18.10 — Clots and Embolism

Rudolf Virchow described the three conditions that produce a clot in 1856, and the triad has not needed revising.

Stasis — blood not moving. Endothelial injury — a damaged vessel wall. Hypercoagulability — blood that clots too readily.

Every risk factor for venous thrombosis maps onto one of the three, which makes it one of the more satisfying frameworks in medicine — and a genuinely useful one, because it tells you what to prevent.

Why clots form where they do

Venous clots form in slow-moving blood — mostly in the deep veins of the legs, where the calf muscle pump is what keeps blood moving (Chapter 6.6).

Which is why immobility is the dominant risk factor: no pump, stagnant blood, clot.

Arterial clots are different — they form on ruptured plaques in fast-moving blood, and they are platelet-rich rather than fibrin-rich (Chapter 18.1).

Which is why they are treated differently. Antiplatelet drugs for arterial clots; anticoagulants for venous. Confusing the two is a genuine and consequential error.

Deep vein thrombosis

Symptoms: swelling of one leg, pain or tenderness in the calf, warmth, and redness.

And one-sidedness is the useful feature. Both legs swelling is usually heart failure, liver disease or venous insufficiency, not a clot.

But around half of DVTs cause no symptoms at all, which is why the first presentation is sometimes the pulmonary embolism.

Risk factors, grouped by Virchow:

Stasis — immobility, long-haul travel, hospital admission, surgery, plaster casts, paralysis.

Endothelial injury — surgery, trauma, previous DVT, central lines.

Hypercoagulability — cancer, pregnancy and the postpartum period, oestrogen-containing contraception and HRT, obesity, smoking, dehydration, inflammatory disease, and inherited thrombophilias.

And cancer deserves specific mention. An unprovoked clot can be the first sign of an undiagnosed cancer, and around 5 to 10 percent of people with an unprovoked venous thrombosis have a cancer diagnosed within a year. Which is why a careful history, examination and age-appropriate screening follow — though extensive scanning for occult cancer has not been shown to improve outcomes.

Inherited thrombophilias — factor V Leiden being the commonest, present in around 5 percent of people of European descent.

And testing for them is far less useful than people expect. The result rarely changes management — the decision on how long to anticoagulate is driven mainly by whether the clot was provoked and by bleeding risk. Routine thrombophilia testing after a first provoked clot is explicitly not recommended.

Pulmonary embolism

A clot travelling to the lungs, and it is the dangerous consequence.

Symptoms: sudden breathlessness, sharp chest pain worse on breathing (Chapter 8.2), coughing blood, fast heart rate, and light-headedness or collapse.

And it is one of the great mimics. It presents as pneumonia, as a heart attack, as anxiety, and as unexplained collapse — which is why it is among the most frequently missed serious diagnoses.

Massive PE — with low blood pressure — carries high mortality and needs thrombolysis or clot removal.

And a physiological point that catches people out (Chapter 8.4): a person with a pulmonary embolism can have a normal oxygen saturation. The affected lung region is ventilated but not perfused — dead space — and the rest of the lung compensates. A normal saturation does not exclude it.

Diagnosis

Clinical probability first, using a structured score — Wells or similar — because it determines what the tests mean (Chapter 16.4).

D-dimer — a fibrin breakdown product.

And its use is frequently got wrong. A normal D-dimer in someone at low or moderate probability effectively excludes the diagnosis, and that is its entire value.

A raised D-dimer means very little, because it rises in infection, inflammation, pregnancy, cancer and after surgery.

And it should not be ordered in someone at high probability, because a negative result will not change the plan and a positive one adds nothing — the imaging is needed either way.

Imaging: ultrasound of the leg for DVT; CT pulmonary angiography for PE, or a ventilation–perfusion scan where contrast is contraindicated, particularly in pregnancy (Chapter 16.6).

Treatment

Anticoagulation.

