Venous thromboembolism
Description
- One disease, two presentations: DVT and PE
- Classification by provoking factor determines duration of anticoagulation - this is the whole point of the classification
| Category | Definition | Recurrence at 5 yrs off anticoagulation |
|---|---|---|
| Provoked - major transient | Surgery >30 min under GA, caesarean, hospitalisation >=3 days with immobility, trauma with fracture, in the preceding 3 months | ~3% |
| Provoked - minor transient | Long-haul travel, minor surgery, oestrogen therapy, pregnancy/puerperium, leg injury with reduced mobility >3 days | ~15% |
| Provoked - persistent | Active cancer, IBD, antiphospholipid syndrome, chronic immobility | High, ongoing |
| Unprovoked | No identifiable factor | ~30% |
- Other patterns: superficial vein thrombosis (extends to DVT in ~10% - treat if >5 cm or within 3 cm of the saphenofemoral junction), distal (calf) DVT, upper limb DVT (usually catheter-related), splanchnic and cerebral venous thrombosis
Epidemiology
- Incidence ~1-2/1,000/year; rises steeply with age to ~1/100/year over 80
- ~17,000 Australian hospitalisations and ~5,000 deaths per year
- 60% of VTE is hospital-associated - the largest preventable cause of hospital death
- M=F overall; F>M in reproductive years (oestrogen, pregnancy)
- Recurrence: highest in the first 6-12 months after cessation
Aetiopathogenesis
Virchow triad
- Stasis - immobility, travel, surgery, plaster, paralysis, obesity, pregnancy
- Endothelial injury - surgery, trauma, catheters, previous DVT
- Hypercoagulability - inherited or acquired
Inherited thrombophilia
| Prevalence | Relative risk | |
|---|---|---|
| Factor V Leiden heterozygous | 3-7% Europeans | 3-5x |
| Factor V Leiden homozygous | 0.1% | 10-80x |
| Prothrombin G20210A | 1-3% | 2-3x |
| Protein C / S deficiency | 0.2-0.5% | 10x |
| Antithrombin deficiency | 0.02% | 20-50x - the most thrombogenic |
- Inherited thrombophilia raises the risk of a first event but has little effect on recurrence risk - which is why testing rarely changes management
Acquired
- Malignancy (highest with pancreas, stomach, brain, lung, ovary, myeloproliferative)
- Antiphospholipid syndrome - the one thrombophilia that changes management
- Oestrogen (COCP ~3x, HRT ~2x), pregnancy and 6 weeks postpartum (~5x, highest in the puerperium)
- Nephrotic syndrome, PNH, IBD, HIT, obesity, smoking, long-haul flight >4 h
Diagnosis
Never diagnose or exclude VTE on clinical impression alone. Use a validated pathway.
Step 1 - pre-test probability
- Wells score for DVT and for PE; alternatively Geneva score
- PERC rule - in a low-risk patient, all 8 criteria negative excludes PE without D-dimer
Step 2 - D-dimer
- Only useful to exclude, and only in low/intermediate probability
- Age-adjusted cut-off over 50: age x 10 microg/L (FEU) - improves specificity without losing sensitivity
- YEARS algorithm in pregnancy and generally - reduces imaging
- Raised in pregnancy, sepsis, malignancy, post-op, age - a positive result means nothing on its own
Step 3 - imaging
- DVT: compression ultrasound with Doppler. Negative proximal scan in a high-probability patient -> repeat at 7 days, or whole-leg scan
- PE: CTPA first-line
- V/Q or V/Q SPECT if renal impairment, contrast allergy, pregnancy (lower fetal dose from V/Q, lower maternal breast dose than CTPA - discuss with the patient)
- Bedside echo for RV strain if too unstable for CT
Risk stratification in PE - drives disposition
| Features | Management setting | |
|---|---|---|
| High-risk (massive) | Hypotension SBP <90 or shock | Thrombolysis, ICU |
| Intermediate-high | RV dysfunction on echo/CT AND raised troponin | Monitored bed, rescue thrombolysis if deteriorating |
| Intermediate-low | One of the two | Ward |
| Low-risk | PESI class I-II or sPESI 0 | Consider outpatient management |
Investigate for a cause - selectively
- Age-appropriate cancer screening + history, examination, FBE, LFT, UEC, CXR, urinalysis
- Extensive occult malignancy screening (CT abdomen/pelvis, tumour markers) does NOT improve outcome - SOME trial
- Thrombophilia testing: almost never indicated
- Does not alter duration of therapy in most cases; results are unreliable during acute thrombosis and on anticoagulation
- Test only if it will change management: suspected antiphospholipid syndrome, or antithrombin deficiency in a strong family history
