A deep vein thrombosis (DVT) refers to thrombus formation within the deep venous system. This commonly refers to the lower limbs but does not exclude the upper limbs. It is a form of venous thromboembolism (VTE) which is of great concern as it may lead to the other form of VTE - a pulmonary embolism (PE). The greatest risk of a PE is death. Therefore a DVT is a serious concern that needs to be managed appropriately.
🦴 Anatomy
The deep venous system refers to the veins that are located beneath the fascia and accompany the major arteries.
Let’s take a look at the deep venous system of the lower limb:
- The anterior tibial vein forms from penetrating branches from the dorsal venous arch.
- The posterior tibial vein as well as the fibular/peroneal vein arise from the lateral plantar veins.
- The popliteal vein forms as all three veins (anterior tibial, posterior tibial and fibular) unite.
- The popliteal vein then passes through the adductor hiatus and into the adductor canal into the thigh region where it is then referred to as the femoral vein.
- The deep femoral vein/profunda femoris vein is another deep vein of the thigh that forms from the unification of perforating veins in the thigh. It drains into the femoral vein as well.
- Once passing underneath the inguinal ligament femoral vein is then referred to as the external iliac vein.
- The inferior gluteal and superior gluteal veins drain the gluteal region and drain into the internal iliac vein.
Pathophysiology
Virchow’s triad describes the 3 major factors that contribute to formation of a thrombus:
- Stasis - stagnant blood is more likely to clot. Stasis may be due to long surgical operations, being bed bound, long journeys (such as plane journeys). The collagen also triggers the coagulatory cascade through which soluble fibrinogen is converted into insoluble fibrin which meshes together platelets to form a platelet plug which becomes a stable clot.
- Endothelial injury - endothelial injury may occur due to piercing of the vessel wall or due to shear stress that accompanies turbulent blood flow (for example in hypertensive states). Vessel injury exposes underlying endothelium and collagen. This exposed collagen binds to von Willebrand factor (vWF) that is released from the damaged endothelium. This then binds to the vWF receptors on platelets which promotes adhesion of the platelet.
- Hypercoagulability - changes to blood constitution that make the blood hypercoagulable. This may occur with hyperviscosity (for example in polycythaemic states), cancer, high-oestrogen levels (contraceptive use, HRT, obesity, pregnancy), sepsis, thrombophilias (such as Factor V Leidin).
⚠️ Risk factors
Generic risk factors for DVT:
- Increasing age
- Immobility
- Cancer
- Surgery
- Pregnancy
- Oestrogen therapy - oral contraceptive pill, HRT.
- Previous VTE
- Inherited thrombophilia - such as Factor V Leiden, prothrombin gene mutation, protein C and S deficiency, antithrombin deficiency, APLAS)
- Polycythaemia
- Dehydration
- Multiple pregnancy
- Pre-eclampsia
- C-section
- Prolonged labour
- Stillbirth
- Preterm birth
- Postpartum haemorrhage
- Hyperemesis gravidarum - leading to dehydration.
- Parity ≥3
- Age >35 years old
- IVF pregnancy
😷 Presentation
- Unilateral calf/thigh swelling and pain - the pain is localised to the deep venous system (groin → adductor canal → popliteal fossa). Very rarely is there bilateral DVTs. Pregnancy most commonly causes DVT within the proximal veins of the left leg. This is believed to be due to the uterus compressing the left common iliac vein by the gravid uterus.
This phenomenon is similar to a condition known as May-Thurner syndrome(or iliac vein compression syndrome or Cockett syndrome) which is when the left common iliac vein is compressed by the pressure from the right common iliac artery which leads to venous outflow obstruction → stasis of blood and subsequent DVT formation in the left leg.
It occurs in the left common iliac due to its path traversing the right common iliac which then compresses the vein against the lumbar spine.
- Redness
- Warmth or coolness of the affected limb
- Dilated superficial veins
- Unilateral/asymmetrical pitting oedema
The name translates to “painful blue inflammation”. It is essentially acute limb ischaemia that in fact originates in the venous system. It occurs due to complete occlusion of the vein which causes pressure build up and subsequent plasma leakage into the interstitium of the limb compartment → compartment syndrome and subsequent limb ischaemia as the arterial supply becomes compressed and compromised.
😷 Symptoms of PCD include:
- Cyanosis of affected limb
- Severe pain
- Paraesthesias
- Absent distant pulses
- Swelling of entire leg
- Bullae
- Paralysis
- Gangrene
- Cold limb
🧰 Management:
- It requires prompt recognition and management. The initial management must be started without waiting for results of the investigations. It involves anticoagulation with unfractionated heparin or low molecular weight heparin (LMWH) - enoxparin/dalteparin.
- Patients should also be immediately referred to vascular surgery for treatment. This could include catheter-directed thrombolysis or surgical thrombectomy, for example.
