deep vein thrombosis
Contents
Obstructive thrombus formation in the deep veins (usually lower extremity) carrying significant risk of Pulmonary Embolism and post-thrombotic syndrome. Diagnosis requires objective testing — clinical signs are non-specific. DOACs (apixaban preferred) are first-line for most patients; LMWH for pregnancy, severe liver disease, or severe malabsorption.
pathophysiology
-
Virchow’s triad:
- Stasis — immobility, paresis, anaesthesia
- Endothelial injury — trauma, surgery, central lines
- Hypercoagulability — malignancy, pregnancy, Factor V Leiden, oestrogen use
-
Anatomy:
- deep veins: peroneal, anterior/posterior tibial, popliteal, femoral, iliac
The “superficial femoral vein” is a deep vein. A clot here = proximal DVT requiring full anticoagulation. True superficial veins: greater/lesser saphenous, basilic, cephalic.
diagnosis
Clinical signs (unilateral oedema, calf pain) are non-specific → objective testing mandatory.
pre-test probability
Use Wells Score for DVT to stratify risk.
- Wells score performs poorly in hospitalised patients — lower threshold for ultrasound
| Score | Probability | Strategy |
|---|---|---|
| ≤1 | Low | D-dimer |
| ≥2 | High | Compression ultrasound (CUS) |
diagnostic algorithm
Low PTP (Wells ≤1):
- Order D-dimer (highly sensitive)
- Negative → DVT excluded
- Positive → proceed to CUS
For patients >50 years: cutoff = age × 10 µg/L. Improves specificity without sacrificing sensitivity.
High PTP (Wells ≥2):
- Proceed directly to proximal CUS
- CUS negative but suspicion remains high → repeat CUS in 5–7 days or whole-leg US
management
pharmacotherapy
1. Direct oral anticoagulants (DOACs):
- Apixaban (preferred): 10 mg PO BID × 7 days → 5 mg PO BID
- Rivaroxaban: 15 mg PO BID × 21 days → 20 mg PO daily (must take with food)
- Obesity: guidelines support both agents for high BMI; some experts prefer rivaroxaban for >120 kg due to specific PK data
COBRRA (2026) — apixaban vs. rivaroxaban for acute VTE RCT, n=2760.
- Safety: apixaban had significantly less clinically relevant bleeding (3.3% vs 7.1%; major bleeding 0.4% vs 2.4%)
- Efficacy: identical recurrence rates (1.0% vs 1.0%)
- Supports apixaban as the preferred DOAC for acute VTE
2. LMWH (dalteparin/enoxaparin):
- Indications: pregnancy, severe liver disease (Child-Pugh C), severe malabsorption
- DOACs now accepted for most cancer VTE (non-GI/GU malignancies)
3. Warfarin:
- Indications: severe renal failure (CrCl <15–30 mL/min), Antiphospholipid Syndrome (triple positive), mechanical valves
- Pregnancy/breastfeeding — absolute contraindication
- Antiphospholipid Syndrome — avoid (especially triple positive/arterial)
- Liver failure — avoid in Child-Pugh B/C
- Thrombocytopenia — contraindicated if platelets <50 × 10⁹/L → consult haematology
- Drug interactions — paxlovid (nirmatrelvir/ritonavir), phenytoin, carbamazepine, azoles
- Bariatric surgery — absorption unreliable → use LMWH or warfarin
duration of therapy
Shift from “provoked/unprovoked” → transient vs. persistent risk factors.
| Risk Category | Clinical Context | Duration | Notes |
|---|---|---|---|
| Transient (reversible) | Surgery, trauma, immobilisation, OCPs (if stopped) | 3 months | Recurrence risk low (~3% in 5 years) |
| Persistent (irreversible) | Active cancer, IBD, autoimmune disease | Indefinite | Continue as long as risk factor persists |
| Unprovoked | No identifiable trigger | Indefinite | Recurrence risk ~30% in 5 years; reassess annually |
| Isolated distal DVT | Calf veins only | Surveillance vs. 3 months | Serial US for 2 weeks; treat if severe symptoms or extension |
long-term extension (>6 months)
- API-CAT (2025) — active cancer: reduced dose (apixaban 2.5 mg BID) non-inferior to full dose for recurrence and safer for bleeding → dose reduce
- RENOVE (2025) — high-risk VTE (unprovoked, recurrent, persistent risk factors), n=2768, median follow-up 37 months: reduced dose did not meet non-inferiority for recurrence (2.2% vs 1.8% at 5 years; HR 1.32 [0.67–2.60]) but significantly less clinically relevant bleeding (9.9% vs 15.2%; HR 0.61)
- Bottom line: dose reduction is standard for cancer (API-CAT). For high-risk non-cancer VTE, dose reduction = trade-off — low absolute recurrence in both groups but non-inferiority not proven.
what NOT to do
- Do not order a “thrombophilia screen” in the acute setting — active clotting consumes Protein C/S/antithrombin → false positives; anticoagulation interferes with lupus anticoagulant assays
- Do not test thrombophilia unless results will change management (e.g. stopping AC in a young patient with unprovoked DVT)
- Timing: wait >2 weeks after stopping anticoagulation
- Exception: genetic PCR tests (Factor V Leiden, Prothrombin gene) can be done acutely but rarely change immediate management
special populations
pregnancy and post-partum
VTE is a leading cause of maternal mortality. Hypercoagulability is physiological (evolutionary protection against haemorrhage).
D-dimer is physiologically elevated in pregnancy → useless for exclusion. Wells score is not validated in pregnancy. If clinical suspicion → proceed directly to CUS.
Anatomy: left-sided DVT far more common (>80%) — compression of left iliac vein by right iliac artery and gravid uterus (May-Thurner physiology).
Imaging:
- Compression ultrasound (CUS)
- CUS negative but high suspicion (especially isolated iliac DVT → back/flank pain): doppler of iliac veins or MRV. Avoid CT if possible.
Management:
- Drug of choice: LMWH (dalteparin, tinzaparin, enoxaparin)
- Does not cross placenta
- Weight-based therapeutic dosing
- Anti-Xa levels not routinely required (except extreme obesity or renal insufficiency)
- DOACs: cross placenta, risk of fetotoxicity → avoid
- Warfarin: teratogenic (embryopathy, CNS defects) → avoid (exception: mechanical valves in specialised centres)
Peripartum:
- Therapeutic LMWH: hold 24 hours prior to induction or neuraxial anaesthesia
- Prophylactic LMWH: hold 12 hours prior
Post-partum:
- Minimum 3 months total anticoagulation, including ≥6 weeks post-partum
- Breastfeeding: LMWH ✓ | Warfarin ✓ | DOACs ✗ (excreted in milk)
key trials summary
| Trial | Year | N | Intervention | Result |
|---|---|---|---|---|
| COBRRA (2026) | 2026 | 2760 | Apixaban vs. rivaroxaban, acute VTE | Equal efficacy; apixaban significantly less clinically relevant bleeding (3.3% vs 7.1%) |
| API-CAT (2025) | 2025 | — | Reduced vs. full-dose apixaban, cancer VTE >6 months | Non-inferior recurrence, less bleeding → dose reduce |
| RENOVE (2025) | 2025 | 2768 | Reduced vs. full-dose DOAC, high-risk VTE >6 months | Did not meet non-inferiority for recurrence (2.2% vs 1.8%); significantly less bleeding (9.9% vs 15.2%) |