- Antiphospholipid screen (lupus anticoagulant, anticardiolipin, anti-beta2GPI) in unprovoked VTE in the young, recurrent VTE, or with autoimmune features - a positive result mandates warfarin, not a DOAC
Management
A. Anticoagulation - initiation
- DOACs are recommended over vitamin K antagonists unless contraindicated - lower recurrence and less major bleeding
| Drug | Regimen |
|---|---|
| Apixaban | 10 mg bd for 7 days -> 5 mg bd (no lead-in heparin) |
| Rivaroxaban | 15 mg bd for 21 days -> 20 mg daily (no lead-in; take with food) |
| Dabigatran | 5 days LMWH first, then 150 mg bd |
| Warfarin | LMWH bridge until INR 2-3 for 2 days |
| LMWH (enoxaparin 1 mg/kg bd) | Preferred in pregnancy, severe renal impairment (use UFH if CrCl <30), and often in cancer |
- DOACs are contraindicated in: antiphospholipid syndrome (especially triple-positive - higher arterial event rate than warfarin), pregnancy and breastfeeding, mechanical valves, CrCl <15-30, severe liver disease
- Cancer-associated VTE: apixaban or rivaroxaban, or LMWH
- Avoid DOACs with luminal GI or genitourinary tumours - higher mucosal bleeding
B. Duration - by provoking factor
| Category | Duration |
|---|---|
| Provoked by a transient risk factor (surgery, immobility, long-haul travel) | Minimum 3 months, then stop |
| Unprovoked, first event | 3-6 months minimum, then consider extended (indefinite) therapy balancing bleeding risk |
| Persistent risk factor (active cancer, APS) | Indefinite, while the factor persists |
| Recurrent unprovoked VTE | Indefinite |
| Isolated distal (calf) DVT, low risk | 6 weeks, or serial ultrasound surveillance without anticoagulation |
- Extended-phase dosing: reduced-dose DOAC (apixaban 2.5 mg bd, rivaroxaban 10 mg daily) is as effective as full dose with significantly less bleeding
- Aspirin is a weak alternative (~30% risk reduction) only if anticoagulation is refused or unsafe
- Decision aids: HERDOO2 (women), Vienna prediction model; residual vein obstruction and a raised D-dimer one month after stopping predict recurrence
- Bleeding risk assessment at every review - it changes over time; extended therapy is a decision to be revisited annually, not a one-off
C. High-risk PE
- Systemic thrombolysis (alteplase 100 mg over 2 h, or 0.6 mg/kg over 15 min) for haemodynamic instability
- Catheter-directed thrombolysis or thrombectomy if absolute contraindication to lysis or failed lysis
- IVC filter only if anticoagulation is absolutely contraindicated - retrieve as soon as possible
D. Supportive
- Early mobilisation, graduated compression stockings for symptoms (they do not prevent post-thrombotic syndrome)
- Analgesia; avoid NSAIDs on anticoagulation
- Oestrogen cessation and alternative contraception advice
- Written anticoagulation information, MedicAlert, adherence emphasis
E. Prevention
- VTE risk assessment on every hospital admission - the single highest-yield intervention
- Enoxaparin 40 mg daily, or mechanical prophylaxis if bleeding risk
- Extended prophylaxis 28-35 days after hip/knee arthroplasty and major abdominopelvic cancer surgery
Associations
- Malignancy (~20% of VTE; ~5-10% of unprovoked VTE has occult cancer at 12 months)
- Antiphospholipid syndrome, SLE
- Pregnancy and puerperium; COCP and HRT
- Myeloproliferative neoplasms (JAK2 - especially in splanchnic vein thrombosis), PNH
- Nephrotic syndrome, IBD, Behcet disease
- Obesity, smoking, long-haul travel
- Heparin-induced thrombocytopenia
- COVID-19 and other acute infection
Natural history & complications
- Recurrence highest in the first 6-12 months after stopping
- Unprovoked VTE: ~10% recurrence at 1 year, ~30% at 5 years off anticoagulation
- Provoked by a major transient factor: ~3% at 5 years - the basis for stopping at 3 months
- Male sex carries ~1.5-2x the recurrence risk of female
Complications
- Post-thrombotic syndrome in 20-50% after proximal DVT - pain, oedema, hyperpigmentation, venous ulceration
- Compression stockings do not prevent it (SOX trial); early anticoagulation and avoiding recurrence do
- Chronic thromboembolic pulmonary hypertension (CTEPH) in ~2-4% after PE
- Persistent dyspnoea 3 months after PE -> echo, then V/Q scan (V/Q, not CTPA, is the screening test)
- Potentially curable by pulmonary endarterectomy - refer to a specialist centre
- Bleeding on anticoagulation: major bleeding ~1-3%/year, intracranial ~0.2-0.5%/year
- PE mortality: ~1-2% if haemodynamically stable, ~25-50% in high-risk PE
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