Core Topics in General & Emergency Surgery: Companion to Specialist Surgical Practice (70 page)
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Authors: Simon Paterson-Brown MBBS MPhil MS FRCS
Guidelines
Over the last few years there has been a proliferation of guidelines for the prevention of VTE, with national guidelines developed in Scotland (SIGN 122)
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and England and Wales (NICE CG92).
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All hospitals should formally adopt and implement guidelines for VTE prevention and audit their practice.
Studies investigating strategies for the prevention of VTE have used angiography or more recently ultrasonography to confirm the presence of a thrombotic event, with the majority of these being subclinical below-knee DVTs. There is a strong association between asymptomatic DVT and the development of symptomatic VTE (proximal DVT or PE)
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and it is therefore essential to introduce thromboprophylaxis strategies in patients at risk in order to reduce the morbidity and mortality associated with this disease. While it is possible to identify groups at high risk of VTE,
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it is not possible to identify the specific patient who will develop a symptomatic thrombosis, nor the individual who will develop a sudden massive PE. In 70–80% of patients dying of a PE in hospital, a diagnosis of VTE was not considered prior to autopsy, and most patients with PE have had no previous symptoms suggestive of DVT.
The prevalence of postoperative PE is now considerably lower than it was some years ago due to the use of improved surgical and anaesthetic techniques, early mobilisation of patients and the systematic introduction of chemical thromboprophylaxis.
Mobilisation and leg exercises:
While evidence to support early mobilisation and leg exercises in reducing the risk of VTE is scarce, immobility significantly increases the risk of VTE, and trials of bed rest for medical illnesses demonstrated no evidence of benefit.
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Mobilisation and leg exercises are simple interventions and should be encouraged where appropriate to reduce thrombosis risk.
Mechanical thromboprophylaxis:
Mechanical methods of prophylaxis include graduated elastic compression stockings (GECSs), intermittent pneumatic compression (IPC) devices and venous foot-pumps. These methods are designed to reduce venous stasis and improve venous flow in the leg veins.
GECSs have a compression profile of 18 mmHg at the ankle, 14–15 mmHg mid-calf and 8 mmHg at the knee. They are simple, safe when applied correctly (care should be taken not to use them in patients with severe peripheral vascular disease) and moderately efficacious in preventing VTE without any increased risk of bleeding.
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Graduated compression stockings produce a highly significant risk reduction in postoperative venous thomboembolic disease of 68% in moderate-risk patients.
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A recent Cochrane review confirmed the effectiveness of GECSs in reducing the risk of venous thromboembolic disease, particularly when used on a background of other methods of prophylaxis.
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All surgical patients at risk of VTE should have GECSs applied unless contraindicated.
There are a number of different manufacturers of IPC devices, which supply intermittent low pressure (typically 40 mmHg) for 1 minute with a 90-second period of decompression. This increases the velocity of venous return and blood flow and may also enhance fibrinolysis
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and inhibition of the tissue factor pathway.
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A meta-analysis
47
of the use of mechanical methods for thromboprophylaxis reported DVT rates of 9.9%and 17.6% for IPC versus 20.3% and 27% for placebo. Adherence with IPC is frequently less than optimal in ‘real-life’ settings.
A major limitation in the studies of intermittent pneumatic compression (IPC) devices is the relatively small numbers of patients included. When used alone in patients undergoing high-risk surgery they appear to lack efficacy, and further assessment of their role is required.
Vitamin K antagonists:
It has been known since 1959 that warfarin anticoagulation significantly reduces the incidence of thromboembolic disease when used for prophylaxis.
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However, this method is not routinely used, mainly because of the considerable risk of haemorrhage, either spontaneous or related to the surgery.
Aspirin and antiplatelet agents:
The Medical Research Council sponsored a double-blind, placebo-controlled study of 303 surgical patients, which showed no reduction in postoperative DVT with 600 mg aspirin taken immediately before and for 5 days after surgery.
