Disorders of coagulation or thrombosis - venous thromboembolic events, such as deep vein thrombosis and pulmonary embolism and complications
Description
- DVT and PE are one disease - ~50% of proximal DVT have asymptomatic PE
- Proximal DVT = popliteal or above. Distal (calf) = below
- Only proximal DVT reliably embolises; isolated distal DVT may be surveilled rather than anticoagulated
- Unusual sites: cerebral venous sinus, splanchnic, upper limb (catheter- or thoracic-outlet-related)
Provocation - determines duration of therapy, not initial treatment
| Examples | Recurrence after stopping | |
|---|---|---|
| Major transient | Surgery >30 min under GA, immobility >=3 days, caesarean | ~3%/yr |
| Minor transient | Oestrogen, pregnancy, long-haul flight, minor surgery, leg injury | ~5%/yr |
| Unprovoked | Nothing identified | ~10% at 1 yr, ~30% at 5 yr |
| Persistent | Active cancer, antiphospholipid syndrome, IBD | Highest |
Epidemiology
- Incidence 1-2 per 1,000/yr, doubling each decade after 40
- ~17,000 Australians/yr; hospital-associated VTE accounts for over half and is the commonest preventable cause of hospital death
- Recurrence risk highest in the first year after stopping anticoagulation
Combined oral contraceptive - risk by progestogen
| Progestogen | Approx OR |
|---|---|
| Drospirenone | ~7.9 |
| Cyproterone acetate | ~6.7 |
| Desogestrel/gestodene | ~5.6 |
| Levonorgestrel | ~3 (lowest-risk COC) |
- Absolute risk still low, but rises steeply with age; progestogen-only and IUD do not carry the risk
Aetiopathogenesis
- Virchow's triad - stasis, endothelial injury, hypercoagulability
- Thrombus initiates in valve pockets (low shear, hypoxia) -> red cell- and fibrin-rich (contrast platelet-rich arterial thrombus)
- This is why anticoagulants, not antiplatelets, are the treatment
Acquired risk factors
- Surgery (esp. orthopaedic, pelvic, neurosurgery), trauma, immobility, hospitalisation
- Active cancer - highest with pancreas, stomach, brain, lung, ovary, myeloproliferative neoplasms
- Tissue factor-bearing microparticles, mucin, cytokines; plus catheters and chemotherapy
- Oestrogen - COC, HRT, tamoxifen; pregnancy and puerperium (highest in the 6 weeks post-partum)
- Antiphospholipid syndrome, nephrotic syndrome, IBD, PNH, HIT, obesity, smoking, long-haul travel
- Central venous catheters, IV drug use
Inherited thrombophilia
- Factor V Leiden (~5% of Caucasians) and prothrombin G20210A - common, weak, little effect on recurrence risk
- Antithrombin, protein C, protein S deficiency - rare, strong, do raise recurrence risk
- Testing rarely changes management - see thrombophilia
Diagnosis
Clinical features of PE
| Symptom | Sign | ||
|---|---|---|---|
| Dyspnoea | 73% | Tachypnoea | 70% |
| Pleuritic chest pain | 66% | Crepitations | 51% |
| Cough | 37% | Tachycardia | 30% |
| Haemoptysis | 13% | S4 / loud P2 | ~24% |
| Circulatory collapse | 8% |
- ECG: sinus tachycardia commonest; S1Q3T3 and right axis are neither sensitive nor specific; anterior T-wave inversion V1-V4 correlates with RV strain
- Hypoxia and a raised A-a gradient are common but a normal SpO2 does not exclude PE
Pathway
1. Pre-test probability first - Wells (DVT and PE), Geneva; PERC to avoid testing altogether in a very-low-risk patient
2. D-dimer if low/intermediate probability - age-adjusted cutoff (age x 10 microg/L if >50) or YEARS algorithm
- High specificity in the young; near-useless in inpatients, cancer, pregnancy, post-op
3. Imaging
- DVT: whole-leg or proximal compression ultrasound (repeat at 1 week if negative and probability high)
- PE: CTPA; V/Q or V/Q SPECT if renal impairment, contrast allergy, or pregnancy
- Echo in the unstable patient: RV dilatation, McConnell's sign, D-shaped septum - enough to justify reperfusion when CTPA is unsafe
Severity - 2026 AHA/ACC Clinical Categories (A-E)
*"Massive" and "submassive" are retired, and so is anatomical clot burden as a severity measure*
| Definition | |
|---|---|
| A | Subclinical - incidental, asymptomatic |
| B | Symptomatic, low scores (PESI I-II, sPESI 0, Hestia 0) |
| C | Symptomatic, elevated scores (PESI III-V, sPESI >=1, Hestia >=1)<br>C1 normal RV + normal biomarkers; C2 RV dysfunction or raised biomarkers; C3 both |
| D | Incipient failure - normotensive shock, rising lactate/creatinine. D1 mild, D2 moderate-severe end-organ dysfunction |
| E | Cardiopulmonary failure. E1 persistent hypotension/cardiogenic shock; E2 refractory shock or arrest |
- A respiratory modifier (R) is appended for hypoxia or escalating oxygen requirement
- PE Response Team activation is Class 1 for categories C-E
Management
A. Anticoagulation - everyone
- DOAC preferred over warfarin unless contraindicated (lower recurrence-adjusted bleeding)
- Apixaban 10 mg bd x 7 days -> 5 mg bd
- Rivaroxaban 15 mg bd x 21 days -> 20 mg daily (with food)
- Dabigatran and edoxaban require 5 days of LMWH lead-in
- DOACs contraindicated: antiphospholipid syndrome (esp. triple-positive), mechanical valve, pregnancy/breastfeeding, CrCl <15-30, significant drug interactions (rifampicin, azoles, HIV protease inhibitors)
- LMWH preferred in pregnancy, and initially in severe renal failure (use UFH) and cancer with high bleeding risk