Direct oral anticoagulants — apixaban, rivaroxaban, edoxaban, dabigatran — are now first-line for most. No monitoring, fixed dosing, fewer interactions, and less bleeding than warfarin.

Warfarin remains necessary in antiphospholipid syndrome, mechanical valves and severe kidney impairment.

Low molecular weight heparin — used in pregnancy, because it does not cross the placenta, and in cancer-associated thrombosis, though the oral agents are increasingly used there too.

Duration:

Provoked by a transient factor — surgery, a cast, a flight — 3 months.

Unprovoked — at least 3 to 6 months, and often indefinite, because the recurrence risk after stopping is around 10 percent in the first year and 30 percent at five years.

And the decision balances that against bleeding risk, which is why it is individualised rather than protocolised.

Thrombolysis — for massive PE with haemodynamic compromise, and for extensive limb-threatening DVT.

Inferior vena cava filters — for people who cannot be anticoagulated. They prevent PE and do not treat the clot, they increase DVT recurrence, and they should be removed when no longer needed — a substantial number are not, which is a recognised problem.

The long-term consequences

Post-thrombotic syndrome — affecting 20 to 50 percent after a DVT.

Chronic leg swelling, aching, skin changes and, in severe cases, ulceration (Chapter 14.4) — caused by damaged valves and persistent venous hypertension.

Compression stockings help symptoms, and the evidence that they prevent the syndrome is weaker than was once believed.

Chronic thromboembolic pulmonary hypertension — in a small percentage after PE, and it is potentially curable by surgery, which makes it worth looking for in anyone with persistent breathlessness months after a PE.

Prevention

And this is where most of the benefit lies, because a substantial proportion of venous thromboembolism is hospital-associated and preventable.

In hospital: risk assessment on admission, early mobilisation, hydration, compression stockings or intermittent pneumatic compression, and prophylactic anticoagulation where the risk warrants it.

Venous thromboembolism risk assessment is now a mandated quality measure in several health systems, precisely because it works and was inconsistently done.

After surgery — particularly hip and knee replacement, which carry high risk — extended prophylaxis for several weeks.

In pregnancy and postpartum — the highest-risk period is the six weeks after delivery (Chapter 15.7), and it remains a leading cause of maternal death.

Long-haul travel — the risk is real and small, roughly doubling for flights over four hours, and rising with duration.

Practical measures: walk every couple of hours; do calf exercises in the seat — which activates the muscle pump directly; stay hydrated; and avoid excess alcohol and sedatives.

Compression stockings reduce risk for those at higher risk. Aspirin is not adequate for this purpose. And routine anticoagulation for flights is not recommended for people at ordinary risk.

Bleeding risk

Because anticoagulation is a trade, and it should be presented as one.

Major bleeding occurs in around 2 to 3 percent per year on anticoagulation, and intracranial bleeding in around 0.2 to 0.5 percent.

Reversal agents exist — vitamin K and clotting factor concentrates for warfarin; specific antidotes for dabigatran and for the factor Xa inhibitors — which has substantially improved the safety of the newer drugs.

And practical advice for anyone anticoagulated: carry an alert card; tell any dentist or surgeon; be careful with NSAIDs, which add to bleeding risk; and seek help for any head injury, however minor it seems, because a bleed can develop over hours.

What has improved

Recognition and prevention in hospital, which has reduced hospital-associated thrombosis substantially where risk assessment is systematic.

Direct oral anticoagulants, which removed the monitoring burden that made warfarin so difficult.

Reversal agents, which removed the main objection to them.

And better diagnostic pathways, which use clinical probability properly rather than testing everyone.

Venous thromboembolism remains common and remains one of the most preventable causes of hospital death. Most of the remaining harm comes from not thinking of it.

What Part 19 does next

The conditions in this Part share a pattern: decades of silent development, strong modifiable risk factors, and treatments that work best when started early.

Part 19 covers a disease that shares the first of those and differs in the rest — cancer, where the last twenty years have produced changes that would have seemed implausible when this century began.