DVT

management is from eTG 2024

Definition and Types

• VTE (Venous Thromboembolism) is a condition that involves blood clot formation within a vein, potentially causing serious health complications.
  • Deep Vein Thrombosis (DVT): A clot that forms in the deep veins, usually in the lower extremities.
    • Proximal DVT: Affects deep veins proximal to the knee, including the popliteal vein or more central veins.
    • Distal DVT: Affects deep veins below the knee.
  • Pulmonary Embolism (PE): Occurs when part of a clot dislodges and travels to the lungs, blocking blood flow.
  • Superficial Vein Thrombosis: Involves thrombus formation in superficial veins with inflammation. About 25% of cases have a concomitant DVT.

Clinical Significance

• VTE Complications:
  • Increased risk of recurrent VTE.
  • Post-thrombotic Syndrome (PTS): Chronic pain and swelling in the affected limb due to previous DVT.
  • Pulmonary Embolism: Can be fatal, particularly if untreated; early intervention is crucial.
  • VTE Recurrence: Risk factors include previous VTE, active cancer, immobility, and thrombophilia.

Symptoms

• Pain
• Swelling 
• Induration
• Erythema along the course of a superficial vein. 
• If erythema extends significantly beyond the vein: Cellulitis ? biopsy to confirm
• Vein can be palpated as a tender “cord” in superficial thrombophlebitis

Risk Factors

• Major (relative risk 5-20) – SLOMMP
  • Surgery – major abdominal/pelvic, hip/knee replacements, post ICU
  • Lower limb problems – #, varicose veins
  • Obstetrics – late pregnancy, C/S, puerperium
  • Malignancy – abdominal/pelvic, advanced/metastatic
  • Mobility – hospitalization, institutional care
  • Previous VTE
• Minor (relative risk 2-4) – COM
  • Cardiovascular – congenital heart disease, CHF, HT, superficial venous thrombosis, CVL
  • Oestrogens – OCP, HRT (Increased estrogen and progestin → increase in prothrombin and fibrinogen and a decrease in protein S)
  • Miscellaneous
    • COPD
    • neurological disability
    • occult malignancy
    • thrombotic disorder
    • long distance travel
    • obesity 
    • IBD
    • nephrotic syndrome – 
    • dialysis
    • myeloproliferative disorders
    • paroxysmal nocturnal haemoglobinuria
    • Bechet’s disease
• Thrombophillias 🡪 test in those < 50years with recurrent or a strong FHx
• Factor V Leiden mutation
• Prothombin gene mutation
• Hyperhomocysteinaemia
• Antiphospholipid antibody syndrome
• Deficiency of antithrombin III, protein C or protein S
• High concentrations of factor VIII or XI
• Increased lipoprotein (a)

Diagnosis of VTE

Clinical Prediction Tools

• Wells Criteria for DVT: Estimates the probability of DVT using risk factors like recent surgery, active cancer, or leg swelling.
• Wells Criteria for PE: Assesses risk based on symptoms like tachycardia, recent immobilization, or hemoptysis.
  • Active cancer – Treatment or palliation within 6 months
  • Bedridden recently >3 days or major surgery within 12 weeks
  • Calf swelling >3 cm compared to the other leg – Measured 10 cm below tibial tuberosity
  • Collateral (nonvaricose) superficial veins present
  • Entire leg swollen
  • Localized tenderness along the deep venous system
  • Pitting edema, confined to symptomatic leg
  • Paralysis, paresis, or recent plaster immobilization of the lower extremity
  • Previously documented DVT
  • Alternative diagnosis to DVT as likely or more likely
• Revised Geneva Score for PE: Uses clinical variables (age, heart rate, history of VTE) to assess PE risk.
• Pulmonary Embolism Rule-Out Criteria (PERC): For low-risk patients (<15% risk)
  • Age ≥50
  • HR ≥100
  • O₂ sat on room air <95%
  • Unilateral leg swelling
  • Hemoptysis
  • Recent surgery or trauma
  • Surgery or trauma ≤4 weeks ago requiring treatment with general anesthesia
  • Prior PE or DVT
  • Hormone use : Oral contraceptives, hormone replacement or estrogenic hormones use in males or female patients
• YEARS Algorithm: Combines clinical signs with D-dimer testing for suspected PE, especially useful for stable patients ≥18 years.
• Pregnancy-adapted YEARS Algorithm: Limited data for validation.

