Deep-vein thrombosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Deep-vein thrombosis is fibrin-rich clot within the deep venous system, most often in the leg. Proximal DVT involves popliteal, femoral or iliac veins and carries greater embolic risk than isolated calf thrombosis. Symptoms are non-specific: unilateral swelling, tenderness, pitting oedema and dilated superficial veins occur in infection, injury and chronic venous disease. NICE therefore combines a two-level Wells probability with D-dimer and compression ultrasonography rather than treating clinical impression or D-dimer as diagnostic.

In a likely Wells pathway, ultrasound comes first. If imaging is negative, a D-dimer identifies who needs repeat scanning in 6–8 days. In an unlikely pathway, D-dimer comes first and a negative result ends the DVT investigation in most adults. Age-adjusted thresholds may improve specificity in people over 50 when the local assay and pathway support them. When a time-critical test is unavailable, interim therapeutic anticoagulation prevents propagation; obtain FBC, renal and liver function, PT and APTT first where this does not delay the dose.

Treatment prevents extension, embolisation and recurrence while endogenous fibrinolysis and recanalisation occur. Apixaban and rivaroxaban include their own higher-dose oral initiation phases and do not require preceding heparin. Dabigatran and edoxaban require at least 5 days of parenteral anticoagulation. Warfarin requires heparin overlap because its initial protein C reduction can be prothrombotic. Severe renal impairment, active cancer, APS, pregnancy, extreme weight, interactions and imminent procedures change agent choice.

Every clot needs an aetiological and duration review, not an indiscriminate cancer scan or thrombophilia panel. History and examination identify surgery, immobility, oestrogen, pregnancy, inflammatory disease and cancer symptoms. Continue age-appropriate cancer screening and investigate only clinical clues beyond routine assessment. At three months, a major transiently provoked event usually supports stopping, while unprovoked, recurrent, cancer-associated or persistent-risk thrombosis often supports extended therapy if bleeding risk is acceptable.

Key points

DVT commonly causes unilateral swelling, pain, pitting oedema, warmth and superficial collateral veins, but examination cannot confirm or exclude it; calculate the two-level DVT Wells score.
DVT likely means Wells score 2 or more: arrange proximal leg-vein ultrasound within 4 hours where possible and obtain D-dimer if ultrasound is negative.
DVT unlikely means Wells score 1 or less: obtain D-dimer first; a negative appropriately interpreted test excludes DVT, while a positive result leads to ultrasound.
If the required ultrasound or D-dimer is delayed beyond the NICE pathway time, give interim therapeutic anticoagulation unless contraindicated after drawing baseline bloods; results need not return first.
When initial proximal ultrasound is negative but D-dimer is positive, repeat proximal ultrasound 6–8 days later because early or distal clot may propagate into the scanned segment.
For confirmed proximal DVT, offer apixaban or rivaroxaban first-line when suitable: apixaban 10 mg twice daily for 7 days then 5 mg twice daily; rivaroxaban 15 mg twice daily for 21 days then 20 mg daily with food.
Treat for at least 3 months, then decide stop or extend from transient provocation, active cancer, recurrence, APS, bleeding risk and preference; do not use thrombophilia testing as a substitute for this review.
Do not routinely offer graduated compression stockings solely to prevent post-thrombotic syndrome, but they may be used for persistent leg symptoms after assessing arterial supply and fit.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Transient provoking factors

Major surgery, trauma, lower-limb immobilisation, hospital admission, pregnancy, puerperium and oestrogen exposure temporarily combine stasis, endothelial injury and hypercoagulability.

Persistent acquired risk

Active cancer, inflammatory disease, obesity, paralysis, nephrotic syndrome, APS, myeloproliferative neoplasm and indwelling venous devices maintain risk beyond one episode.

Inherited and anatomical risk

Factor V Leiden and rarer natural-anticoagulant deficiencies modify risk, while May-Thurner compression and thoracic-outlet anatomy create site-specific venous stasis.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Stasis initiates venous clot
Reduced calf-muscle pumping and obstructed flow allow activated factors to accumulate around valve pockets, where low oxygen and inflammation promote thrombosis.
2
Endothelial and coagulation activation
Surgery, trauma, cancer and inflammation increase tissue factor, platelet-endothelial signalling and thrombin generation while natural anticoagulant pathways become less effective.
3
Propagation and embolisation
Fibrin-rich thrombus can extend from calf to popliteal, femoral and iliac veins; detached fragments travel through the right heart to pulmonary arteries.
4
Venous valve injury
Residual obstruction and inflammatory valve damage cause reflux, ambulatory venous hypertension, oedema, skin change and post-thrombotic syndrome after the acute clot.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical unilateral pattern

Calf or whole-leg swelling, deep tenderness, warmth, pitting oedema and new superficial collaterals raise probability but remain non-specific.

Proximal or iliac disease

Whole-leg swelling, buttock or groin pain and prominent abdominal collaterals suggest proximal obstruction that a limited calf examination may miss.

