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Deep Vein Thrombosis
CHAPTER 50
DEEP VEIN THROMBOSIS Alejandro Perez, MD, FSVM, RPVI, and Geno J. Merli, MD, FACP, FHM, FSVM 1. W hat three primary factors promote venous thromboembolic (VTE) disease? Development of venous thrombosis is promoted by the following (the Virchow Triad): n Venous blood stasis n Injury to the intimal layer of the venous vasculature n Abnormalities in coagulation or fibrinolysis 2. L ist the risk factors for thromboembolic disease. The numerous risk factors for thromboembolic disease include surgery, trauma, immobility, cancer, pregnancy, prolonged immobilization, estrogen-containing oral contraceptives or hormone replacement therapy, and acute medical illnesses. A more complete listing of these risk factors is given in Box 50-1. 3. W hat is the natural history of venous thrombosis? Resolution of fresh thrombi occurs by endogenous fibrinolysis and organization. Fibrinolysis results in actual clot dissolution. Organization reestablishes venous blood flow by restoring endothelial cells and incorporating into the venous wall residual clot not dissolved by fibrinolysis. Incomplete recanalization can cause postphlebitic syndrome in >20% of patients.
Box 50-1 RISK FACTORS FOR DEEP VENOUS THROMBOEMBOLISM n n n n n n n n n n n n n n n n n n n n n n n
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S urgery Trauma (major or lower extremity) Immobility, lower extremity paresis Cancer (active or occult) Cancer therapy (hormonal, chemotherapy, angiogenesis inhibitors, or radiotherapy) Venous compression (tumor, hematoma, arterial abnormality) Previous history of thromboembolic disease Obesity Pregnancy and postpartum period Prolonged immobilization Lower-extremity or pelvic trauma or surgery Surgery with greater than 30 minutes of general anesthesia Congestive heart failure Nephrotic syndrome Estrogen-containing oral contraceptives or hormone replacement therapy Selective estrogen receptor modulators Inflammatory bowel disease Acute medical illness Myeloproliferative disorders Paroxysmal nocturnal hemoglobinuria Central venous catheter Inherited or acquired thrombophilia Increasing age
DEEP VEIN THROMBOSIS 4. C an patients with deep vein thrombosis (DVT) be accurately diagnosed clinically? No. The clinical diagnosis of DVT is neither sensitive nor specific. Less than 50% of patients with confirmed DVT present with the classic symptoms and signs of DVT, which include pain, tenderness, redness, swelling, and the Homan sign (calf pain with dorsiflexion of the foot). This sole use of clinical findings is artificial, because clinicians couple the medical and surgical history, concomitant medical problems, medications, and risk factors to decide on further testing to confirm DVT. 5. W here is the most common origin for thrombi that result in pulmonary emboli? Thromboses in the deep veins of the lower extremities (Fig. 50-1) account for 90% to 95% of pulmonary emboli. Less common sites of origin include thromboses in the right ventricle, in upper extremity, prostatic, uterine, and renal veins; and, rarely, in superficial veins. 6. H ow is the diagnosis of lower extremity DVT confirmed? Diagnostic evaluation of suspected DVT includes a clear correlation among clinical probability, test selection, and test interpretation. Contrast venography is no longer appropriate as the initial diagnostic test in patients exhibiting DVT symptoms, although it remains the gold standard for confirmatory diagnosis of DVT. It is nearly 100% sensitive and specific and provides the ability to investigate the distal and proximal venous system for thrombosis. Venography is still warranted when noninvasive testing is inconclusive or impossible to perform, but its use is no longer widespread because of the need for administration of a contrast medium and the increased availability of noninvasive diagnostic strategies.
1 2 3
4 5
6 7
Figure 50-1. Common sites of deep venous thrombosis (DVT) in the lower body. 1, Left iliac vein; 2, common femoral vein; 3, termination of deep femoral vein (profunda femoris); 4, femoral vein; 5, popliteal vein at adductor canal; 6, posterior tibial vein; 7, intramuscular veins of calf. (From Pfenninger JL, Fowler GC: Pfenninger and Fowler’s procedures for primary care, ed 3, Philadelphia, 2010, Saunders.)
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Ultrasound is safe and noninvasive and has a higher specificity than impedance plethysmography for the evaluation of suspected DVT. With color flow Doppler and compression ultrasound, DVT is diagnosed based on the inability to compress the common femoral and popliteal veins (Fig. 50-2). In patients with lower extremity symptoms, the sensitivity is 95% and specificity 96%. The diagnostic accuracy of ultrasound in asymptomatic patients, those with recurrent DVT, or those with isolated calf
A A
Non comp
Comp
Figure 50-2. Normal and abnormal compression of the femoral vein with ultrasound examination. Top Images: Transverse image of the femoral artery (A) and vein (thin white arrow) before (Non Comp) and after (Comp) compression with the sonographic transducer, demonstrated normal vein collapse with compression. Bottom Images: There is minimum compression of the common femoral vein (thick white arrow) in this patient with deep vein thrombosis. (Top images from Rumack CM, Wilson SR, Charboneau JW, Levine D: Diagnostic ultrasound, ed 4, Philadelphia, 2010, Mosby. Bottom images from Mason RJ, Broaddus VC, Martin T, et al: Murray and Nadel’s textbook of respiratory medicine, ed 5, Philadelphia, 2010, Saunders.)