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A meta-analysis of thromboprophylaxis following total hip replacement, including data from 56 randomised trials, showed no benefit for aspirin in preventing DVT.
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However, in the meta-analysis of the Antiplatelets Trialists' Collaboration,
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aspirin was found to significantly reduce DVT, although the poor quality of some of the studies included has led to many doubts regarding this finding. Aspirin may have a role in prophylaxis of low-risk groups.
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Heparins:
The use of low-dose unfractionated heparin (UFH) for thromboprophylaxis has now largely been superseded by low-molecular-weight heparin (LWMH) due to the latter's superior bioavailability, once-daily dosage and the reduced incidence of HIT. Heparins are renally excreted and therefore UFH may be preferred in patients in whom there is an increased risk of accumulation (those with significant renal impairment).
A meta-analysis of UFH prophylaxis in surgery showed a reduction in DVT and PE by two-thirds when compared to placebo, with a 2% increase in minor bleeding events.
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Studies have consistently shown reductions in DVT and PE by two-thirds with both UFH and LMWH, with a slightly reduced risk of bleeding with LMWH compared with UFH. Two meta-analyses have shown superior results with LMWH after total hip replacement with regard to postoperative DVT (risk reduction of 17–32%) and PE (risk reduction of 50%).
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Higher doses of LMWH should be given to high-risk general surgical patients as these provide greater protection than lower doses. In cancer patients undergoing surgery, prophylaxis with dalteparin 5000 units daily was shown to be significantly more effective than 2500 units daily, without an increased risk of bleeding.
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Compared with no prophylaxis, LMWH reduces the risk of clinical PE and clinical VTE by approximately 70%, and is associated with a possible reduction in the risk of death from any cause. However, LMWH also leads to an approximately doubling of the risk of wound haematoma and is associated with a small increase in major bleeding, which is higher in those with renal failure.
Fondaparinux:
Fondaparinux is a synthetic pentasaccharide and a potent, highly selective, inhibitor of factor Xa. It has a longer half-life, is associated with a slightly increased risk of bleeding and is more expensivethan LMWH. For these reasons, fondaparinux is less commonly used for VTE prevention in general surgical patients. As LMWH is of porcine origin, fondaparinux can be used as an alternative in patients with religious objection to the use of porcine products.
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New oral anticoagulants:
Dabigatran etexilate, an oral direct thrombin inhibitor, and rivaroxaban and apixaban (oral anti-Xa anticoagulants) have been licensed for thromboprophylaxis following hip and knee replacement surgery, but as yet there are few data for their use in general surgery.
Patients remain at increased risk of VTE once discharged after a surgical procedure, with a peak at 3 weeks postoperatively. Clinical trials of extended prophylaxis (4 weeks of LMWH vs. 1 week LMWH) after general surgery showed a significant reduction in venographically detected thromboses in those with cancer.
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One randomised trial of 300 patients undergoing abdominal or pelvic surgery receiving either 9 or 30 days of LMWH showed two proximal DVTs in those receiving short-term treatment, compared to one in those in the extended group.
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There are now many guidelines that provide recommendations on how to reduce the risk of VTE in surgical patients (and in other patient groups). In the UK these include the National Institute of Health and Clinical Excellence (NICE) Clinical Guideline 92 (Venous thromboembolism: reducing the risk
29
) and the Scottish SIGN 122 (Prevention and management of venous thromboembolism
30
). What these guidelines have in common is the recommendation that all patients should be assessed for their risk of developing a venous thrombosis based on both their individual predisposing factors and the risk associated with their illness and/or proposed surgical procedure. Patients assessed as being at high risk of VTE should be given thromboprophylaxis, which should be continued after discharge in specific high-risk groups.
Many patients present with leg pain or swelling, chest pain or breathlessness, and it is not possible to exclude VTE on the basis of clinical history and examination alone. Approximately 25% of patients with symptoms thought to be due to a DVT or PE will have those diagnoses subsequently confirmed; therefore, many could be unnecessarily exposed to imaging investigations with their associated risks. As a result, over the last 5–10 years, diagnostic strategies have been developed that utilise both clinical pretest probability scoring tools (for DVT and PE) and D-dimer estimation to reduce the requirement for imaging investigations.