🔍 Investigations
We will take a look at diagnosis in non-pregnant patients first and foremost, followed by the investigations undertaken in pregnant patients as this differs:
Investigating a DVT in the non-pregnant patients:
If a DVT is suspected, a two-level Wells score should be calculated to estimate the probability of a DVT and guide further action:
Features | Points |
Active cancer - ongoing treatment, treated for in the past 6 months or palliative. | +1 |
Paralysis, paresis, plaster immobilisation of leg | +1 |
Recently bedbound for ≥3 days, major surgery within 12 weeks | +1 |
Localised pain along deep venous system or entire leg swollen | +1 |
Affected calf swollen at least 3cm more than asymptomatic calf* | +1 |
Unilateral pitting oedema | +1 |
Collateral superficial veins | +1 |
Previous DVT documented | +1 |
Alternative diagnosis as likely/more likely as DVT | -2 |
*When measuring the calf, we should measure the circumference of the leg 10cm below the tibial tuberosity on both legs and compare the size differences.
- Score ≥2 → DVT likely
- Proximal leg vein ultrasound to be done within 4 hours + patient should receive interim anti-coagulation:
- If positive → make diagnosis and start treatment.
- If negative → do D-dimer test
- If D-dimer is negative → consider alternative diagnosis.
- If D-dimer is positive → stop interim coagulation and repeat proximal leg vein ultrasound within 6-8 days.
- If the proximal leg vein ultrasound is not able to performed within 4 hours then → do D-dimer and offer interim anti-coagulation. The ultrasound should ultimately be done within 24 hours.
- Score ≤1 → DVT unlikely
- D-dimer test should be done within 4 hours.
- If positive → perform proximal leg vein ultrasound within 4 hours.
- If the proximal leg vein ultrasound is not able to performed within 4 hours then → do D-dimer and offer interim anti-coagulation. The ultrasound should ultimately be done within 24 hours.
- If negative → consider consider alternative diagnosis.
- If the D-dimer cannot be done within 4 hours then → offer interim anti-coagulation until the result is obtained.
Investigations for DVT in pregnant patients:
- If negative but a high level of clinical suspicion remains → repeat on days 3 and 7 and discontinue anticoagulation.
- If negative and there is a low level of clinical suspicion → discontinue anticoagulation.
💡 D-dimers are not useful in pregnancy and should not be done as pregnancy normally raises D-dimer values anyways. This is why we repeat the ultrasound instead of performing a D-dimer as we tend to do normally.
- Pregnancy
- Cancer
- Cardiac failure
- Pneumonia
- Post-operatively
NICE recommends immediate same-day assessment if a DVT is suspected in a pregnant woman/woman who has given birth in the past 6 weeks.
🧰 Management
Anti-coagulation is the mainstay of DVT management. NICE changes the guidelines in 2020 to favour the use of direct oral anti-coagulants (DOACs). However, if there are contrainidcations then low molecular weight heparin (LMWH) can be used. Otherwise, warfarin is the alternative.
Initial management:
As mentioned we need to start interim anticoagulation while waiting for results of the scans/tests. This is given in the form of DOACs or LMWH if contraindicated DOACs.
Patients beginning interim anticoagulation should have baseline bloods performed prior to initiation of treatment (FBC, U&Es, LFTs, PT and aPTT)
⚠️ In patients with iliofemoral DVT that is symptomatic for less than 14 days then catheter-directed thrombolysis is indicated.
Long-term management:
Let’s take a look at the options for long-term anticoagulation:
- 🥇 1st line - DOAC
- Apixaban or rivaroxaban
- 🥈 2nd line - if DOACs are not appropriate:
- LMWH (such as enoxaparin) followed by DOAC (specifically dabigatran/edoxaban) or warfarin.
- Active cancer - DOAC. This is a change in the guidelines as it was previously LMWH that was recommended.
- Pregnant - LMWH
- Enoxaparin
- Severe renal impairment - LMWH OR unfractionated heparin followed by warfarin
- Antiphospholipid syndrome - LMWH followed by warfarin
The duration of anticoagulation is dependent on the DVT being deemed as provoked or unprovoked:
- Provoked DVT - treatment is terminated after 3 months. However, if they have active cancer it may continue up until 6 months.
- Unprovoked DVT - treatment is continued up until 6 months. However, this also needs to be weighed against their risk of a bleed. Patients also need to be investigated for an unprovoked VTE if they are not continuing anticoagulation (for example, antiphospholipid antibody testing and assessing for hereditary thrombophilias if suspected).
🚨 Complications
- Pulmonary embolism - this is ultimately the biggest concern and can lead to subsequent death if not avoided and managed appropriately.
- Post-thrombotic syndrome - venous hypertension that leads to venous ulceration and it’s associated features (pain, swelling, lipodermatosclerosis, hyperpigmentation etc.). It is a form of chronic venous insufficiency secondary to DVT.
- Heparin-induced thromboyctopenia (HIT)
HIT is a potential adverse effect following heparin administration. It is caused by the formation of antibodies against complexes of platelet factor 4 (PF4) and heparin.
The antibodies bind to the PF4-heparin complexes and induce platelet activation → prothrombotic state. This uses up the platelets and results in thrombosis, >50% reduction in platelets (thrombocytopenia), and skin allergy.
Management includes:
- 🥇 Cessation of heparin and LMWH
- Start a direct thrombin inhibitor
- Argatroban
- Danaparoid or fondaparinux can be used as well.