DEEP VEIN THROMBOSIS DVT is less reliable. The sensitivity of ultrasound improves with serial testing in untreated patients. Repeat testing at 5 to 7 days will identify another 2% of patients with clots not apparent on the first ultrasound. Serial testing can be particularly valuable in ruling out proximal extension of a possible calf DVT. Because the accuracy of ultrasound in diagnosing calf DVT is acknowledged to be lower (81% for DVT below the knee versus 99% for proximal DVT), follow-up ultrasounds at 5 to 7 days are reasonable because most calf DVTs that extend proximally will do so within days of the initial presentation. 7. W hen should prophylaxis of DVT be considered? Two factors must be weighed in deciding to initiate prophylaxis of DVT: the degree of risk for thrombosis and the risk of prophylaxis. The risk factors for DVT are cumulative. The primary risk of pharmacologic prophylaxis is hemorrhage, which is generally uncommon if no coagulation defects or lesions with bleeding potential exist. 8. W hat prophylactic measures are available? Approaches to prophylaxis of DVT include antithrombotic drugs and pneumatic compression devices. Heparin, low-molecular-weight heparin (LMWH), fondaparinux, and warfarin are effective in preventing DVT. Subcutaneous heparin has been the mainstay of DVT prophylaxis, with efficacy in multiple surgical and medical scenarios. The LMWHs have been shown to be as effective or superior to unfractionated heparin (UFH) in different clinical circumstances. Warfarin dosing to maintain an international normalized ratio (INR) between 2 and 3 also has a low risk of bleeding and is effective in patients with total hip arthroplasty, total knee arthroplasty, and hip fracture surgery. However, warfarin takes several days to develop a full antithrombotic effect. Antiplatelet drugs such as aspirin are not effective in DVT prophylaxis in the general medical population, but aspirin has been used with efficacy in the orthopedic surgery population. Rivaroxaban can also be used for DVT prophylaxis in orthopedic surgeries. Intermittent pneumatic compression devices effect prophylaxis by maintaining venous flow in the lower extremities and are especially efficacious in patients who cannot receive anticoagulant medications. Modalities available include compressive devices applied to the feet alone, covering the calves, or extending to the thighs. No version has been shown to provide superior prophylaxis. There has been concern that compression stockings used for prophylaxis may cause unintended skin trauma without substantial benefit. 9. W hat is the approach to DVT prophylaxis in the hospitalized, medically ill patient? The acutely ill medical patient admitted to the hospital with congestive heart failure or severe respiratory disease, or who is confined to bed and has one or more additional risk factors, including active cancer, previous venous thromboembolism, sepsis, acute neurologic disease, or inflammatory bowel disease, should receive DVT prophylaxis with the following agents: n UFH: 5000 units subcutaneously (SC) every 8 or 12 hours n LMWH: dalteparin: 5000 IU SC every 24 hours or enoxaparin: 40 mg SC every 24 hours n Fondaparinux: 2.5 mg SC every 24 hours 10. S hould patients undergoing surgery receive DVT prophylaxis based on specific recommendations for each respective procedure? Yes. Most surgical procedures have defined recommendations for preventing DVT in the postoperative period if age and other clinical comorbidities demonstrate an elevated risk based upon risk assessment models, such as that of the Rogers or Caprini score. The various prophylaxis regimens for different surgical procedures are listed in Box 50-2. 11. A re there specific surgical groups that require extended DVT prophylaxis following hospital discharge? For a patient undergoing total hip replacement, total knee replacement, and hip fracture surgery, extended DVT prophylaxis is recommended for up to 35 days after surgery, with LMWH, UFH, fondaparinux, warfarin, rivaroxaban, or aspirin.
