Deep Vein Thrombosis Flashcards
Define DVT.
The development of a blood clot in a major vein deep to the musculature → impaired venous blood flow → consequent leg swelling and pain.
Rarely life threatening on its own but can cause PE.
Explain the aetiology of DVT.
3 factors (known as Virchow’s triad) , individually or together, lead to most DVTs :
- vessel injury,
- venous stasis,
- and activation of the clotting system (hypercoagulability)
What are the types of DVT and what does this mean for management?
Risk factors have a major impact on determining the length of time that anticoagulant therapy is offered.
In order of increasing risk of recurrent VTE:
- Major transient provoked (e.g. surgery lasting >60 minutes) within last 3 months
- Minor transient provoked (e.g. COCP, hospitalisation), within last 2 months
- Unprovoked
- Persistent provoked (e.g. active cancer)
List some risk factors for DVT.
- 3 or more days of bed rest
- Major surgery in last 3 months
- Hospitalisation in last 2 months,
- Trauma or fracture → immobilisation
- Previous VTE
- Active cancer
- Old age
- Pregnancy/postnatal
- Medical illness (esp infection, inflammation, immobility)
- Mutations/FH:
- Factor V Leiden (x3-4 risk),
- Prothrombin gene G20210A mutation
- Antithrombin deficiency
- Antiphospholipid antibody syndrome
- Drugs: COCP, tamoxifen.
- Flight >4hrs
- Smoking
- Obesity
Name a genetic condition which can predispose to clots.
Factor V Leiden
How does Factor V Leiden increase risk of DVT?
- Factor V is part of the coagulation cascade (see below)
- Mutation in the F5 gene causes factor V Leiden thrombophilia
- Usually the function of FV is inactivated with Activated Protein C (APC) to stop too much clotting but in Factor V Leiden this does not occur –> clotting happens for longer than usual –> abnormal blood clots
What percentage of people with Factor V Leiden thrombophilia ever develop abnormal clotting?
Only about 10 percent of individuals with the factor V Leiden mutation ever develop abnormal clots.
Apart from DVT, name another risk associated with Factor V Leiden thrombophilia.
- Miscarriage in the second/third trimester of pregnancy (x2-3 risk)
- Pulmonary emboli
What is the inheritance pattern of Factor V Leiden?
Factor V Leiden is an autosomal dominant genetic condition that exhibits incomplete penetrance i.e. not everyone will develop the disease.
What are the clinical features of DVT?
- Unilateral calf swelling - difference of >3cm between limbs measured 10cm below the tibial tuberosity
- Localised pain long deep venous system - palpate adductor canal and popliteal fossa
- Redness and warmth
- Coolness
- Prominent superficial veins - not varicose but dilated over foot and leg
Uncommon:
- swelling of entire leg
- plhegmasia cerulea dolens
Which 2 signs can be used to confirm DVT?
- Hofman’s sign - tenderness with dorsiflexion of the foot
- Pratt’s sign - calf pain on palpation
Both poor sensitivity and specificity.
What is phlegmasia cerulea dolens?
Cyanosed and painful leg due to ischaemia - massive DVT can obstruct not only the venous outflow but also the arterial
How do you diagnose DVT?
Calculate Wells score - assess pre-test probability
Ultrasound imaging - 1st line is venous duplex ultrasound if Wells’ score of 2 or more or <2 but with elevated D-dimer.
- Alternatively CT
Quantitative D-dimer level - where Wells’ score is <2. Breakdown product of cross-linked firbin so elevated in acute clots.
Other tests:
Bedside - pregnancy test,
Bloods- FBC (suggesting malignancy e.g. anaemia/leucopenia, high Plt), INR & aPTT (required before starting warfarin and IV heparin respectively) , urea & creatinine, LFTs (?cancer, hepatic dysfunction before starting anticoagulants) , thrombophilia screen
Imaging - whole leg US,
Describe how you would assess the Wells’ score.
Assesses clinical PROBABILITY of DVT and what should be done next.
What is the treatment of confirmed DVT?
Anticoagulation for at least 3 months (up to 6 months in active cancer).
Type depends on:
-
Renal impairment
- GFR 15-50ml/min → api/rivaroxaban OR VKA +/- heparin bridging
- GFR <15ml/min → LMWH/UFH OR VKA + heparin bridging
-
Active cancer
- DOAC unless unsuitable
-
Antiphospholipid syndrome
- VKA + heparin bridging
Conservative:
Physical activity - helps reduce port-thrombotic syndrome
Gradient stockings - for patients with acute/chronic symptoms of DVT
Surgical:
IVC filter - where there is active bleeding, or post-surgical cause
In a patient with renal impairment (for example), why do you need to give both heparin and warfarin as initial treatment for DVT?
Heparin works immediately providing anticoagulation to prevent the thrombus enlarging. Warfarin takes at least 48 hours to produce a therapeutic effect and therefore should be started at the same time as the heparin. When the INR is within the therapeutic range, the heparin can be discontinued.
Must maintain INR between 2.0 and 3.0
Maintain for 3-6months
NB: aspirin has no therapeutic effect in DVT.
Which patients might benefit from an IVC filter?
Those who cannot be given anticoagulant therapy (e.g. if they have had recent surgery or bleeding diathesis). It stops PE
What can be used to reverse the effects of UFH?
