deep vein thrombosis

Venous Stasis & Hypercoagulability

Obstructive thrombus formation in the deep veins (usually lower extremity) carrying significant risk of pulmonary embolism and post-thrombotic syndrome.

pathophysiology

• Virchow’s Triad:
  1. Stasis: Immobility, paresis, anaesthesia.
  2. Endothelial Injury: Trauma, surgery, central lines.
  3. Hypercoagulability: Malignancy, pregnancy, Factor V Leiden, oestrogen use.
• Anatomy:
  • Deep Veins: Peroneal, Anterior/Posterior Tibial, Popliteal, Femoral, Iliac.

  • nomenclature trap

  • The “Superficial Femoral Vein” is a DEEP vein.

  • A clot here is a 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 is mandatory.

pre-test probability

Use Wells Score for DVT to stratify risk.

• Caveat: Wells score performs poorly in hospitalised/inpatients; maintain a lower threshold for ultrasound.

Score	Probability	Strategy
$\le$ 1	Low	D-dimer
$\ge$ 2	High	Compression Ultrasound (CUS)

diagnostic algorithm

1. Low PTP (Wells $\le$ 1):

   • Order D-dimer (highly sensitive).
   • Negative: DVT excluded.
   • Positive: Proceed to CUS.

   • clinical pearl

   • Use Age-Adjusted D-dimer for patients >50 years:

   • $Cutoff=Age\times 10\mu g/L$

2. High PTP (Wells $\ge$ 2):

   • Proceed directly to Proximal CUS.
   • If CUS negative but suspicion remains high $\to$ repeat CUS in 5-7 days or consider whole-leg US.

management: pharmacotherapy

evidence: cobrra trial (isth 2025 abstract)

Apixaban vs. Rivaroxaban for Acute VTE (RCT, n=2760)

• Status: Presented at ISTH 2025; final publication pending.
• Safety: Apixaban had significantly less bleeding (3.0% vs 6.7%).
• NNT: Treat ~27 patients with Apixaban to prevent 1 clinically relevant bleed.
• Efficacy: Identical recurrence rates (1.0% vs 1.0%).
• Impact: Suggests Apixaban is the preferred agent for acute VTE.

• 1. Direct Oral Anticoagulants (DOACs):
  • Apixaban (Preferred): 10 mg PO BID $\times$ 7 days $\to$ 5 mg PO BID.
  • Rivaroxaban: 15 mg PO BID $\times$ 21 days $\to$ 20 mg PO daily (must take with food).
  • Obesity: Guidelines support both agents for high BMI, though some experts prefer Rivaroxaban for >120kg due to specific PK data.
• 2. LMWH (Dalteparin/Enoxaparin):
  • Indications: Pregnancy, severe liver disease (Child-Pugh C), severe malabsorption.
  • Note: DOACs now accepted for most cancer VTE (non-GI/GU malignancies).
• 3. Warfarin:
  • Indications: Severe renal failure ($CrCl<15-30$), Antiphospholipid Syndrome (Triple positive), Mechanical Valves.

doac contraindications

• Pregnancy/Breastfeeding: Absolute contraindication.
• Antiphospholipid Syndrome: Avoid (esp. Triple Positive/Arterial).
• Liver Failure: Avoid in Child-Pugh B/C.
• Thrombocytopenia: Contraindicated if Platelets < 50 x $10^9$/L (Slide 8). 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” to Transient vs. Persistent risk factors.

Risk Category	Clinical Context	Duration	Notes
Transient (Reversible)	Surgery, trauma, immobilization, OCPs (if stopped).	3 months	Recurrence risk low (~3% in 5y).
Persistent (Irreversible)	Active cancer, IBD, autoimmune disease.	Indefinite	Continue as long as risk factor persists.
Unprovoked	No identifiable trigger.	Indefinite	Recurrence risk high (~30% in 5y). Reassess annually.
Isolated Distal DVT	Calf veins only.	Surveillance vs. 3 mo	Serial US for 2 weeks. Treat if severe symptoms or extension occurs.

long-term extension (>6 months)

evidence update: api-cat & renove (2025)

Question: Can we dose reduce “High Risk” or “Cancer” patients after 6 months?

• API-CAT (Active Cancer): Reduced dose (Apix 2.5 BID) was Non-Inferior to full dose for recurrence and safer for bleeding. $\to$ Dose reduce.
• RENOVE (Chronic/Unprovoked): Reduced dose was Safer (less bleeding) but did NOT meet non-inferiority for recurrence.
• Bottom Line: Dose reduction is standard for cancer (API-CAT). For high-risk unprovoked VTE (RENOVE), dose reduction is a trade-off (less bleeding risk vs. potentially higher recurrence risk).

hypercoagulability workup

choosing wisely: do not test acutely

Do NOT order a “Thrombophilia Screen” in the acute setting.

• Acute Phase: Active clotting consumes Protein C/S/Antithrombin $\to$ false positives (low levels).
• Anticoagulation: Heparin/DOACs interfere with Lupus Anticoagulant and protein assays.
• Indication: Only test if results will change management (e.g., stopping AC in a young patient with unprovoked DVT).
• Timing: Wait >2 weeks after stopping anticoagulation.
• Exceptions: Genetic PCR tests (Factor V Leiden, Prothrombin gene) can be done acutely but rarely change immediate management.

pregnancy & post-partum

VTE is a leading cause of maternal mortality. Hypercoagulability is physiological (evolutionary protection against haemorrhage).

exam trap

D-dimer is useless in pregnancy. It is physiologically elevated. Wells Score is NOT validated in pregnancy. Strategy: If clinical suspicion exists $\to$ CUS.

diagnosis in pregnancy

• Anatomy: Left-sided DVT is far more common ($>80\%$) due to compression of left iliac vein by right iliac artery and gravid uterus (May-Thurner physiology).
• Imaging:
  1. Compression Ultrasound (CUS).
  2. If CUS negative but high suspicion (esp. for isolated iliac DVT causing back/flank pain): Doppler of iliac veins or MRV. Avoid CT if possible.

management in pregnancy

• Drug of Choice: LMWH (Dalteparin, Tinzaparin, Enoxaparin).
  • Does not cross placenta.
  • Dosing: Weight-based therapeutic dosing.
  • Monitoring: Anti-Xa levels not routinely required (except extreme obesity or renal insufficiency).
• Contraindications:
  • DOACs: Cross placenta; risk of fetotoxicity. Avoid.
  • Warfarin: Teratogenic (embryopathy, CNS defects). Avoid (exception: mechanical valves in specialised centres).

peripartum & breastfeeding

• Labour:
  • Therapeutic LMWH: Hold 24h prior to induction or neuraxial anaesthesia (epidural).
  • Prophylactic LMWH: Hold 12h prior.
• Post-Partum Duration:
  • Treat for minimum 3 months total, including at least 6 weeks post-partum.
• Breastfeeding:
  • LMWH: Safe.
  • Warfarin: Safe (does not pass into breast milk).
  • DOACs: Unsafe (excreted in milk).

related pages: Pulmonary Embolism, Warfarin, Hereditary Thrombophilia, Superficial Vein Thrombosis