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Box 50-2 DEEP VEIN THROMBOSIS PROPHYLAXIS REGIMENS FOR VARIOUS SURGERIES General Urologic, Gastrointestinal, Gynecologic, Bariatric, Vascular, Plastic, or Reconstructive Surgery The following regimens are for patients undergoing major surgical procedures for benign or malignant disease and associated DVT risk factors: n Unfractionated heparin: 5000 units SC every 8 hours n LMWH: enoxaparin 40 mg SC every 24 hours, dalteparin 5000 IU SC every 24 hours n External pneumatic compression sleeves plus one of the above regimens n Fondaparinux: 2.5 mg SC, every 24 hours can be considered for patients with history of heparin associated thrombocytopenia. Orthopedic Surgery The following regimens are for patients undergoing orthopedic surgery: Total Hip/Knee Surgery n LMWH: enoxaparin 30 mg SC every 12 hours, dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units SC every 8 hours n Fondaparinux: 2.5 mg SC every 24 hours n Rivaroxaban: 10 mg every 24 hours n ASA: (optimal dose has yet to be determined) n Intermittent pneumatic compression devices n Warfarin: 5 mg the evening of surgery, then adjust dose to achieve an INR of 2 to 3. Hip Fracture n LMWH: enoxaparin 30 mg SC every 12 hours, dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units SC every 8 hours n Fondaparinux: 2.5 mg SC every 24 hours n ASA: (optimal dose has yet to be determined) n Intermittent pneumatic compression devices n Warfarin: 5 mg the evening of surgery, then adjust dose to achieve an INR of 2 to 3. n (Rivaroxaban is not approved for this indication at the time of this writing.) Neurosurgery The following regimens are for patients undergoing neurosurgery: n External pneumatic compression sleeves are the prophylaxis of choice. n Combination therapy with either unfractionated heparin (5000 units SC every 8 or 12 hours) or LMWH (enoxaparin 40 mg SC every 24 hours) can be used. Coronary Artery Bypass Surgery The following regimens are for patients undergoing coronary artery bypass surgery: n LMWH (preferred over unfractionated heparin): enoxaparin 40 mg SC every 24 hours or dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units, SC every 8 hours n Fondaparinux: 2.5 mg, SC, every 24 hours for patients with history of heparin-induced thrombocytopenia n External pneumatic compression sleeves for high–bleeding-risk patients ASA, Aspirin; DVT, deep vein thrombosis; INR, international normalized ratio; IU, international units; LMWH, low-molecular-weight heparin; SC, subcutaneous.
DEEP VEIN THROMBOSIS For selected high-risk general surgery patients undergoing major cancer surgery or who have previously had venous thromboembolism, it is recommended that DVT prophylaxis be continued with LMWH: enoxaparin 40 mg SC every 24 hours or dalteparin 5000 IU SC every 24 hours for 35 days. 12. W hat treatment regimens are available for the treatment of DVT? Several treatment regimens using UFH or a LMWH are available for the treatment of DVT. These are listed in Box 50-3. 13. W hich LMWHs are renally excreted? All the LMWHs are renally excreted. Enoxaparin is the only LMWH that has a recommended dose for creatinine clearance less than 30 mL/min (1 mg/kg SC every 24 hours). All other LMWHs listed here should not be used with creatinine clearance less than 30 mL/min. 14. W hen should warfarin be started with the regimens of treatment of DVT listed earlier? In patients with acute DVT, warfarin should be administered on the first day of UFH or LMWH treatment at a dose of 5 to 10 mg. 15. W hen should these therapeutic regimens for treating DVT be discontinued and warfarin remain as the sole therapy? These therapies must be used for at least 5 days and until the INR is more than 2 for 24 hours. 16. W hat is the target INR for treating patients with DVT? The target INR for the treatment of DVT to prevent recurrent disease is 2 to 3. 17. H ow long should patients with acute DVT be treated with warfarin? For patients with DVT secondary to a transient risk factor, 3 months of warfarin is appropriate. Idiopathic proximal DVT in patients without risk factors for bleeding should receive long-term warfarin therapy with a target INR of 2 to 3. Patients with DVT and cancer should receive LMWH for 3 to 6 months as the initial approach to management and long-term treatment with either warfarin or LMWH until the cancer is resolved or in remission.
