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Prevention of deep vein thrombosis and pulmonary embolus
PERIOPERATIVE CARE
Prevention of deep vein thrombosis and pulmonary embolus
Learning objectives After reading this article, you should: C
Tom Martin
C
Caroline Oliver C
be aware of the prevalence of venous thromboembolism in the perioperative period and its attendant complications be able to stratify patients according to their risk of perioperative venous thromboembolism understand the mechanism by which methods of prevention operate and the evidence for their use.
Abstract Venous thromboembolism is common in the perioperative period. Difficulties with diagnosis and the risks of treatment make prevention a clinical imperative. Preoperative risk assessment and appropriate prophylaxis is important to minimize morbidity and mortality. A range of mechanical and pharmacological interventions have been shown to significantly reduce the risk. A number of anaesthetic interventions are also recommended. Newer oral anticoagulants have been recommended for use after specific high-risk procedures.
Aetiology Factors promoting the formation and propagation of thrombus in the vascular system may be broadly divided into three groups known as Virchow’s Triad (Figure 1). The major risk factors for VTE are:
C
Keywords anticoagulation; deep vein thrombosis; pulmonary embolus; thromboprophylaxis; venous thromboembolism
C
C C C
Thrombus formation in the deep veins of the dependent extremities carries significant morbidity. Treatment of deep vein thrombosis (DVT) exposes patients to further risk and represents a considerable burden on healthcare resources. Migration of clot fragments can result in pulmonary embolism (PE) which may be fatal. These conditions, collectively termed venous thromboembolism (VTE), can be difficult to diagnose accurately. Thus prevention of this condition is a clinical imperative and one that has been the subject of recent UK Guidance.1
C C
C C C
C
C
C
C C C C
C C
Personal or family history of VTE Oestrogen-containing oral contraception or hormone replacement therapy in last four weeks Varicose veins with associated phlebitis Central venous catheterization Severe infection Dehydration Inherited or acquired thrombophilia Nephrotic syndrome Paraproteinaemia
Diagnosis
Incidence
Clinical diagnosis of DVT is unreliable as a variety of other conditions may be clinically indistinguishable (e.g. cellulitis, superficial thrombophlebitis or chronic venous insufficiency). More often the condition is unrecognized due to a lack of overt manifestations. The assay for D dimer (a fibrin degradation product) has a very low positive predictive value in the postoperative population. The use of a risk-scoring tool based on clinical findings and a D dimer assay may be useful to guide initial management. Contrast venography may be used to definitively diagnose a DVT, but this test is invasive and carries a risk of venous thrombosis. Duplex ultrasonography is a commonly used non-invasive method of diagnosis but carries significant resource implications. Computerized tomography (CT) and magnetic resonance imaging (MRI) are both sensitive and specific but their use is precluded in the clinical setting by cost. Pulmonary embolism may be equally difficult to diagnose due to the low specificity of clinical examination, electrocardiography, chest radiography and ventilation:perfusion scanning.
VTE accounts for 25,000 deaths annually in England. Many DVTs are clinically silent and the published incidence is likely to be a significant underestimate. Routine ultrasonography of patients after major surgical procedures reveals that, without prophylaxis, the incidence of DVT is 29%. The risk is particularly high after orthopaedic surgery with an estimated 40% developing DVT and 5% suffering PE. In the absence of malignancy, the lowest risk of VTE is after gynaecological, head and neck and laparoscopic abdominal surgery.
Tom Martin MBBS BSc(Hons) FRCA is a Specialty Registrar at the Bristol School of Anaesthesia, UK. Conflicts of interest: none declared. Caroline Oliver FRCA is a Consultant in Anaesthesia and Critical Care at Frenchay Hospital, Bristol, UK. Her special interest is neuroanaesthesia and critical care. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
Malignancy or cancer treatment Obesity (body mass index 30 kg/m2) Pregnancy and puerperium Acute medical illness Recent myocardial infarction or stroke Major surgery Trauma (major or lower extremity) Immobility Increasing age Inflammatory bowel disease
580
Ó 2009 Elsevier Ltd. All rights reserved.