Diagnostic Imaging

• Compression Ultrasound: First-line imaging for DVT diagnosis.
  • Single negative ultrasound can exclude DVT.
  • Identify if the thrombus is in a deep or superficial vein
• CT Pulmonary Angiography (CTPA): Preferred diagnostic tool for PE.
  • High sensitivity and specificity.
  • Contraindicated in patients with severe allergies to contrast or impaired renal function.
• Ventilation/Perfusion (V/Q) Scan: Alternative to CTPA in pregnant patients or those requiring low radiation exposure.
• Cardiac Troponin: Assesses the severity of PE; elevated levels suggest a higher risk of mortality.

Treatment of VTE

Anticoagulant Therapy

• Prevents thrombus extension and reduces the risk of recurrence.
• Before Initiating Therapy, Collect baseline blood tests:
  • APTT
  • INR
  • full blood count
  • renal function
  • liver function
  • Beta hCG test for patients of childbearing potential.
• Types of Anticoagulants:
  • Direct-Acting Oral Anticoagulants (DOACs):
    • Preferred for most VTE cases.
    • Examples: Rivaroxaban, Apixaban, Edoxaban.
  • Warfarin:
    • Indicated in patients with contraindications to DOACs.
    • Preferred in patients with severe renal impairment or antiphospholipid syndrome.
    • Requires initial overlap with parenteral anticoagulant until INR therapeutic (2.0-3.0).
  • Parenteral Anticoagulants:
    • Low Molecular Weight Heparin (LMWH): Preferred for pregnant and breastfeeding patients.
    • Unfractionated Heparin: Choice for severe renal impairment or when rapid reversal is needed,
• Duration of Therapy:
  • Provoked VTE: Short duration (3-6 months) if a clear transient risk factor is identified (e.g., surgery).
  • Unprovoked VTE: Consider extended therapy (6-12 months or indefinite) if bleeding risk is low.
  • Cancer-Associated VTE: Extended duration, often for the duration of cancer activity or treatment.

 Suggested duration of anticoagulant therapy to treat acute venous thromboembolism

Clinical situation	Duration of therapy
Proximal DVT or PE that was unprovoked or associated with a transient (nonsurgical) risk factor DVT or PE associated with active cancer	3 to 6 months, followed by consideration of extended therapy
Proximal DVT or PE caused by major surgery or trauma that is no longer present	3 months
Distal DVT that was unprovoked	3 months
Distal DVT caused by a transient provoking factor	6 weeks
etg: Table 3.14 Suggested duration of anticoagulant therapy to treat acute venous thromboembolism

Management by Type

Region	Category	Veins
Lower Limbs	Deep Proximal	Common iliac vv. external iliac vv. internal iliac vv. common femoral vv. profunda femoris (deep femoral) vv. femoral vv. popliteal vv.
	Deep Distal	gastrocnemius vv. soleal vv. tibial (anterior and posterior) vv. peroneal vv.
	Superficial	Great saphenous vv. small saphenous vv. anterior accessory saphenous vv. intersaphenous vv.
Upper Limbs	Deep	Subclavian vv. axillary vv. brachial vv. ulnar vv. radial vv. interosseous vv.
	Superficial	Basilic vv. cephalic vv. median cubital vv. accessory cephalic vv. median veins of the forearm vv.

• Proximal DVT and PE:
  • Requires full anticoagulation unless contraindicated.
  • Thrombolysis or Interventional Therapy: Considered for hemodynamically unstable PE or severe symptomatic DVT
• Distal DVT:
  • Anticoagulation is favoured, but surveillance with serial ultrasounds is an option in low-risk patients,
  • Anticoagulant therapy typically for 6 weeks if no persistent risk factors
  • If untreated, about 15% extend to proximal veins
  • (Righini, M., Paris, S., Le Gal, G., Laroche, J. P., David, J. S., Perrier, A., Bounameaux, H. (2008). Clinical relevance of distal deep vein thrombosis. A systematic review. Journal of Thrombosis and Haemostasis, 6(5), 759-764. doi:10.1111/j.1538-7836.2008.02921.)
• Superficial Vein Thrombosis:
  • If significant, anticoagulation may be needed to prevent extension to deep veins – see below

VTE in Unusual Locations

Upper Limb DVT

• Axillary and Subclavian Vein Thrombosis:
  • 30% risk of associated PE.
  • Evaluate for thoracic outlet syndrome (compression due to extra rib or lesion).
  • Management: Standard anticoagulation; consider imaging for compression causes.

Splanchnic Vein Thrombosis

• Includes portal, mesenteric, and hepatic vein thrombosis (Budd-Chiari Syndrome).
  • Anticoagulate for 3-6 months.
  • Low molecular weight heparin, DOACs, or warfarin may be used, but consider liver function.