Box 50-3 REGIMENS FOR THE TREATMENT OF DEEP VEIN THROMBOSIS Unfractionated Heparin (UFH) n Administer intravenous bolus of UFH (80 units/kg or 5000 units) followed by continuous infusion of 18 unit/kg/hr or 1000 units/hr. The activated partial thromboplastin time (aPTT) is checked every 6 hours to adjust the infusion to achieve the therapeutic aPTT of the hospital laboratory. n Subcutaneous UFH at 333 units/kg is the initial dose, followed in 12 hours by 250 units/kg SC every 12 hours. Monitoring of the aPTT is not necessary. Low-Molecular-Weight Heparin (LMWH) n Enoxaparin 1 mg/kg subcutaneous (SC), every 12 hours or 1.5 mg/kg SC every 24 hours n Dalteparin 200 units/kg SC every 24 hours n Tinzaparin 175 anti-Xa units/kg SC every 24 hours Fondaparinux n Fondaparinux dosed by weight range: less than 50 kg, 5 mg SC every 24 hours; 50 to 100 kg, 7.5 mg SC every 24 hours; more than 100 kg, 10 mg SC every 24 hours
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DEEP VEIN THROMBOSIS 18. W hen can patients with acute DVT ambulate? Patients can ambulate with acute DVT and should not be placed on bed rest unless the lower extremity is painful and cannot bear weight. 19. C an patients with acute DVT be treated as outpatients? Yes. The LMWH regimens listed here can be used to treat patients in the outpatient setting. The same principles of management should be followed using these agents as with inpatient treatment. 20. W hen should catheter-directed thrombolysis be used to treat acute DVT? In selected patients with extensive acute proximal iliofemoral DVT in which symptoms have been present for less than 14 days, who are functionally active, and who have a low bleeding risk, the use of pharmacomechanical thrombolysis is recommended if the appropriate expertise and resources are available. 21. A re inferior vena caval filters indicated for the initial treatment of acute DVT? No. Vena caval filters are indicated when the patient cannot receive anticoagulation for the treatment of acute DVT. In certain cases (temporary contraindication to anticoagulant therapy), retrievable vena caval filters have been placed, with the plan to remove them in a defined time (2 to 4 weeks), after which anticoagulation therapy can be reinstituted. 22. W hen are gradient elastic stockings recommended as part of the treatment of acute DVT? For patients with symptomatic DVT, the use of gradient elastic stockings with an ankle pressure of 30 to 40 mm Hg is recommended. The pressure may not be tolerated because of the degree of lowerextremity edema. Elastic bandages may be used because they can be adjusted to control swelling and the pain that is associated with increased external pressure. The elastic bandages can be used initially, but as the swelling recedes, gradient elastic stockings at 20 to 30 mm Hg or 30 to 40 mm Hg may be applied. 23. W hen is a low-intensity INR anticoagulant therapy indicated for the treatment of DVT? For patients with idiopathic (unprovoked) DVT who have a strong preference for less frequent INR testing to monitor their therapy, it is recommended that after the first 3 months of therapy, lowintensity therapy at an INR of 1.5 to 1.9 with less frequent INR monitoring be employed instead of stopping warfarin anticoagulation. 24. A re there other INR ranges for DVT prophylaxis in orthopedic surgery? Other target ranges such as 1.5-2.0 have been proposed for orthopedic surgery prophylaxis, but the INR range 2-3 has the most supportive clinical data. 25. S hould compression ultrasound be used as routine screening in the total joint replacement surgery patient at the time of discharge? Asymptomatic joint replacement surgery patients should not have compression ultrasound on discharge as screening test for DVT because the ultrasound is not as sensitive and specific in asymptomatic patients. Appropriate DVT prophylaxis should be the approach to management.
BIBLIOGRAPHY, SUGGESTED READINGS, AND WEBSITES 1. British Thoracic Society Standards of Care Committee: Pulmonary Embolism Guideline Development Group: British Thoracic Society guidelines for the management of suspected acute pulmonary embolism, Thorax 58:470–483, 2003. 2. Cardiovascular Disease Educational and Research Trust, Cyprus Cardiovascular Disease Educational and Research Trust, European Venous Forum, et al: Prevention and treatment of venous thromboembolism. International consensus statement (guidelines according to scientific evidence), Int Angiol 25:101–161, 2006.
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3. Decousus H, Leizorovicz A, Parent F, et al: A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis, N Engl J Med 338:409–415, 1998. 4. Gould MK, Garcia DA, Wren SM, et al: Prevention of VTE in Nonorthopedic Surgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e227S–e277S, 2012. 5. Kahn SR, Lim W, Dunn AS, et al: Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e195S–e226S, 2012. 6. Kearon C, Ginsberg JS, Julian JA, et al: Comparison of fixed-dose weight adjusted unfractionated heparin and lowmolecular weight heparin for acute treatment of venous thromboembolism, JAMA 296:935–942, 2006. 7. Koopman MM, Prandoni P, Piovella F, et al: Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home, N Engl J Med 334:682–687, 1996. 8. Levine M, Gent M, Hirsh J, et al: A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis, N Engl J Med 334:677–681, 1996. 9. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism, N Engl J Med 349:1695–1702, 2003. 10. Merli GJ: Pathophysiology of venous thrombosis and the diagnosis of deep vein thrombosis-pulmonary embolism in the elderly, Cardiol Clin 26:203–219, 2008. 11. Merli G, Spiro T, Olsson CG, et al: Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease, Ann Intern Med 134:191–202, 2001. 12. Snow V, Qaseem A, Barry P, et al: Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians, Ann Intern Med 146(3):204–210, 2007. 13. Wells PS, Anderson DR, Rodger MA, et al: A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism, Arch Intern Med 165:733–738, 2005. 14. Falck-Ytter Y, Francis CW, Johanson NA, et al: Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e278S–e325S, 2012.