- If parenteral therapy needed: LMWH over unfractionated heparin
B. By clinical category
| Category | Management |
|---|---|
| A-B | Outpatient anticoagulation - validated by Hestia/sPESI; ensure follow-up |
| C1-C2 | Admit, anticoagulate. *Systemic thrombolysis is harmful here* |
| C3 | Admit, monitor closely. Reperfusion role unproven |
| D1-D2 | Advanced therapies may be considered; PERT |
| E1 | Systemic thrombolysis, catheter-directed lysis, mechanical thrombectomy or surgical embolectomy all reasonable |
| E2 | Systemic thrombolysis reasonable; ECMO as bridge. Surgical embolectomy not preferred |
- Alteplase 100 mg over 2 h (or 0.6 mg/kg over 15 min in arrest); absolute contraindications - prior intracranial haemorrhage, ischaemic stroke <3 months, intracranial neoplasm, active bleeding, recent head trauma/neurosurgery
- IVC filter only when anticoagulation is absolutely contraindicated - retrieve as soon as possible; no mortality benefit and it increases DVT
C. Duration - the real decision
- All patients: at least 3 months
- Stop at 3 months if provoked by a major transient risk factor
- Indefinite if:
- Unprovoked PE or proximal DVT (particularly a second event)
- Active cancer, antiphospholipid syndrome, antithrombin/protein C/protein S deficiency
- Recurrent VTE not related to a major transient factor
- Extended phase uses reduced-dose DOAC - apixaban 2.5 mg bd or rivaroxaban 10 mg daily after the first 6 months
- *Preferred over aspirin or nothing*
- Supporting extension: positive D-dimer after stopping, extensive thrombus (>5 cm, multiple veins, >7 mm diameter), proximal extension, inpatient at diagnosis, male sex, prior VTE
- Men after a first unprovoked event: recurrence high -> generally indefinite
- Women: HERDOO2 may identify those who can safely stop (Hyperpigmentation/oedema/redness, D-dimer >=250 while on treatment, Obesity BMI >=30, Older >=65 - score 0-1 -> can stop)
- Reassess bleeding risk and the decision annually, not once
D. Special situations
- Cancer-associated thrombosis
- Edoxaban or rivaroxaban if bleeding risk acceptable; apixaban also used
- LMWH (enoxaparin) instead if high GI bleeding risk: luminal GI cancer with primary in situ, other high GI bleeding risk, urinary tract cancer or nephrostomy
- Continue while cancer is active or on treatment
- VTE on the combined pill: anticoagulate; *do not stop the COC while anticoagulated - stop it at least 1 month before* ceasing anticoagulation (withdrawal bleeding, and rebound risk)
- Pregnancy/planned pregnancy: LMWH throughout pregnancy and post-partum; warfarin teratogenic, DOACs contraindicated. Intensity by risk profile
- Isolated distal DVT: serial ultrasound over 2 weeks, or anticoagulate 6 weeks-3 months if symptomatic, extensive, or in axial rather than muscular calf veins
- Superficial vein thrombosis >=5 cm or within 3 cm of the saphenofemoral junction -> fondaparinux 2.5 mg daily 45 days
- HIT: stop all heparin, non-heparin anticoagulant (argatroban, danaparoid, bivalirudin, or a DOAC once platelets recover). Never give platelets or start warfarin while thrombocytopenic
E. Prevention
- Risk-assess every hospital inpatient - the single largest opportunity
- Enoxaparin 40 mg daily (or 20 mg if CrCl 15-30), or mechanical prophylaxis if bleeding risk
- Extended prophylaxis after hip/knee arthroplasty and major abdominal cancer surgery
Associations
- Antiphospholipid syndrome, inherited thrombophilia
- Occult cancer - ~5-10% after unprovoked VTE; age-appropriate screening and a good history/examination only - extensive CT screening does not improve outcomes
- Myeloproliferative neoplasms and JAK2 mutation - especially splanchnic vein thrombosis
- PNH - unexplained thrombosis at unusual sites with haemolysis
- Nephrotic syndrome, IBD, Behcet disease, HIT, heparin and other drug reactions
- COVID-19 and other acute inflammatory states
- May-Thurner (left iliac vein compression), thoracic outlet syndrome (Paget-Schroetter)
Natural history & complications
- Recurrence risk is greatest in the first year after stopping, then falls but never to zero
- Case fatality of acute PE ~2% treated; higher with haemodynamic compromise
Predictors of recurrence
- Strong: unprovoked event, prior VTE, PE or proximal DVT, persistent risk factor (cancer, antiphospholipid syndrome), antithrombin/protein C/protein S deficiency
- Moderate: non-surgical provoking factor, male sex, raised D-dimer after stopping
- *Little or no effect: factor V Leiden, prothrombin G20210A, residual thrombus on imaging*
Complications
- Post-thrombotic syndrome ~20-50% after proximal DVT - pain, oedema, hyperpigmentation, venous ulceration
- Risk: proximal/extensive thrombus, recurrence, obesity, poor early anticoagulation control
- Graduated compression stockings do not prevent it (SOX trial) - use them for symptom relief only
- CTEPH ~2-4% after PE - persistent dyspnoea beyond 3 months -> V/Q scan (not CTPA - it misses distal disease) -> refer for pulmonary endarterectomy assessment
- Bleeding on anticoagulation - major bleeding ~1-3%/yr, intracranial ~0.2-0.4%/yr
- Recurrent PE, RV failure, chronic venous insufficiency
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