PERIOPERATIVE CARE
Mechanical
Virchow’s Triad
Graduated compression stockings (GCS) are specifically profiled to exert decreasing circumferential pressure on the leg towards the pelvis, thus creating a pressure gradient favouring venous return from the foot (the Sigel profile). They may be used throughout the perioperative period although should not be used for patients with severe peripheral vascular disease (ankle:brachial pressure index <0.8), peripheral neuropathy or gross limb oedema. As a sole intervention the use of GCS reduces the risk of DVT by 51%. If used in combination with a pharmacological method, the risk is reduced by 56% compared to pharmacological methods alone. Intermittent pneumatic compression (IPC) of the lower leg works on a similar principle by the sequential inflation of bladders within a cuff applied around the calf. As well as reducing venous stasis these devices are thought to stimulate fibrinolytic activity. As a sole intervention they are no more effective than GCS, but, when combined with another non-mechanical method of prophylaxis, they have been shown to reduce the incidence of PE by 50%. Foot impulse devices are an alternative for cases where GCS or IPC are unsuitable. These apply a short and rapid impulse of pressure to the foot. This compresses the venous plexus of the sole displacing blood into the deep veins of the leg and mimicking the effect of weight bearing. These devices may be slightly more effective than GCS or IPC in reducing the risk of DVT. A combination of mechanical methods may confer some additional protection against DVT. Although these techniques are an important part of preventing VTE, it must not be forgotten that the mainstay of mechanical prophylaxis is enabling and encouraging early mobilization after surgery.
Hypocoagulability • Major sugery/trauma • Pregnancy • Osetrogen therapy • Malignancy • Inherited thrombophilia
Venous thromboembolism
Change in blood flow • Immobility • Obesity • Pregnancy
Altered vessel wall • Trauma • Thrombophlebitis • Cellulitis
Figure 1
Definitive diagnosis rests on demonstration of a filling defect during CT pulmonary angiography.
Prevention of VTE Pharmacological
No single technique can completely abolish VTE as a complication of surgery. Instead, a range of mechanical and pharmacological interventions may be used, based on preoperative risk stratification (Table 1).
Heparin Unfractionated heparin (UFH) inhibits coagulation by indirectly inhibiting thrombin via a number of mechanisms. Low molecular
Guidelines from the American College of Chest Physicians for prevention of VTE (2008)2 Level of risk Low risk - Minor surgery in mobile patients - Medical patients who are fully mobile Moderate risk - Most general, open gynaecological or urological procedures - Medical patients, bed rest or sick - Moderate VTE risk plus high bleeding risk High risk - Hip or knee arthroplasty, HFS, major trauma, SCI
DVT risk without thromboprophylaxis (%)
Suggested thromboprophylaxis options
<10
No specific thromboprophylaxis. Early and ‘aggressive’ ambulation
10e40
LMWH or fondaparinux
Mechanical thromboprophylaxis 40e80
LMWH, fondaparinux or oral vitamin K antagonist (INR 2e3) plus mechanical thromboprophylaxis Mechanical thromboprophylaxis
- High VTE risk plus high bleeding risk
LMWH, low molecular weight heparin; INR, International Normalized Ratio; HFS, hip fracture surgery; SCI, spinal cord injury.
Modified, with permission, from Geerts WH et al.2 Table 1
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
581
Ó 2009 Elsevier Ltd. All rights reserved.
PERIOPERATIVE CARE
Hip- and knee- replacement surgery
weight heparin (LMWH) acts predominantly by the inhibition of Factor Xa which catalyses conversion of prothrombin to thrombin. In contrast to UFH, prophylaxis with LMWH is more effective at preventing VTE and may be given once daily. In addition, there is reduced incidence of heparin-induced thrombocytopoenia (HIT) and a lower incidence of bleeding. As a result, LMWH has become the mainstay of pharmacological thromboprophylaxis and should be considered for all but the most straightforward procedures. The use of LMWH combined with a mechanical intervention reduces risk of DVT by 71%.
This constitutes the greatest risk of perioperative VTE after elective surgery. Accordingly, these patients benefit from thromboprophylaxis that extends beyond hospital discharge. The logistical difficulties of managing LMWH administration outside hospital have been recently overcome by the development of a number of directly acting oral anticoagulants. Dabigatran and rivaroxaban Dabigatran is an oral direct thrombin inhibitor. Rivaroxaban is a direct Factor Xa inhibitor. Each has been recently recommended for the primary prevention of VTE following total hip- or kneereplacement surgery.3,4 Treatment should continue for two weeks following knee replacement and five weeks following hip replacement. Each are at least as effective as LMWH in preventing VTE but may be associated with greater risk of significant bleeding.
Aspirin Aspirin inhibits platelet function by irreversible inhibition of cyclooxygenase-1 (COX-1). Although it has some efficacy in reducing the risk of VTE in surgical patients, it is less effective than LMWH and may be associated with more bleeding events. There appears to be no additional benefit in combining aspirin with LMWH.