Protamine
What is the MOA of fondaparinux? Dalteparin?
Fondaparinux binds to its binding site on antithrombin (AT), resulting in irreversible conformational changes, which enables it to inhibit Xa, which is needed to activate factor II (prothrombin) to thrombin.
Dalteparin (and other LMWH) bind to factor X and AT promoting antithrombin’s activity in blocking key reactions in the clotting cascade
What is the MOA of warfarin?
Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the vitamin K which is needed for activating prothrombin.
Which anticoagulant should be used in pregnant women with DVTs?
LMWH (e.g. enoxaparin, dalteparin ) or subcutaneous UFH
Identify the possible complications of deep vein thrombosis (DVT) and its management
- PE - treated same as DVT
- bleeding during initial treatment - usually from previously unknown pathological lesion
- post-thrombotic syndrome - caused by chronic obstruction of venous outflow +/- destruction of venous valves –> venous hypertension. Usually within 2years of acute DVT episode and occurs in up to half of patients.
Low likelihood:
- heparin-induced thrombocytopenia (HIT)
- heparin resistance/aPTT confounding
- bleeding during long-term/extended treatment
- osteoporosis due to heparin treatment
Summarise the prognosis for patients with deep vein thrombosis (DVT)
- Depends on extent of DVT
- Whether it is provoked or idiopathic predicts recurrence risk
- Below-knee DVTs have a GOOD prognosis
- Proximal DVTs have a greater risk of embolisation
If a patient develops DVT whilst on oral contraceptive pill, should it be discontinued? If started on warfarin what should you tell her?
YES - must not be started in the future
If on Warfarin, she must not get pregnant because of its teratogenicity - different form of contraception required.
Why does thrombophilia predispose to DVT?
Natural anti-coagulants include protein C, protein S and anti- thrombin III amongst others.
The most common thrombophilic disorder is the presence of factor V Leiden. One in twenty of a Northern European population might be expected to be heterozygous for this finding.
There are also acquired thrombophilic disorders notably the antiphospholipid antibodies which predispose to arterial as well as venous thrombo-embolic problems.
What medication and dose is used in the prevention of DVT in a high risk patient initially?
Tinzaparin 4500 units sc OD - LMWH.
This is preferred over an unfractionated heparin (only used in certain cases e.g. renal failure)
What must you monitor on tinzaparin?
- platelets
- signs of bleeding and bruising
- liver and renal function
- potassium
What is the difference between DVT and VTE and superficial thrombophlebitis?
VTE - includes DVT and PE
Superficial thrombophlebitis - aka superficial vein thrombosis, affects veins superficial to the musculature ,
How common is DVT?
1 in 1000 incidence
⅔ present as DVT alone, ⅓ as PE
How common is DVT?
1 in 1000 incidence
⅔ present as DVT alone, ⅓ as PE
What are the side effects of heparin?
- Alopecia
- Thrombocytopenia (usually 5-10days after treatment)
- Hyperkalaemia - as it supresses aldosterone secretion
- Osteoporosis
- Priapism
What are the side effects of heparin?
- Alopecia
- Thrombocytopenia (usually 5-10days after treatment)
- Hyperkalaemia - as it supresses aldosterone secretion
- Osteoporosis
- Priapism
- Rashes around injection site
- Hypersensitivity
- Haemorrhage
Using the BNF, work out the treatment dose of enoxaparin for a 90kg man.
Enoxaparin: 1.5mg per kg ONCE daily for DVT treatment. 1.5 x 90 = 135mg.
This product comes as 120mg syringes and also comes in 20mg syringes, you could give the patient 140mg.
How long is the LMWH continued initially?
5 days or when INR in range - whichever is longer
LMWH is given as a bridging agent as warfarin is prothrombotic initially to protein C and S interference.
Which common comorbidity is not a risk factor for DVT?
Diabetes
What is the desired INR in an uncomplicated DVT?
NB that DOACs like Apixaban are still first line.
2.0-3.0
What is the algorithm for DVT management depending on Wells’ score?
<2 (15% risk) → D dimer +/- US
_>_2 (40% risk) → USS +/- discuss or treat
What is shown?
Phlegmasia cerulea dolens - swelling, significant pain, and cyanosis
Tx: do not wait for Ix, immediately start Tx and refer to vascular surgery.
What are 3 differentials for DVT?
Large or ruptured Baker’s cyst
Cellulitis
Musculoskeletal trauma or injury (calf bleeding or haematoma, ruptured Achilles’ tendon or ruptured plantaris)
What tests should be sent before starting interim therapeutic anticoagulation?
FBC
Renal and hepatic screen
PT
aPTT
D dimer is not always required
NB: interim anticoagulation is given if the USS cannot be done immediately, but it should always be done within 24hrs.
Do you need to investigate for PE in DVT?
Not unless the patient has symptoms
Which treatment option is best for DVT in someone <50kg or >120kg?
Treatment with monitoring of therapeutic levels
Compare the DVT vs PE Wells score.
What is apixaban and rivaroxaban are not suitable?
Offer apixaban or rivaroxaban. If these are unsuitable offer:
- LMWH for 5 days followed by dabigatran or edoxaban
- OR LMWH with VKA for at least 5 days or INR 2.0 in 2 consecutive readings.