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DEEP VEIN THROMBOSIS Alejandro Perez, MD, FSVM, RPVI, and Geno J. Merli, MD, FACP, FHM, FSVM 1. W hat three primary factors promote venous thromboembolic (VTE) disease? Development of venous thrombosis is promoted by the following (the Virchow Triad): n Venous blood stasis n Injury to the intimal layer of the venous vasculature n Abnormalities in coagulation or fibrinolysis 2. L ist the risk factors for thromboembolic disease. The numerous risk factors for thromboembolic disease include surgery, trauma, immobility, cancer, pregnancy, prolonged immobilization, estrogen-containing oral contraceptives or hormone replacement therapy, and acute medical illnesses. A more complete listing of these risk factors is given in Box 50-1. 3. W hat is the natural history of venous thrombosis? Resolution of fresh thrombi occurs by endogenous fibrinolysis and organization. Fibrinolysis results in actual clot dissolution. Organization reestablishes venous blood flow by restoring endothelial cells and incorporating into the venous wall residual clot not dissolved by fibrinolysis. Incomplete recanalization can cause postphlebitic syndrome in >20% of patients.
Box 50-1 RISK FACTORS FOR DEEP VENOUS THROMBOEMBOLISM n n n n n n n n n n n n n n n n n n n n n n n
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S urgery Trauma (major or lower extremity) Immobility, lower extremity paresis Cancer (active or occult) Cancer therapy (hormonal, chemotherapy, angiogenesis inhibitors, or radiotherapy) Venous compression (tumor, hematoma, arterial abnormality) Previous history of thromboembolic disease Obesity Pregnancy and postpartum period Prolonged immobilization Lower-extremity or pelvic trauma or surgery Surgery with greater than 30 minutes of general anesthesia Congestive heart failure Nephrotic syndrome Estrogen-containing oral contraceptives or hormone replacement therapy Selective estrogen receptor modulators Inflammatory bowel disease Acute medical illness Myeloproliferative disorders Paroxysmal nocturnal hemoglobinuria Central venous catheter Inherited or acquired thrombophilia Increasing age
DEEP VEIN THROMBOSIS 4. C an patients with deep vein thrombosis (DVT) be accurately diagnosed clinically? No. The clinical diagnosis of DVT is neither sensitive nor specific. Less than 50% of patients with confirmed DVT present with the classic symptoms and signs of DVT, which include pain, tenderness, redness, swelling, and the Homan sign (calf pain with dorsiflexion of the foot). This sole use of clinical findings is artificial, because clinicians couple the medical and surgical history, concomitant medical problems, medications, and risk factors to decide on further testing to confirm DVT. 5. W here is the most common origin for thrombi that result in pulmonary emboli? Thromboses in the deep veins of the lower extremities (Fig. 50-1) account for 90% to 95% of pulmonary emboli. Less common sites of origin include thromboses in the right ventricle, in upper extremity, prostatic, uterine, and renal veins; and, rarely, in superficial veins. 6. H ow is the diagnosis of lower extremity DVT confirmed? Diagnostic evaluation of suspected DVT includes a clear correlation among clinical probability, test selection, and test interpretation. Contrast venography is no longer appropriate as the initial diagnostic test in patients exhibiting DVT symptoms, although it remains the gold standard for confirmatory diagnosis of DVT. It is nearly 100% sensitive and specific and provides the ability to investigate the distal and proximal venous system for thrombosis. Venography is still warranted when noninvasive testing is inconclusive or impossible to perform, but its use is no longer widespread because of the need for administration of a contrast medium and the increased availability of noninvasive diagnostic strategies.
1 2 3
4 5
6 7
Figure 50-1. Common sites of deep venous thrombosis (DVT) in the lower body. 1, Left iliac vein; 2, common femoral vein; 3, termination of deep femoral vein (profunda femoris); 4, femoral vein; 5, popliteal vein at adductor canal; 6, posterior tibial vein; 7, intramuscular veins of calf. (From Pfenninger JL, Fowler GC: Pfenninger and Fowler’s procedures for primary care, ed 3, Philadelphia, 2010, Saunders.)
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Ultrasound is safe and noninvasive and has a higher specificity than impedance plethysmography for the evaluation of suspected DVT. With color flow Doppler and compression ultrasound, DVT is diagnosed based on the inability to compress the common femoral and popliteal veins (Fig. 50-2). In patients with lower extremity symptoms, the sensitivity is 95% and specificity 96%. The diagnostic accuracy of ultrasound in asymptomatic patients, those with recurrent DVT, or those with isolated calf
A A
Non comp
Comp
Figure 50-2. Normal and abnormal compression of the femoral vein with ultrasound examination. Top Images: Transverse image of the femoral artery (A) and vein (thin white arrow) before (Non Comp) and after (Comp) compression with the sonographic transducer, demonstrated normal vein collapse with compression. Bottom Images: There is minimum compression of the common femoral vein (thick white arrow) in this patient with deep vein thrombosis. (Top images from Rumack CM, Wilson SR, Charboneau JW, Levine D: Diagnostic ultrasound, ed 4, Philadelphia, 2010, Mosby. Bottom images from Mason RJ, Broaddus VC, Martin T, et al: Murray and Nadel’s textbook of respiratory medicine, ed 5, Philadelphia, 2010, Saunders.)