Upper-limb thrombosis

Arm and neck swelling, venous distension and catheter or thoracic-outlet context require an upper-limb duplex and central-vein assessment.

Provoking context

Recent operation, immobilisation, hospitalisation, oestrogen, pregnancy, cancer or previous VTE materially raises pre-test probability and informs duration.

Threatened limbRed flag

Extreme pain, cyanosis, massive swelling, sensory loss or reduced pulses indicates phlegmasia and demands immediate vascular escalation.

Red flags requiring action

Cyanosis, severe tense swelling, blistering, neurological deficit or reduced arterial signals suggests phlegmasia cerulea dolens and threatened venous gangrene.
New dyspnoea, pleuritic pain, haemoptysis, syncope, hypotension or unexplained tachycardia may indicate pulmonary embolism and changes urgency and imaging.
Extensive iliofemoral thrombosis in a young person, bilateral disease, recurrent clot or an unusual site should prompt assessment for anatomical obstruction, cancer, APS or myeloproliferative disease.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line: two-level DVT Wells scoreFirst stepFirst line
Why
Choose ultrasound-first or D-dimer-first testing and avoid unstructured probability estimates.
Interpretation and limitations
A score of 2 or more is DVT likely and 1 or less is DVT unlikely. An alternative diagnosis at least as likely subtracts points and requires genuine clinical judgment.
02
First-line in unlikely DVT: D-dimerFirst line
Why
Exclude thrombosis safely when clinical probability is low.
Interpretation and limitations
A negative validated assay rules out DVT in the unlikely pathway; a positive result is non-specific and requires ultrasound. Use age adjustment only through a validated local route.
03
Confirmatory proximal compression ultrasoundConfirmatory
Why
Demonstrate failure of venous compressibility or visualised thrombus in the proximal deep system.
Interpretation and limitations
A positive scan confirms DVT. If negative after a likely score, check D-dimer; positive D-dimer requires repeat proximal ultrasound 6–8 days later.
04
Baseline anticoagulation bloods
Why
Select and dose treatment safely without delaying necessary interim anticoagulation.
Interpretation and limitations
Send FBC, renal and liver function, PT and APTT and pregnancy testing when relevant. Results can reveal anaemia, thrombocytopenia or organ impairment that changes drug choice.
05
Selective cause testing
Why
Find persistent disease only when phenotype or a management decision justifies investigation.
Interpretation and limitations
Use focused cancer assessment, APS tests and selected hereditary testing after the acute phase. Do not offer broad cancer imaging or thrombophilia panels routinely after provoked DVT.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cellulitis and soft-tissue infection

Diffuse erythema, warmth, fever and a portal of entry favour infection, but cellulitis and DVT can coexist and neither is excluded by D-dimer alone.

Ruptured Baker cyst

Acute calf pain and swelling after knee symptoms can track fluid down fascial planes; ultrasound distinguishes cystic fluid and venous compressibility.

Superficial vein thrombosis

A tender palpable cord follows a superficial vein, but proximity to the saphenofemoral junction or extensive disease requires duplex assessment for deep extension.

Lymphatic or cardiac oedema

Chronic non-pitting change, bilateral swelling, heart failure, hypoalbuminaemia and venous insufficiency have different tempo, though acute asymmetry still needs DVT assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DVT likelyUltrasound before D-dimerFirst stepThe two-level DVT Wells score is 2 or more.

1Arrange proximal leg-vein ultrasound within 4 hours where possible and give interim therapeutic anticoagulation if imaging will be delayed.
2Treat a positive scan as confirmed DVT; if negative, obtain D-dimer and stop interim anticoagulation when the pathway excludes thrombosis.
3If ultrasound is negative and D-dimer positive, repeat proximal ultrasound 6–8 days later and maintain or stop interim therapy according to NICE timing and risk.

02DVT unlikelyD-dimer before imagingThe two-level DVT Wells score is 1 or less.

1Obtain D-dimer within 4 hours where possible, using an age-adjusted threshold only when validated for the assay and pathway.
2If negative, stop interim anticoagulation and consider another diagnosis; if positive, arrange proximal ultrasound within the recommended timeframe.
3AlternativeTreat a positive scan and, after a negative scan in this branch, stop interim anticoagulation and pursue the alternative diagnosis.

03Confirmed DVTChoose agent and minimum durationUltrasound confirms proximal DVT or another deep venous site is objectively demonstrated.

1Assess bleeding, renal and liver function, pregnancy, cancer, APS, weight, interactions, adherence and planned procedures before choosing the regimen.
2First lineUse apixaban or rivaroxaban first-line when suitable, prescribe the loading-to-maintenance transition explicitly and treat for at least 3 months.
3Provide bleeding and recurrence advice and schedule the three-month stop-versus-extend review before the initial prescription ends.

04Iliofemoral or phlegmasiaAssess urgent thrombus removalSymptoms began within approximately 14 days and extensive proximal clot threatens limb or causes severe functional compromise.