Clinical features of DVT
The symptoms and signs of DVT tend to be non-specific. Most often patients complain of pain, swelling and redness of the lower limb, and on examination mild erythema, tenderness along the thigh or calf, muscle induration and mild pyrexia are found. However, many patients with DVT will have none of these clinical features. Unilateral pitting oedema is the most significant clinical sign, indicating thrombosis in 70% of patients. Homan's sign (pain or discomfort on foot dorsiflexion) is unreliable.
Patients with distal iliac or femoral vein thromboses can present with a very painful, swollen, white leg (phlegmasia caerulea alba). A rare but dramatic presentation is that of ‘phlegmasia caerulea dolens’, which occurs when the whole iliac system is thrombosed. The entire leg is swollen, acutely painful, dusky blue in colour and patchy areas of venous gangrene can develop. The cyanosis and swelling distinguish this from arterial ischaemia (in which the limb is white and rarely is there any swelling).
Venous thrombosis is not the only cause of a painful and/or swollen leg. Rupture of a Baker's cyst presents with sudden-onset lower leg pain, swelling and cellulitis, with a painful and erythematous lower limb. Muscular tears and bleeding into a muscle in a patient already on anticoagulant therapy can also be difficult to differentiate from a DVT. It is also important to remember that (rarely) malignancies such as sarcoma can present with a unilateral swollen leg.
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Clinical prediction tools incorporate clinical symptoms, signs and risk factors of thrombosis, and assess the likelihood of a patient having a DVT. The most frequently used clinical prediction tool for DVT is the Wells score,
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which has been adapted to categorise patients as ‘DVT likely’ or ‘DVT unlikely’
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(
Table 14.1
). The Wells score is not validated for use in patients with previous DVT or in hospitalised or pregnant patients; initial investigation in such patients should be by appropriate imaging.
Table 14.1
Clinical model predicting the pretest probability of DVT
*
| Clinical characteristic | Score |
| Active cancer (patient receiving treatment for cancer within previous 6 months or palliative) | 1 |
| Paralysis, paresis or recent plaster immobilisation of the lower extremities | 1 |
| Recently bedridden for 3 days or more, or major surgery within 12 weeks | 1 |
| Localised tenderness along the distribution of the deep venous system | 1 |
| Entire leg swollen | 1 |
| Calf swelling at least 3 cm larger than that on asymptomatic leg (10 cm below tibial tuberosity) | 1 |
| Pitting oedema confined to symptomatic leg | 1 |
| Collateral superficial veins (non-varicose) | 1 |
| Previously documented DVT | 1 |
| Alternative diagnosis at least as likely as DVT | − 2 |
*
A score of 2 or higher indicates that the probability of DVT is likely; a score of less than 2 indicates that the probability of DVT is unlikely.
Reproduced from Wells PS, Anderson DR, Rodger M et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349(13): 1227–35. Massachusetts Medical Society. All rights reserved.
D-dimers are the product of fibrinolysis of cross-linked fibrin, and are usually (but not always) increased in patients with active VTE (i.e. active thrombus formation). There are a number of different D-dimer assays (qualitative and quantitative) available, many of which have been evaluated to determine clinically meaningful cut-off values for the exclusion of VTE.
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A systematic review of patient cohorts presenting with suspected VTE who were prospectively assessed using a clinical prediction tool and D-dimer testing found a rate of VTE of 0.45% (95% confidence interval 0.22–0.83) in those who were at low risk of VTE and had D-dimers below the cut-off value.
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Patients who are considered using clinical prediction tools to be ‘DVT unlikely’, without increased D-dimers, can be considered to have had a DVT excluded and do not require further investigation. It must be borne in mind, however, that D-dimers tend to be increased with increasing age, and in those with malignancy, recent surgery or acute infection. The clinical utility of requesting a D-dimer assay in these patient groups is therefore limited, and most patients within these groups are likely to need imaging to exclude a thrombosis. D-dimer levels are reduced in patients on anticoagulant drugs.