Anaesthesia and VTE
Warfarin Adjusted-dose warfarin therapy reduces the risk of DVT and PE and its efficacy is comparable to aspirin. However, it requires careful dosing and regular monitoring in addition to significantly increasing risk of major bleeding. As such it is not practical for routine prevention of VTE in the perioperative population.
A number of anaesthetic interventions may reduce the risk of perioperative VTE. When positioning patients for surgery, useful measures include the use of heel pads to avoid calf vein compression and the elevation of limbs to promote venous return. IPC devices are ideally suited for use during general anaesthesia. Avoidance of dehydration reduces the risk of hypercoagulability. The sole use of neuraxial blockade has been associated with a reduction in post-operative VTE after hip surgery. This benefit appears to be lost when a combined technique is used. It is suggested that other regional techniques may carry similar advantages. However, it is important to consider the timing of anticoagulation in relation to any regional technique, in particular, neuraxial blockade. A
Dextrans Dextrans inhibit red cell and platelet adhesion as well as potentiating antithrombin. Preparations of large molecular weight dextrans (e.g. dextran 60 or 70) are poorly excreted and may exert an antithrombotic action that lasts for several days. They are administered as a colloid and must be given in volumes exceeding 1.5 l in order to achieve an anticoagulant effect. Their use may be complicated by allergic reactions in up to 4% of patients and their efficacy of VTE prevention is comparable to aspirin. For these reasons they are rarely used for this indication alone.
REFERENCES 1 NICE Clinical guideline 46. Reducing the risk of venous thromboembolism in inpatients undergoing surgery. National Institute of Clinical Excellence; April 2007. 2 Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism; American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 381Se453. 3 NICE technology appraisal guidance 157. Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. National Institute of Clinical Excellence; September 2008. 4 NICE technology appraisal guidance 170. Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. National Institute of Clinical Excellence; April 2009.
Fondaparinux Fondaparinux is an antithrombin activator and thereby selectively inhibits Factor Xa. It exerts a similar anticoagulant effect to heparin but without the risk of HIT, making it an alternative for patients unable to take LMWH. Danaparoid and lepirudin Danaparoid inhibits Factors Xa and IIa and has an anticoagulant action similar to LMWH. Lepirudin is a direct thrombin inhibitor. Both are licensed for prevention of VTE in patients with HIT.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
582
Ó 2009 Elsevier Ltd. All rights reserved.
Prevention of deep vein thrombosis and pulmonary embolus
Learning objectives After reading this article, you should: C
Tom Martin
C
Caroline Oliver C
be aware of the prevalence of venous thromboembolism in the perioperative period and its attendant complications be able to stratify patients according to their risk of perioperative venous thromboembolism understand the mechanism by which methods of prevention operate and the evidence for their use.
Abstract Venous thromboembolism is common in the perioperative period. Difficulties with diagnosis and the risks of treatment make prevention a clinical imperative. Preoperative risk assessment and appropriate prophylaxis is important to minimize morbidity and mortality. A range of mechanical and pharmacological interventions have been shown to significantly reduce the risk. A number of anaesthetic interventions are also recommended. Newer oral anticoagulants have been recommended for use after specific high-risk procedures.
Aetiology Factors promoting the formation and propagation of thrombus in the vascular system may be broadly divided into three groups known as Virchow’s Triad (Figure 1). The major risk factors for VTE are:
C
Keywords anticoagulation; deep vein thrombosis; pulmonary embolus; thromboprophylaxis; venous thromboembolism
C
C C C
Thrombus formation in the deep veins of the dependent extremities carries significant morbidity. Treatment of deep vein thrombosis (DVT) exposes patients to further risk and represents a considerable burden on healthcare resources. Migration of clot fragments can result in pulmonary embolism (PE) which may be fatal. These conditions, collectively termed venous thromboembolism (VTE), can be difficult to diagnose accurately. Thus prevention of this condition is a clinical imperative and one that has been the subject of recent UK Guidance.1
C C
C C C
C
C
C
C C C C
C C
Personal or family history of VTE Oestrogen-containing oral contraception or hormone replacement therapy in last four weeks Varicose veins with associated phlebitis Central venous catheterization Severe infection Dehydration Inherited or acquired thrombophilia Nephrotic syndrome Paraproteinaemia
Diagnosis
Incidence
Clinical diagnosis of DVT is unreliable as a variety of other conditions may be clinically indistinguishable (e.g. cellulitis, superficial thrombophlebitis or chronic venous insufficiency). More often the condition is unrecognized due to a lack of overt manifestations. The assay for D dimer (a fibrin degradation product) has a very low positive predictive value in the postoperative population. The use of a risk-scoring tool based on clinical findings and a D dimer assay may be useful to guide initial management. Contrast venography may be used to definitively diagnose a DVT, but this test is invasive and carries a risk of venous thrombosis. Duplex ultrasonography is a commonly used non-invasive method of diagnosis but carries significant resource implications. Computerized tomography (CT) and magnetic resonance imaging (MRI) are both sensitive and specific but their use is precluded in the clinical setting by cost. Pulmonary embolism may be equally difficult to diagnose due to the low specificity of clinical examination, electrocardiography, chest radiography and ventilation:perfusion scanning.