DEEP VEIN THROMBOSIS DVT is less reliable. The sensitivity of ultrasound improves with serial testing in untreated patients. Repeat testing at 5 to 7 days will identify another 2% of patients with clots not apparent on the first ultrasound. Serial testing can be particularly valuable in ruling out proximal extension of a possible calf DVT. Because the accuracy of ultrasound in diagnosing calf DVT is acknowledged to be lower (81% for DVT below the knee versus 99% for proximal DVT), follow-up ultrasounds at 5 to 7 days are reasonable because most calf DVTs that extend proximally will do so within days of the initial presentation. 7. W hen should prophylaxis of DVT be considered? Two factors must be weighed in deciding to initiate prophylaxis of DVT: the degree of risk for thrombosis and the risk of prophylaxis. The risk factors for DVT are cumulative. The primary risk of pharmacologic prophylaxis is hemorrhage, which is generally uncommon if no coagulation defects or lesions with bleeding potential exist. 8. W hat prophylactic measures are available? Approaches to prophylaxis of DVT include antithrombotic drugs and pneumatic compression devices. Heparin, low-molecular-weight heparin (LMWH), fondaparinux, and warfarin are effective in preventing DVT. Subcutaneous heparin has been the mainstay of DVT prophylaxis, with efficacy in multiple surgical and medical scenarios. The LMWHs have been shown to be as effective or superior to unfractionated heparin (UFH) in different clinical circumstances. Warfarin dosing to maintain an international normalized ratio (INR) between 2 and 3 also has a low risk of bleeding and is effective in patients with total hip arthroplasty, total knee arthroplasty, and hip fracture surgery. However, warfarin takes several days to develop a full antithrombotic effect. Antiplatelet drugs such as aspirin are not effective in DVT prophylaxis in the general medical population, but aspirin has been used with efficacy in the orthopedic surgery population. Rivaroxaban can also be used for DVT prophylaxis in orthopedic surgeries. Intermittent pneumatic compression devices effect prophylaxis by maintaining venous flow in the lower extremities and are especially efficacious in patients who cannot receive anticoagulant medications. Modalities available include compressive devices applied to the feet alone, covering the calves, or extending to the thighs. No version has been shown to provide superior prophylaxis. There has been concern that compression stockings used for prophylaxis may cause unintended skin trauma without substantial benefit. 9. W hat is the approach to DVT prophylaxis in the hospitalized, medically ill patient? The acutely ill medical patient admitted to the hospital with congestive heart failure or severe respiratory disease, or who is confined to bed and has one or more additional risk factors, including active cancer, previous venous thromboembolism, sepsis, acute neurologic disease, or inflammatory bowel disease, should receive DVT prophylaxis with the following agents: n UFH: 5000 units subcutaneously (SC) every 8 or 12 hours n LMWH: dalteparin: 5000 IU SC every 24 hours or enoxaparin: 40 mg SC every 24 hours n Fondaparinux: 2.5 mg SC every 24 hours 10. S hould patients undergoing surgery receive DVT prophylaxis based on specific recommendations for each respective procedure? Yes. Most surgical procedures have defined recommendations for preventing DVT in the postoperative period if age and other clinical comorbidities demonstrate an elevated risk based upon risk assessment models, such as that of the Rogers or Caprini score. The various prophylaxis regimens for different surgical procedures are listed in Box 50-2. 11. A re there specific surgical groups that require extended DVT prophylaxis following hospital discharge? For a patient undergoing total hip replacement, total knee replacement, and hip fracture surgery, extended DVT prophylaxis is recommended for up to 35 days after surgery, with LMWH, UFH, fondaparinux, warfarin, rivaroxaban, or aspirin.