Other Rare Venous Thromboses

• Cerebral Vein Thrombosis, Gonadal Vein Thrombosis: Requires individualized management with specialist input.

Special Populations

• Post-thrombotic Syndrome (PTS):
  • Develops despite anticoagul
• Superficial Vein Thrombosis:
  • Risk of progression to VTE requires potential anticoagulation . see below
• Periprocedural Management:
  • Patients undergoing surgery while on anticoagulants require careful management:
    • Discontinue DOACs 1-2 days before minor surgery and 3-5 days before major surgery.
    • LMWH bridging for patients on warfarin may be required for high-risk patients.
• Palliative Care:
  • Individualized approach balancing risk of VTE, treatment burden, bleeding risk, and goals of care.
  • May involve using lower-intensity or shorter-duration anticoagulants if VTE is diagnosed.

Complications and Follow-Up

1. Post-Thrombotic Syndrome (PTS):
   • Chronic complication of DVT, characterized by pain, swelling, skin changes, and venous ulcers.
   • Encourage use of graduated compression stockings.
   • Early mobilization and exercise to prevent PTS.
2. Recurrent VTE:
   • Evaluate for persistent or recurrent risk factors.
   • Consider indefinite anticoagulation in high-risk patients, balancing bleeding risk.
3. Surveillance and Monitoring:
   • Regular follow-up to assess bleeding risk, adherence, and any need for adjusting anticoagulation therapy.
   • Periodic blood tests to monitor INR (for warfarin) or renal function (for DOACs).

DOACs for VTE Treatment

• Direct-acting oral anticoagulants (DOACs) target specific factors in the coagulation cascade, reducing the need for initial parenteral anticoagulation and avoiding routine monitoring.
• They are effective for treating venous thromboembolism (VTE) — including both deep vein thrombosis (DVT) and pulmonary embolism (PE).
• Monitoring
  • No routine monitoring required.
  • Periodically assess renal function, especially in elderly patients.
• Apixaban and Rivaroxaban: Preferred DOACs for VTE
• Apixaban and Rivaroxaban are Factor Xa inhibitors and are preferred over other anticoagulants like dabigatran and warfarin due to fewer monitoring requirements and a lower risk of major bleeding.
• Mechanism of Action
  • Factor Xa Inhibitors: Both Apixaban and Rivaroxaban inhibit Factor Xa, a key enzyme in the coagulation pathway that converts prothrombin to thrombin, thereby reducing clot formation.
  • Direct Thrombin Inhibitors: Dabigatran inhibits thrombin, which prevents the conversion of fibrinogen to fibrin.

Anticoagulant	Initial Therapy	Maintenance Therapy	Renal Function Considerations	Monitoring Requirements	Comments
Apixaban	10 mg orally, twice daily for 7 days	5 mg orally, twice daily	Avoid if CrCl < 25 mL/min	No routine monitoring needed	Preferred oral option; higher bleeding risk in menstrual periods
Rivaroxaban	15 mg orally, twice daily for 21 days	20 mg orally, once daily	Use with caution if CrCl 15-29 mL/min; avoid if CrCl < 15 mL/min	No routine monitoring needed	Preferred oral option; similar menstrual bleeding risk
Dabigatran	Parenteral anticoagulant for 5 days, then 150 mg orally, twice daily (younger than 75 and CrCl > 50 mL/min)	110 mg orally, twice daily if age ≥75 or CrCl 30-50 mL/min	Avoid if CrCl < 30 mL/min	No routine monitoring needed	Requires initial parenteral anticoagulation; limited data for obesity
Warfarin	Parenteral anticoagulant + warfarin (dose adjusted to INR 2-3)	Dose adjusted to maintain INR 2-3	Safe in severe kidney impairment	Regular INR monitoring required	Preferred in severe renal impairment and high-risk antiphospholipid syndrome
LMWH (e.g., Dalteparin, Enoxaparin)	Dalteparin: 200 units/kg once daily or 100 units/kg twice daily. Enoxaparin: 1.5 mg/kg once daily or 1 mg/kg twice daily	Dose maintained as per initial therapy	Adjust dosage in CrCl < 30 mL/min (seek expert advice)	No routine monitoring needed (except in renal impairment)	Preferred in pregnancy, breastfeeding, severe renal impairment
Unfractionated Heparin (UFH)	80 units/kg IV bolus, then 18 units/kg/hr IV infusion	Dose adjusted based on APTT	Safe in severe renal impairment	Intensive APTT monitoring required	Suitable for patients needing rapid reversal of anticoagulation

Dosing and Administration of DOACs

Apixaban

• Initial Dose:
  • 10 mg twice daily for 7 days.
• Maintenance Dose:
  • 5 mg twice daily after the initial period.
• Extended Therapy:
  • 2.5 mg twice daily for those who require long-term anticoagulation (e.g., for recurrent unprovoked VTE).
• Renal Function:
  • CrCl ≥ 25 mL/min: Safe to use.
  • CrCl < 25 mL/min: Contraindicated.
• Special Considerations:
  • Well-tolerated in elderly patients.
  • Reduced menstrual bleeding compared to rivaroxaban.
  • Can be used for extended therapy at a lower dose for recurrent VTE prevention.

