow's triad: Virchow, 1856. Untreated PE mortality: historical natural history studies (Barritt and Jordan, The Lancet, 1960). Wells scores and D-dimer strategies: validated in multiple management studies. Travel-related VTE risk: WHO WRIGHT project. Factor V Leiden prevalence in European ancestry populations: population genetic surveys. Occult cancer screening after unprovoked VTE: SOME trial, NEJM, 2015, which found extensive screening did not improve detection or outcomes. DOAC versus warfarin: EINSTEIN, AMPLIFY, RE-COVER, and Hokusai trials. Supervised exercise versus revascularisation in claudication: CLEVER trial and Cochrane reviews. AAA screening mortality benefit: MASS trial, The Lancet, and long-term follow-up. Compression for venous ulceration: Cochrane reviews.
Open questions. How long to anticoagulate after a first unprovoked VTE remains a genuine judgement call, balancing recurrence against bleeding. Whether inherited thrombophilia testing changes management in most patients is debated, and many guidelines now discourage routine testing.
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