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Box 50-2 DEEP VEIN THROMBOSIS PROPHYLAXIS REGIMENS FOR VARIOUS SURGERIES General Urologic, Gastrointestinal, Gynecologic, Bariatric, Vascular, Plastic, or Reconstructive Surgery The following regimens are for patients undergoing major surgical procedures for benign or malignant disease and associated DVT risk factors: n Unfractionated heparin: 5000 units SC every 8 hours n LMWH: enoxaparin 40 mg SC every 24 hours, dalteparin 5000 IU SC every 24 hours n External pneumatic compression sleeves plus one of the above regimens n Fondaparinux: 2.5 mg SC, every 24 hours can be considered for patients with history of heparin associated thrombocytopenia. Orthopedic Surgery The following regimens are for patients undergoing orthopedic surgery: Total Hip/Knee Surgery n LMWH: enoxaparin 30 mg SC every 12 hours, dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units SC every 8 hours n Fondaparinux: 2.5 mg SC every 24 hours n Rivaroxaban: 10 mg every 24 hours n ASA: (optimal dose has yet to be determined) n Intermittent pneumatic compression devices n Warfarin: 5 mg the evening of surgery, then adjust dose to achieve an INR of 2 to 3. Hip Fracture n LMWH: enoxaparin 30 mg SC every 12 hours, dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units SC every 8 hours n Fondaparinux: 2.5 mg SC every 24 hours n ASA: (optimal dose has yet to be determined) n Intermittent pneumatic compression devices n Warfarin: 5 mg the evening of surgery, then adjust dose to achieve an INR of 2 to 3. n (Rivaroxaban is not approved for this indication at the time of this writing.) Neurosurgery The following regimens are for patients undergoing neurosurgery: n External pneumatic compression sleeves are the prophylaxis of choice. n Combination therapy with either unfractionated heparin (5000 units SC every 8 or 12 hours) or LMWH (enoxaparin 40 mg SC every 24 hours) can be used. Coronary Artery Bypass Surgery The following regimens are for patients undergoing coronary artery bypass surgery: n LMWH (preferred over unfractionated heparin): enoxaparin 40 mg SC every 24 hours or dalteparin 5000 IU SC every 24 hours n Unfractionated heparin: 5000 units, SC every 8 hours n Fondaparinux: 2.5 mg, SC, every 24 hours for patients with history of heparin-induced thrombocytopenia n External pneumatic compression sleeves for high–bleeding-risk patients ASA, Aspirin; DVT, deep vein thrombosis; INR, international normalized ratio; IU, international units; LMWH, low-molecular-weight heparin; SC, subcutaneous.
DEEP VEIN THROMBOSIS For selected high-risk general surgery patients undergoing major cancer surgery or who have previously had venous thromboembolism, it is recommended that DVT prophylaxis be continued with LMWH: enoxaparin 40 mg SC every 24 hours or dalteparin 5000 IU SC every 24 hours for 35 days. 12. W hat treatment regimens are available for the treatment of DVT? Several treatment regimens using UFH or a LMWH are available for the treatment of DVT. These are listed in Box 50-3. 13. W hich LMWHs are renally excreted? All the LMWHs are renally excreted. Enoxaparin is the only LMWH that has a recommended dose for creatinine clearance less than 30 mL/min (1 mg/kg SC every 24 hours). All other LMWHs listed here should not be used with creatinine clearance less than 30 mL/min. 14. W hen should warfarin be started with the regimens of treatment of DVT listed earlier? In patients with acute DVT, warfarin should be administered on the first day of UFH or LMWH treatment at a dose of 5 to 10 mg. 15. W hen should these therapeutic regimens for treating DVT be discontinued and warfarin remain as the sole therapy? These therapies must be used for at least 5 days and until the INR is more than 2 for 24 hours. 16. W hat is the target INR for treating patients with DVT? The target INR for the treatment of DVT to prevent recurrent disease is 2 to 3. 17. H ow long should patients with acute DVT be treated with warfarin? For patients with DVT secondary to a transient risk factor, 3 months of warfarin is appropriate. Idiopathic proximal DVT in patients without risk factors for bleeding should receive long-term warfarin therapy with a target INR of 2 to 3. Patients with DVT and cancer should receive LMWH for 3 to 6 months as the initial approach to management and long-term treatment with either warfarin or LMWH until the cancer is resolved or in remission.