Rivaroxaban

• Initial Dose:
  • 15 mg twice daily for 21 days.
• Maintenance Dose:
  • 20 mg once daily after the initial period.
• Extended Therapy:
  • 10 mg once daily for those needing long-term therapy.
• Renal Function:
  • CrCl ≥ 30 mL/min: Full dosing.
  • CrCl 15-29 mL/min: Specialist guidance needed.
  • CrCl < 15 mL/min: Contraindicated.
• Special Considerations:
  • Once-daily maintenance dosing may improve adherence.
  • Higher rates of menstrual bleeding than other DOACs.
  • Food intake increases absorption; recommended to be taken with food during the initial 3-week high-dose period.

Dabigatran

• Alternative DOAC for VTE
• Mechanism of Action: Direct Thrombin Inhibitor: Prevents the conversion of fibrinogen to fibrin, reducing thrombus formation.

Dosing:

• Requires initial parenteral anticoagulation (e.g., LMWH) for 5 days before transitioning to oral dabigatran.
• Dosage After Parenteral Anticoagulation:
  • Patients < 75 years:
    • CrCl > 50 mL/min: 150 mg twice daily.
    • CrCl 30-50 mL/min: 110 mg twice daily (or if at high bleeding risk).
  • Patients ≥ 75 years:
    • CrCl > 30 mL/min: 110 mg twice daily.
• Renal Function:
  • Contraindicated if CrCl < 30 mL/min.

Special Considerations:

• Not recommended for patients with mechanical heart valves.
• Dose adjustments may be necessary for high bleeding risk populations.

Warfarin: Vitamin K Antagonist for VTE

• Inhibits the synthesis of Vitamin K-dependent clotting factors (II, VII, IX, X), reducing thrombus formation.

Dosing:

• Requires overlap with parenteral anticoagulation (LMWH or UFH) for a minimum of 5 days.
• Initial Dosing:
  • Use a local protocol or:
    • Start with 5 mg to 10 mg daily, adjusting to maintain an INR of 2.0-3.0.
• Monitoring:
  • Requires frequent INR monitoring until stabilized.
  • Dose adjustments based on INR readings.

Special Considerations:

• Preferred in patients with severe renal impairment.
• Contraindicated in pregnancy (teratogenic), but can be used during breastfeeding.
• Warfarin is sensitive to dietary vitamin K; consistency in intake is crucial.

Low Molecular Weight Heparin (LMWH)

• Common Agents: Enoxaparin, Dalteparin.
• Preferred in pregnancy, breastfeeding, and patients with active cancer.

Dosing:

• Enoxaparin:
  • CrCl ≥ 30 mL/min: 1.5 mg/kg once daily or 1 mg/kg twice daily.
  • CrCl < 30 mL/min: 1 mg/kg once daily.
• Dalteparin:
  • 200 units/kg once daily or 100 units/kg twice daily.

Unfractionated Heparin (UFH)

• Used in patients with severe renal impairment or those at high bleeding risk.

Dosing:

• Loading Dose: 80 units/kg IV.
• Maintenance: 18 units/kg/hour infusion, adjusted to target APTT.

Fondaparinux

• Suitable for patients with heparin-induced thrombocytopenia (HIT).

Dosing:

• 2.5 mg once daily for prophylaxis.
• Use caution in elderly or low-weight patients.

Duration of Anticoagulant Therapy for VTE

1. Short-Term (3-6 Months)

• For provoked VTE with a transient risk factor (e.g., surgery, immobilization).

2. Extended Therapy (Beyond 6 Months)

• For unprovoked VTE, particularly if recurrence risk is high.
• For VTE associated with active cancer (until cancer is no longer active).

3. Indefinite Therapy

• For patients with high-risk thrombophilias (e.g., antiphospholipid syndrome).
• For those with recurrent unprovoked VTE.

Extended Therapy Options

Low-Intensity DOACs

• Apixaban: 2.5 mg twice daily.
• Rivaroxaban: 10 mg once daily.
• Reassess bleeding vs. recurrence risk periodically.