Venous ultrasound
Venous ultrasound is the investigation of choice for suspected DVT, with high sensitivity (94–99%) and specificity (89–96%) for the diagnosis of symptomatic lower-limb proximal DVT when compared to contrast venography. Sensitivity and specificity are considerably less for calf DVT.
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The outcome of patients with a negative initial scan appears similar to control populations; however, there is evidence that distal DVT may extend proximally and subsequently embolise.
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For that reason, many centres repeat the ultrasound in 1 week if the initial scan is negative.
Care should be taken in the interpretation of ultrasound scans when requested in individuals with a history of previous DVT. A scan report of echogenic or non-occlusive thrombus at the site of a previous clot could be due to chronic or ‘old’ DVT rather than a new event. Serial ultrasound (or venography) may be useful in such circumstances.
IP was extensively studied in the 1970s and 1980s and is currently still used to exclude DVT in a number of centres. A tourniquet is applied to the affected limb and changes in the volume of the limb measured after tourniquet removal. The sensitivity and specificity of IP for DVT (83% and 92%, respectively) are lower than with ultrasound, hence the preference for ultrasound for the diagnosis of DVT by many hospitals.
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Venography was for a long time the ‘gold standard’ for a diagnosis of DVT; however, it is painful, involves the use of contrast medium and radiation, and is rarely used today. Venography has now been superseded by duplex ultrasound imaging.
CT has a 95% sensitivity for DVT (proximal and distal) and 97% specificity.
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While it may not be routinely used for the diagnosis of peripheral venous occlusion, it is useful in the investigation of suspected proximal venous thrombosis (inferior and superior vena cava).
MRI and MRA can detect both peripheral and central venous thromboses, and are being studied for their role in the investigation of venous thrombosis. MRA is non-invasive, uses venous blood flow as the source of image contrast, but is not yet widely available. As with the other imaging modalities, MRA is sensitive and specific for proximal thrombosis, but has a lower sensitivity for distal thrombi. MRI is particularly useful for the investigation of suspected iliac thrombosis in pregnant women.
Ultrasonography by an experienced operator is now the investigation of choice for DVT. D-dimer testing has now been widely incorporated into diagnostic algorithms, allowing the exclusion of DVT in patients at low risk with D-dimers below the cut-off for that assay. Serial ultrasound scanning should be performed in those at high risk of DVT with an initial ‘negative’ ultrasound but D-dimers above the cut-off. More invasive investigations (e.g. CT, MRA, venography) should be reserved for those in whom there is thought to be iliac thrombosis not visualised by ultrasound, or if there is lack of concordance between clinical probability and the ultrasound scan result. Most centres will prefer to use CT or MRA rather than venography for the investigation of patients suspected of having an iliac thrombosis.
Clinical presentation and pretest probability
The symptoms and signs most commonly associated with a confirmed diagnosis of PE are (in order of descending frequency): dyspnoea, tachypnoea, pleuritic pain, apprehension, tachycardia, cough, haemoptysis, leg pain and clinical DVT. Clinical history and examination are insufficient to exclude a diagnosis of PE.
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As with DVT, the diagnostic process has been improved considerably by the introduction of clinical decision rules (such as the Wells (
Table 14.2
) and Geneva scoring systems), which risk stratify patients with suspected PE, and are used in combination with D-dimer testing. Using the PE Wells score and a quantitative D-dimer test to rule out PE, in those at low risk of PE with low D-dimers, 0–1.9 cases of PE would be missed/1000 patients screened.
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In practice, therefore, in patients at ‘low risk’ of PE with low D-dimers, a diagnosis of PE can be excluded. These clinical decision rules have not been validated in patients already hospitalised, nor in pregnant women. Hospitalised patients should therefore be investigated by appropriate imaging studies.
