Deep vein thrombosis (DVT) management considers diagnosis and therapy of DVT as well as prevention and risks of recurrence on stopping therapy. DVTs are treated in order to prevent pulmonary embolism (PE) fatality, morbidity and long-term pulmonary hypertension. DVT may also cause changes to the leg—post-thrombotic syndrome.
Prevention of DVT
In post-knee replacement patients on no anticoagulation 15% will have a proximal DVT and this can be reduced to 5.6% with low-molecular-weight heparin (LMWH).1 Much work has been done in trying to reduce hospital-related deaths and morbidity from DVT especially after knee and hip replacement and GPs will be familiar now with some of the novel oral anticoagulants (NOACs) licensed for this.
The average day for DVT formation post-op is day seven and 80% are subclinical. NICE guidance2 suggests that all medical and surgical patients should be assessed for VTE risk on admission to hospital using a number of factors including immobility, length of GA if surgical, trauma and type of surgery. In addition, bleeding risk should be assessed and reassessed.
Although aspirin has antiplatelet action and so prevents some VTEs it is not considered as effective as other anticoagulants and so is not recommended. In 2010 NICE recommended LMWH mainly for thromboprophylaxis with unfractionated heparin (UH) recommended for renal failure patients. Fondaparinux sc was also licensed for thromboprophylaxis and is a F10 inhibitor. In addition mechanical prevention using anti-embolism stockings (thigh or knee length), foot impulse devices or intermittent pneumatic compression devices (thigh or knee length) are recommended.2
A Cochrane review in 20113 reviewed the results of three direct thrombin inhibitors, one of which is dabigatran, compared to using LMWH in hip replacements and either LMWH or warfarin after knee replacements. Patients were aged 18 to 93 years old and a mean age was 66 years old. They state that without anticoagulation 44–90% of knee and hip replacement patients would have a DVT and that there is a risk of DVT from surgery up to eight weeks post-op. Risk of DVT on therapy is about 5%, although trial figures do vary. They found that oral dabigatran was as effective as LMWH and warfarin in prevention of VTE but caused more bleeding, had higher mortality but there were no severe liver complications (a previous thrombin inhibitor has been withdrawn due to hepatotoxicity). Dabigatran4 offers improved patient convenience and does not need INR testing.
More recently other oral F10 inhibitor NOACs have been approved and used. Apixaban may have side-effects such as anaemia, haemorrhage, contusion and nausea.5 It is superior in current trial work to LMWH with similar bleeding risk. Apibaxan is a twice-daily dosing whilst rivaroxaban and dabigatran are once a day.
Fondaparinux loses advantage in being a sc drug. Rivaroxaban compared to LMWH appeared to be more efficient at preventing VTE but with a small increased risk of major bleeding.6 NICE has not differentiated the NOACs in terms of recommendation and all can be used post-op. In general it is therapy for 32–38 days for patients having hip replacement and 10–14 days for patients post knee replacement.
Patients should stop HRT four weeks pre-op. The risk of VTE can also be reduced by using regional blocks whenever possible and the patient’s specialist should advise whether pre-existing anticoagulant prescriptions need to be stopped prior to surgery. The risks of bleeding are increased if there is active bleeding, other anticoagulant therapy, lumbar puncture, epidural, spinal anaesthesia, acute haemorrhoagic stroke, platelet count below 75x109/L, blood pressure 230/120mmHg or higher, inherited bleeding disorders and liver impairment.
NICE suggests different thromboprophylaxis regimens depending on different types of surgery. Patients with a plaster of Paris are considered at risk of VTE and would be offered LMWH.
Although DVT is common in untreated surgical patients, especially hip and knee replacement patients, it is the unwell medical patients who account for 70–80% of PE deaths.2 40% of medical patients have a risk factor for VTE, many of them are elderly and immobile regardless of other medical conditions.