VTE accounts for 25,000 deaths annually in England. Many DVTs are clinically silent and the published incidence is likely to be a significant underestimate. Routine ultrasonography of patients after major surgical procedures reveals that, without prophylaxis, the incidence of DVT is 29%. The risk is particularly high after orthopaedic surgery with an estimated 40% developing DVT and 5% suffering PE. In the absence of malignancy, the lowest risk of VTE is after gynaecological, head and neck and laparoscopic abdominal surgery.
Tom Martin MBBS BSc(Hons) FRCA is a Specialty Registrar at the Bristol School of Anaesthesia, UK. Conflicts of interest: none declared. Caroline Oliver FRCA is a Consultant in Anaesthesia and Critical Care at Frenchay Hospital, Bristol, UK. Her special interest is neuroanaesthesia and critical care. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
Malignancy or cancer treatment Obesity (body mass index 30 kg/m2) Pregnancy and puerperium Acute medical illness Recent myocardial infarction or stroke Major surgery Trauma (major or lower extremity) Immobility Increasing age Inflammatory bowel disease
580
Ó 2009 Elsevier Ltd. All rights reserved.
PERIOPERATIVE CARE
Mechanical
Virchow’s Triad
Graduated compression stockings (GCS) are specifically profiled to exert decreasing circumferential pressure on the leg towards the pelvis, thus creating a pressure gradient favouring venous return from the foot (the Sigel profile). They may be used throughout the perioperative period although should not be used for patients with severe peripheral vascular disease (ankle:brachial pressure index <0.8), peripheral neuropathy or gross limb oedema. As a sole intervention the use of GCS reduces the risk of DVT by 51%. If used in combination with a pharmacological method, the risk is reduced by 56% compared to pharmacological methods alone. Intermittent pneumatic compression (IPC) of the lower leg works on a similar principle by the sequential inflation of bladders within a cuff applied around the calf. As well as reducing venous stasis these devices are thought to stimulate fibrinolytic activity. As a sole intervention they are no more effective than GCS, but, when combined with another non-mechanical method of prophylaxis, they have been shown to reduce the incidence of PE by 50%. Foot impulse devices are an alternative for cases where GCS or IPC are unsuitable. These apply a short and rapid impulse of pressure to the foot. This compresses the venous plexus of the sole displacing blood into the deep veins of the leg and mimicking the effect of weight bearing. These devices may be slightly more effective than GCS or IPC in reducing the risk of DVT. A combination of mechanical methods may confer some additional protection against DVT. Although these techniques are an important part of preventing VTE, it must not be forgotten that the mainstay of mechanical prophylaxis is enabling and encouraging early mobilization after surgery.
Hypocoagulability • Major sugery/trauma • Pregnancy • Osetrogen therapy • Malignancy • Inherited thrombophilia
Venous thromboembolism
Change in blood flow • Immobility • Obesity • Pregnancy
Altered vessel wall • Trauma • Thrombophlebitis • Cellulitis
Figure 1
Definitive diagnosis rests on demonstration of a filling defect during CT pulmonary angiography.
Prevention of VTE Pharmacological
No single technique can completely abolish VTE as a complication of surgery. Instead, a range of mechanical and pharmacological interventions may be used, based on preoperative risk stratification (Table 1).
Heparin Unfractionated heparin (UFH) inhibits coagulation by indirectly inhibiting thrombin via a number of mechanisms. Low molecular
Guidelines from the American College of Chest Physicians for prevention of VTE (2008)2 Level of risk Low risk - Minor surgery in mobile patients - Medical patients who are fully mobile Moderate risk - Most general, open gynaecological or urological procedures - Medical patients, bed rest or sick - Moderate VTE risk plus high bleeding risk High risk - Hip or knee arthroplasty, HFS, major trauma, SCI
DVT risk without thromboprophylaxis (%)
Suggested thromboprophylaxis options
<10
No specific thromboprophylaxis. Early and ‘aggressive’ ambulation
10e40
LMWH or fondaparinux
Mechanical thromboprophylaxis 40e80
LMWH, fondaparinux or oral vitamin K antagonist (INR 2e3) plus mechanical thromboprophylaxis Mechanical thromboprophylaxis
- High VTE risk plus high bleeding risk
LMWH, low molecular weight heparin; INR, International Normalized Ratio; HFS, hip fracture surgery; SCI, spinal cord injury.