Aspirin as an Alternative

• Low-Dose Aspirin (100 mg daily): For patients who are not candidates for extended DOAC therapy.

Management of Bleeding with DOACs

Bleeding Risks and Mitigation:

• Monitor renal function periodically.
• For high-risk bleeding populations (e.g., elderly, those with liver impairment), consider lower doses.

Specific Reversal Agents:

• Andexanet Alfa: Reverses effects of Factor Xa inhibitors (Apixaban, Rivaroxaban).
• Idarucizumab: Reverses effects of Dabigatran.

Special Populations

Pregnancy and Breastfeeding

• Preferred agents: LMWH (e.g., Enoxaparin, Dalteparin).
• Avoid DOACs due to insufficient safety data.

Active Cancer

• Preferred agents: LMWH, Apixaban, Rivaroxaban.
• Avoid DOACs in patients with unoperated gastrointestinal or genitourinary cancers.

Renal Impairment

• Mild to Moderate Impairment: Adjust dosing of DOACs based on CrCl.
• Severe Impairment (CrCl < 30 mL/min): Use UFH or warfarin.

Superficial Vein Thrombosis Management

• Overview
  • Superficial vein thrombosis (SVT) involves a thrombus forming in a superficial vein, causing vessel wall inflammation.
  • Often self-limiting but can lead to complications like VTE (DVT or PE) or thrombus extension, especially if risk factors (e.g., cancer, pregnancy) are present.
  • Common associations: intravenous cannulation, pregnancy, active cancer, varicose veins, venous stasis, or trauma.
• Diagnosis:
  • Compression ultrasound is suggested, especially for those with VTE risk factors.
  • Ultrasound determines thrombus length, proximity to deep veins, and excludes concurrent DVT.
  • Approximately 25% of SVT cases have concomitant DVT.
• Management:
• Depends on the risk of extension to DVT or PE
  • Proximity to deep veins (less than 3 cm away).
  • Length of the thrombus (greater than 5 cm).
  • Presence of active cancer, recent surgery, or immobility.
  • History of previous VTE or known thrombophilia.
• other managements include:
  • heat
  • elevation
  • NSAIDs
  • compression stockings
  • IV catheter? if so removed
  • Antibiotic therapy if SSx of infection (high fever/purulent drainage)
• Both low molecular weight heparin (LMWH) and NSAIDs reduce the incidence of extension or recurrence of superficial thrombophlebitis by about 70% compared with placebo
  • (Decousus, H., Quéré, I., Presles, E., Becker, F., Barrellier, M. T., Couturaud, F., … & Leizorovicz, A. (2010). Superficial thrombophlebitis and venous thromboembolism: a large, prospective epidemiologic study. Annals of Internal Medicine, 152(4), 218-224. doi:10.7326/0003-4819-152-4-201002160-00006)
• NOACs are not the first-line recommendation for isolated superficial thrombophlebitis, they are considered a reasonable alternative, especially when the risk of thrombus extension into deep veins exists.
• Rivaroxaban and apixaban have been used off-label for this purpose, especially in cases where LMWH or fondaparinux is not suitable

as per eTG 2024 :

Risk Level	Criteria	Treatment
Low-Risk Superficial Vein Thrombosis	– Related to intravenous cannulation. – More than 3 cm from the deep venous system. – Thrombus is shorter than 5 cm. – No other VTE risk factors.	– No anticoagulants needed. – Symptomatic care: Topical/oral NSAIDs for 7-14 days. – Optimize VTE prophylaxis in predisposing situations (e.g., hospitalization).
Intermediate-Risk Superficial Vein Thrombosis	– More than 3 cm from the deep venous system. – Thrombus length greater than 5 cm.	– Anticoagulant therapy is optional. – Suitable Regimens: • Dalteparin: 5,000-10,000 units SC daily for 45 days (CrCl ≥30 mL/min). • Enoxaparin: – CrCl ≥30 mL/min: 40-80 mg SC daily for 45 days. – CrCl <30 mL/min: 20 mg SC daily for 45 days. • Fondaparinux: 2.5 mg SC daily for 45 days (CrCl >50 mL/min). • Rivaroxaban: 10 mg orally daily for 45 days (CrCl ≥30 mL/min). – Consult specialists for dosing adjustments if CrCl is below recommended thresholds.
High-Risk Superficial Vein Thrombosis	– Thrombus extends to within 3 cm of the deep venous system. – Propagation of thrombus despite intermediate-risk anticoagulation therapy.	– Use anticoagulants for 3 months. – Suitable Options: • Direct-acting oral anticoagulants (DOACs). • Warfarin. • Parenteral anticoagulants.