Routine screening of relatives of patients with an unprovoked DVT to diagnose thrombophilia is not recommended1 as evidence suggests that a number of these patients will be at low risk of DVT and the evidence for therapeutic intervention in this group is lacking. There may be families and situations however in which screening appears appropriate.
Although anticoagulation reduces risks of VTE it does not bring the risk to zero and the GP still needs to be cautious in assessing a patient with suspicious symptoms or signs even if they are on anticoagulant therapy.
Prevention of DVT recurrence
If a DVT has been provoked (ie. by a transient problem like surgery, trauma, HRT use) then the risk of recurrence can be reduced by removal of these risks. If the patient has an immovable problem like a thrombophilia then he or she will remain at risk of recurrence and their DVT is considered to be unprovoked.
NICE suggests that a DVT in a patient with active cancer is unprovoked because the risk is unchanging but GPs will be aware of changes in cancer and therapy status for their patient. Patients with unprovoked VTE should have anticoagulation for three months but it may need to be continued for longer. The bleeding risk (baseline risk of major bleeding of 1.77% per year) continues. Overall baseline risk of DVT recurrence in the first year is 8.4% and then 5.8% the next year.7 Duration of therapy needs to be individualised weighing up risks and advantages.
Thrombophilia testing is not recommended whilst the patient is on anticoagulation but risk stratification becomes important if considering stopping therapy and testing for antiphospholipid antibodies. Thrombophilia testing may then be sensible especially if there is also a first degree relative with an unprovoked DVT history.7 In order to test for antiphospholipid syndrome anticoagulation would need to be stopped for a short time.
In part one of this series we looked at deficiencies of natural anticoagulants. Protein C deficiency, more commonly increased activated protein C resistance, often resulting from Lieden gene mutation or deficiency of protein S are associated with an increased risk of thrombosis. Patients need to consent to testing as a positive test might be an indication for lifelong anticoagulation. Alternatively the information can be used with affected patients to provide anticoagulation during higher risk procedures eg. long haul flights. Patients with a provoked DVT eg. recent knee replacement would not be routinely screened for hereditary defects in coagulation.
Patients who present with a PE are more likely to have recurrent VTE.
Patients at high risk of DVT recurrence may be on rivaroxaban, warfarin or LMWH as a long-term prevention.
As many as 10% of PEs are rapidly fatal and a further 5% die later.8 PEs can cause secondary pulmonary hypertension and post-mortem of patients with presumed primary pulmonary hypertension has also suggested an incidence of asymptomatic PEs. Patients may have no symptoms or pleuritic chest pain, haemoptysis, breathlessness or collapse with hypotension or sudden death. Without anticoagulation post -joint replacement the rate of symptomatic or fatal PE is 0.5% and this can be reduced by anticoagulation by a factor of 3–5.9
Some 40–50% of patients with symptomatic DVT and no PE symptoms have positive ventilation-perfusion scans3 demonstrating asymptomatic embolism. It is impossible to be certain which DVT will produce PE of significance to the patient. The highest risk of death from post-op PE is days 3–7 but risk continues for up to three months. 20–30% of PE patients have no known predisposing factors.10
Diagnostic probability is considered using the two level Wells PE score in which high risk is a score of five or more points and includes signs, symptoms, risk factors and signs of DVT largely. Again this is available to download to computer and free phone apps.
If the score is high then the patient has lung scanning using ventilation/perfusion single photon emission computed tomography (V/P SPECT) or CT pulmonary angiogram (CTPA). If this is positive for a thrombus then anticoagulation is started, although it may be given whilst awaiting the scan if there is a delay. If the test is negative then any obvious DVT will need investigation. Patients with a clinically possible PE but a low probability Wells PE score have a d-dimer and if it is negative they are told they do not have a PE. If the d-dimer is positive they are triaged into a scan and may need anticoagulation whilst waiting.
Therapy for PE is with LMWH or fondaparinux. Patients with renal failure or going on to thrombolysis because they are haemodynamically unstable or with an increased risk of bleeding should be treated with UH.