Table 14.2
Variables used to determine patient pretest probability for pulmonary embolism
*
| Clinical variable | Score |
| Clinical signs and symptoms of DVT (minimum of leg swelling and pain with palpation of deep veins) | 3 |
| PE as or more likely than an alternative diagnosis | 3 |
| Heart rate > 100 | 1.5 |
| Immobilisation or surgery in the previous 4 weeks | 1.5 |
| Previous DVT/PE | 1.5 |
| Haemoptysis | 1 |
| Malignancy (on treatment, treated in the last 6 months or palliative) | 1 |
*
Score > 4, probability of PE is ‘likely’; 4, probability for PE is ‘unlikely’. Alternatively, < 2 is low probability, 2–6 moderate and > 6 high.
Adapted from Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb Haemost 2007; 5(Suppl 1):41–50. With permission from John Wiley and Sons.
Chest X-ray (CXR)
Radiographic findings in PE are usually non-specific on a CXR; however, it will exclude other diagnoses (such as infection or pulmonary oedema).
CTPA is now the gold standard for detecting PE, with multislice scanners reporting sensitivities of 83–100% and specificity of 89–97%. These multislice CTPA scanners allow the entire pulmonary arterial tree to be visualised in less than 10 seconds, and in addition to demonstrating the presence or absence of a PE, an alternative cause for the patient's symptoms may be detected (not possible with V/Q scanning – see below). CTPA also gives an assessment of the right ventricular:left ventricular size, an indicator of the severity of the PE in the acute situation. A good-quality negative CTPA on a multidetector scan effectively excludes PE, and anticoagulation can safely be withheld in such patients.
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Until recently, V/Q scanning was the imaging investigation of choice for those suspected of having had a PE, but has been largely superseded by CTPA. It is relatively easily performed, is less invasive and cheaper than pulmonary angiography, and can be used as an alternative in patients with contraindications to CTPA. It is of most use in those with normal CXR without underlying lung disease.
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A normal V/Q scan excludes the diagnosis of PE (1% VTE in follow-up).
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Echocardiography can be particularly useful in unstable patients for whom transport to the radiology department is unfeasible. Right ventricular freewall hypokinesis and increased pulmonary pressures are highly suggestive of PE and can be considered diagnostic if ultrasound evidence of DVT is also seen. It may also allow differentiation between other clinical conditions that can present in a similar fashion, such as aortic dissection, myocardial infarction or pericardial tamponade.
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Currently, the clinical utility of MRI in the diagnosis of PE is low when compared with CTPA. Although preliminary studies suggest contrast-enhanced magnetic resonance angiography (ce-MRA) has a similar sensitivity and specificity to other imaging techniques,
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there is less access to patients (who may be clinically unstable) whilst in the magnet, the duration of scanning is longer and MRI scanning is generally less easily available. However, MRI scanning has some advantages: firstly, it does not require ionising radiation, which is beneficial for women of childbearing age and/or those who are pregnant; secondly, MRI contrast agents are considered to have fewer side-effects than the iodinated media required for CT; and thirdly, it is possible to carry out a comprehensive protocol of magnetic resonance venography and pulmonary angiography (taking less than 20 minutes in total). As a result, consideration could be given to using MRI in patients with contraindications to contrast media, young women with a low clinical probability of PE, and in pregnancy. However, the other imaging modalities discussed above remain the mainstay of investigation at the present time.
Clinical assessment of DVT and PE is especially unreliable in pregnancy and the minority of pregnant women undergoing objective investigation for VTE will have that diagnosis confirmed. It is important, therefore, that the risks of imaging (both to the mother and the foetus) are minimised. The Royal College of Obstetricians advises that pregnant women suspected of having a PE have a duplex ultrasound performed,
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with V/Q scanning or CTPA reserved for those with negative ultrasound scans.
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CTPA has the disadvantage of a high radiation dose to the woman's breasts and an increased lifetime risk of developing breast cancer, with V/Q resulting in a considerably lower radiation dose to the mother.