1Start therapeutic anticoagulation and obtain urgent vascular imaging and specialist assessment of arterial inflow, bleeding and symptom duration.
2For phlegmasia or threatened limb, consider immediate catheter-directed thrombolysis, pharmacomechanical therapy or surgical thrombectomy in an experienced centre.
3Continue anticoagulation after intervention and address anatomical compression, malignancy and post-thrombotic symptom prevention.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

NICE first-line oral treatment for confirmed DVT when suitable, without a parenteral heparin lead-in.

Apixaban

Give 10 mg orally twice daily for the first 7 days, then 5 mg twice daily; treat for at least 3 months and, if extended prevention is chosen after 6 months, consider 2.5 mg twice daily according to recurrence and bleeding risk.

Check active bleeding, renal and liver function, pregnancy, APS and CYP3A4 or P-gp interactions. The atrial-fibrillation dose-reduction rule does not apply to initial VTE treatment, and missed loading doses under-treat acute clot.

NICE first-line single-drug oral regimen for acute and continuing DVT treatment in suitable adults.

Rivaroxaban

Give 15 mg orally twice daily with food for 21 days, then 20 mg once daily with food; after at least 6 months, 10 mg once daily may be used for selected extended prevention, with 20 mg retained when recurrence risk is high.

Write the transition date and food instruction. Review renal and hepatic impairment, pregnancy, APS, active cancer bleeding sites and strong CYP3A4 or P-gp interactions; do not continue 15 mg twice daily beyond 21 days.

Provides interim and definitive parenteral anticoagulation in pregnancy, selected cancer, oral-treatment contraindication or when rapid interruption is needed.

Enoxaparin

Give 1.5 mg/kg subcutaneously once daily or 1 mg/kg every 12 hours for acute DVT according to the product and specialist pathway; use 1 mg/kg once daily in severe renal impairment with anti-Xa advice where indicated.

Use actual body weight, review platelets and HIT history, renal function, neuraxial procedures and active bleeding. Pregnancy and extremes of weight need a documented specialist monitoring and delivery plan.

Treats DVT when DOAC therapy is unsuitable, including selected APS, severe renal impairment and interaction or access circumstances.

Warfarin

Begin alongside therapeutic LMWH or UFH, continue parenteral treatment for at least 5 days and until INR is at least 2.0 on the locally required consecutive measurements, then maintain INR 2.0–3.0.

It is teratogenic and highly interactive. Monitor INR, diet, alcohol and adherence; initial protein C depletion makes adequate heparin overlap essential, and major bleeding requires PCC plus intravenous vitamin K.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pulmonary embolism

Embolisation can cause pleuritic symptoms, infarction, right-ventricular failure, shock or cardiac arrest and is the principal acute life-threatening complication.

Post-thrombotic syndrome

Chronic pain, heaviness, swelling, hyperpigmentation, lipodermatosclerosis and ulceration follow venous hypertension after incomplete recanalisation or valve destruction.

Recurrent thrombosis

Risk is greatest after unprovoked or persistent-risk events, cancer, APS, previous recurrence and premature anticoagulant discontinuation.

Anticoagulant bleeding

Gastrointestinal, intracranial, menstrual, procedural and occult bleeding depends on drug, renal function, interactions, age and underlying lesion and can alter treatment duration.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review within the initial treatment phase to confirm correct loading dose, transition date, adherence, renal and liver function, bleeding and symptom improvement.
Give immediate-return advice for dyspnoea, chest pain, syncope, haemoptysis, major bleeding, worsening swelling or neurovascular change rather than relying on a routine appointment.
At three months, document whether the event was provoked, cancer-associated, recurrent or unprovoked and make a shared stop, continue full treatment or extended prevention decision.
For persistent leg symptoms, assess post-thrombotic syndrome, recurrent clot, venous obstruction and alternative musculoskeletal or lymphatic causes; do not use D-dimer as recurrence surveillance.
During extended anticoagulation, review at least annually and after major illness for bleeding, recurrence, renal and liver change, interactions, weight, pregnancy and preference.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

D-dimer excludes, not confirms

Its value comes from a negative result in a low-probability pathway; infection, cancer, age and pregnancy commonly make it positive without DVT.

Negative ultrasound may need repetition

A positive D-dimer after a likely score identifies patients whose initially distal or subtle clot may enter the proximal segment by day six to eight.

Loading phases differ

Apixaban needs seven high-dose days and rivaroxaban twenty-one, while dabigatran and edoxaban require preceding heparin.

Provocation directs duration

A transient surgical trigger and an unprovoked proximal clot have different recurrence risks even when the ultrasound appearance is identical.

Cirrhosis does not exclude DVT

A prolonged INR in liver disease does not reflect balanced anticoagulation and should not remove a patient from probability-led investigation.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing DVT from a positive D-dimer alone.
02
Skipping the Wells score and using an improvised sequence.
03
Omitting interim anticoagulation when imaging is substantially delayed.
04
Forgetting repeat ultrasound after a negative scan and positive D-dimer in the likely pathway.
05
Applying atrial-fibrillation apixaban reductions to acute DVT.
06
Ordering broad thrombophilia and cancer panels after every provoked event.