If the patient has cancer and PE they are offered LMWH for six months. Other patients are stabilised on warfarin for three months and then an individualised decision made regarding stopping therapy depending on continuing risk factors, bleeding risk and patients’ views. Patients at low risk of bleeding but with an increased risk of recurrent PE may need to continue on warfarin long-term. In summary, anticoagulation after PE is for a minimum of three months and is usually for six months, but may be extended.
NOACs are not in the European guidelines for PE therapy at present as their guidance is dated 2008 but NICE has appraised the use of rivaroxaban and is currently appraising dabigatran in PE.
NICE recommends rivaroxaban for the treatment of acute PE at 15mg bd for the first 21 days followed by 20mg once daily thereafter.11 Like most NOACs the dose is reduced in renal impairment and was not given in the trial if the patient’s eGFR was below 30mls/min. NICE lists possible side-effects of rivaroxaban as anaemia, dizziness, headache, fainting, bleeding events, tachycardia, hypotension, stomach pain, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus, rash, bruising, pain in the extremities, fever, and swelling of ankles and feet.
In the trial data submitted to NICE 25% of patients had a DVT as well as their PE and the average age was 58 years. Similar rates (11%) of people stopped therapy in the warfarin and rivaroxaban arms of the trial and there were similar rates of bleeding and recurrent VTE. Rivaroxaban was more cost effective up to 12 months of trial data. There is no current trial to support its use above LMWH in cancer patients.
Some 5–10% of PE patients have a massive PE with shock and are haemodynamically unstable, their risk of early death is >15%. This group may benefit from thrombolysis using plasminogen activators like urokinase or rt-PA which although increase bleeding risk can reduce mortality.
Mechanical thrombectomy is also an option in patients with massive PE.
Between 2–4% of patients post PE will develop CTEPH (chronic thomboembolic pulmonary hypertension). This has become much easier to suspect with the finger oximeter in general practice. A patient with breathlessness of unknown cause and no particular signs but hypoxic in surgery raises a suspicion of pulmonary hypertension. This may be idiopathic or secondary to many causes, the most common in practice is COPD, but may also be due to PE. Patients require spirometry, CXR, ECG and echocardiogram to look for right heart strain and referral to OPC then onwards to regional centres for right sided heart catheterisation and pulmonary artery wedge pressure readings. Treatment is endarterectomy of thrombus if possible or pulmonary vasodilators.
Patients with PE are traditionally treated as inpatients (IP). A study from the Netherlands triaged patients attending hospital between 2008–2010 with PE for outpatient (OPC) LMWH and warfarin therapy rather than IP care. Patients needed to be stable and have good social home support. About 50% of patients with PE were suitable for OPC therapy. 26% of patients were over 65 years old, 9% had active cancer and two patients died of their cancer during the three month follow up. Patients were allowed home within 24 hours of admission. Of the 297 suitable patients, five had recurrent non-fatal PE (1.7%) and one had a DVT (0.3%). One patient had a fatal intracranial bleed on day seven and one anaemia due to an abdominal muscle haematoma (0.7%).12 15 patients (5.1%) had non-major bleeding of which five had large skin haematomas, six had visible haematuria, three had haemoptysis and one had an ovarian bleed. OPC PE therapy therefore looks a future possibility.
There is little about pulmonary vein thrombosis in the literature but presumably patients, particularly with lung diseases, may incur DVTs of the pulmonary circulation. Present therapy for patients with VTE involves the thrombin inhibitors, F10 inhibitors and warfarin. The use of thrombolysis for large VTE has become standard but there is not yet the intensive use of multiple anticoagulants, as in PCI for STEMIs, to prevent thrombus propagation. The use of oral anticoagulants without dosage monitoring is a huge step for patient care in terms of convenience, maintaining usual lifestyle, cost and provision of therapy to patients needing monitored dosing systems like venalinks.
The sixth article in this series reviews anticoagulants and fibrinolytic use in cerebrovascular accident, transient ischaemic attacks and atrial fibrillation.
Conflict of interest: none declared
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