Box 50-3 REGIMENS FOR THE TREATMENT OF DEEP VEIN THROMBOSIS Unfractionated Heparin (UFH) n Administer intravenous bolus of UFH (80 units/kg or 5000 units) followed by continuous infusion of 18 unit/kg/hr or 1000 units/hr. The activated partial thromboplastin time (aPTT) is checked every 6 hours to adjust the infusion to achieve the therapeutic aPTT of the hospital laboratory. n Subcutaneous UFH at 333 units/kg is the initial dose, followed in 12 hours by 250 units/kg SC every 12 hours. Monitoring of the aPTT is not necessary. Low-Molecular-Weight Heparin (LMWH) n Enoxaparin 1 mg/kg subcutaneous (SC), every 12 hours or 1.5 mg/kg SC every 24 hours n Dalteparin 200 units/kg SC every 24 hours n Tinzaparin 175 anti-Xa units/kg SC every 24 hours Fondaparinux n Fondaparinux dosed by weight range: less than 50 kg, 5 mg SC every 24 hours; 50 to 100 kg, 7.5 mg SC every 24 hours; more than 100 kg, 10 mg SC every 24 hours
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DEEP VEIN THROMBOSIS 18. W hen can patients with acute DVT ambulate? Patients can ambulate with acute DVT and should not be placed on bed rest unless the lower extremity is painful and cannot bear weight. 19. C an patients with acute DVT be treated as outpatients? Yes. The LMWH regimens listed here can be used to treat patients in the outpatient setting. The same principles of management should be followed using these agents as with inpatient treatment. 20. W hen should catheter-directed thrombolysis be used to treat acute DVT? In selected patients with extensive acute proximal iliofemoral DVT in which symptoms have been present for less than 14 days, who are functionally active, and who have a low bleeding risk, the use of pharmacomechanical thrombolysis is recommended if the appropriate expertise and resources are available. 21. A re inferior vena caval filters indicated for the initial treatment of acute DVT? No. Vena caval filters are indicated when the patient cannot receive anticoagulation for the treatment of acute DVT. In certain cases (temporary contraindication to anticoagulant therapy), retrievable vena caval filters have been placed, with the plan to remove them in a defined time (2 to 4 weeks), after which anticoagulation therapy can be reinstituted. 22. W hen are gradient elastic stockings recommended as part of the treatment of acute DVT? For patients with symptomatic DVT, the use of gradient elastic stockings with an ankle pressure of 30 to 40 mm Hg is recommended. The pressure may not be tolerated because of the degree of lowerextremity edema. Elastic bandages may be used because they can be adjusted to control swelling and the pain that is associated with increased external pressure. The elastic bandages can be used initially, but as the swelling recedes, gradient elastic stockings at 20 to 30 mm Hg or 30 to 40 mm Hg may be applied. 23. W hen is a low-intensity INR anticoagulant therapy indicated for the treatment of DVT? For patients with idiopathic (unprovoked) DVT who have a strong preference for less frequent INR testing to monitor their therapy, it is recommended that after the first 3 months of therapy, lowintensity therapy at an INR of 1.5 to 1.9 with less frequent INR monitoring be employed instead of stopping warfarin anticoagulation. 24. A re there other INR ranges for DVT prophylaxis in orthopedic surgery? Other target ranges such as 1.5-2.0 have been proposed for orthopedic surgery prophylaxis, but the INR range 2-3 has the most supportive clinical data. 25. S hould compression ultrasound be used as routine screening in the total joint replacement surgery patient at the time of discharge? Asymptomatic joint replacement surgery patients should not have compression ultrasound on discharge as screening test for DVT because the ultrasound is not as sensitive and specific in asymptomatic patients. Appropriate DVT prophylaxis should be the approach to management.
BIBLIOGRAPHY, SUGGESTED READINGS, AND WEBSITES 1. British Thoracic Society Standards of Care Committee: Pulmonary Embolism Guideline Development Group: British Thoracic Society guidelines for the management of suspected acute pulmonary embolism, Thorax 58:470–483, 2003. 2. Cardiovascular Disease Educational and Research Trust, Cyprus Cardiovascular Disease Educational and Research Trust, European Venous Forum, et al: Prevention and treatment of venous thromboembolism. International consensus statement (guidelines according to scientific evidence), Int Angiol 25:101–161, 2006.
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3. Decousus H, Leizorovicz A, Parent F, et al: A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis, N Engl J Med 338:409–415, 1998. 4. Gould MK, Garcia DA, Wren SM, et al: Prevention of VTE in Nonorthopedic Surgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e227S–e277S, 2012. 5. Kahn SR, Lim W, Dunn AS, et al: Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e195S–e226S, 2012. 6. Kearon C, Ginsberg JS, Julian JA, et al: Comparison of fixed-dose weight adjusted unfractionated heparin and lowmolecular weight heparin for acute treatment of venous thromboembolism, JAMA 296:935–942, 2006. 7. Koopman MM, Prandoni P, Piovella F, et al: Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home, N Engl J Med 334:682–687, 1996. 8. Levine M, Gent M, Hirsh J, et al: A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis, N Engl J Med 334:677–681, 1996. 9. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism, N Engl J Med 349:1695–1702, 2003. 10. Merli GJ: Pathophysiology of venous thrombosis and the diagnosis of deep vein thrombosis-pulmonary embolism in the elderly, Cardiol Clin 26:203–219, 2008. 11. Merli G, Spiro T, Olsson CG, et al: Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease, Ann Intern Med 134:191–202, 2001. 12. Snow V, Qaseem A, Barry P, et al: Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians, Ann Intern Med 146(3):204–210, 2007. 13. Wells PS, Anderson DR, Rodger MA, et al: A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism, Arch Intern Med 165:733–738, 2005. 14. Falck-Ytter Y, Francis CW, Johanson NA, et al: Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(Suppl 2):e278S–e325S, 2012.
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