Modified, with permission, from Geerts WH et al.2 Table 1
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
581
Ó 2009 Elsevier Ltd. All rights reserved.
PERIOPERATIVE CARE
Hip- and knee- replacement surgery
weight heparin (LMWH) acts predominantly by the inhibition of Factor Xa which catalyses conversion of prothrombin to thrombin. In contrast to UFH, prophylaxis with LMWH is more effective at preventing VTE and may be given once daily. In addition, there is reduced incidence of heparin-induced thrombocytopoenia (HIT) and a lower incidence of bleeding. As a result, LMWH has become the mainstay of pharmacological thromboprophylaxis and should be considered for all but the most straightforward procedures. The use of LMWH combined with a mechanical intervention reduces risk of DVT by 71%.
This constitutes the greatest risk of perioperative VTE after elective surgery. Accordingly, these patients benefit from thromboprophylaxis that extends beyond hospital discharge. The logistical difficulties of managing LMWH administration outside hospital have been recently overcome by the development of a number of directly acting oral anticoagulants. Dabigatran and rivaroxaban Dabigatran is an oral direct thrombin inhibitor. Rivaroxaban is a direct Factor Xa inhibitor. Each has been recently recommended for the primary prevention of VTE following total hip- or kneereplacement surgery.3,4 Treatment should continue for two weeks following knee replacement and five weeks following hip replacement. Each are at least as effective as LMWH in preventing VTE but may be associated with greater risk of significant bleeding.
Aspirin Aspirin inhibits platelet function by irreversible inhibition of cyclooxygenase-1 (COX-1). Although it has some efficacy in reducing the risk of VTE in surgical patients, it is less effective than LMWH and may be associated with more bleeding events. There appears to be no additional benefit in combining aspirin with LMWH.
Anaesthesia and VTE
Warfarin Adjusted-dose warfarin therapy reduces the risk of DVT and PE and its efficacy is comparable to aspirin. However, it requires careful dosing and regular monitoring in addition to significantly increasing risk of major bleeding. As such it is not practical for routine prevention of VTE in the perioperative population.
A number of anaesthetic interventions may reduce the risk of perioperative VTE. When positioning patients for surgery, useful measures include the use of heel pads to avoid calf vein compression and the elevation of limbs to promote venous return. IPC devices are ideally suited for use during general anaesthesia. Avoidance of dehydration reduces the risk of hypercoagulability. The sole use of neuraxial blockade has been associated with a reduction in post-operative VTE after hip surgery. This benefit appears to be lost when a combined technique is used. It is suggested that other regional techniques may carry similar advantages. However, it is important to consider the timing of anticoagulation in relation to any regional technique, in particular, neuraxial blockade. A
Dextrans Dextrans inhibit red cell and platelet adhesion as well as potentiating antithrombin. Preparations of large molecular weight dextrans (e.g. dextran 60 or 70) are poorly excreted and may exert an antithrombotic action that lasts for several days. They are administered as a colloid and must be given in volumes exceeding 1.5 l in order to achieve an anticoagulant effect. Their use may be complicated by allergic reactions in up to 4% of patients and their efficacy of VTE prevention is comparable to aspirin. For these reasons they are rarely used for this indication alone.
REFERENCES 1 NICE Clinical guideline 46. Reducing the risk of venous thromboembolism in inpatients undergoing surgery. National Institute of Clinical Excellence; April 2007. 2 Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism; American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 381Se453. 3 NICE technology appraisal guidance 157. Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. National Institute of Clinical Excellence; September 2008. 4 NICE technology appraisal guidance 170. Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. National Institute of Clinical Excellence; April 2009.
Fondaparinux Fondaparinux is an antithrombin activator and thereby selectively inhibits Factor Xa. It exerts a similar anticoagulant effect to heparin but without the risk of HIT, making it an alternative for patients unable to take LMWH. Danaparoid and lepirudin Danaparoid inhibits Factors Xa and IIa and has an anticoagulant action similar to LMWH. Lepirudin is a direct thrombin inhibitor. Both are licensed for prevention of VTE in patients with HIT.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 10:12
582
Ó 2009 Elsevier Ltd. All rights reserved.