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Venous Thromboembolism in Oral and Maxillofacial Surgery: A Review of the Literature
J Oral Maxillofac Surg 69:840-844, 2011
Venous Thromboembolism in Oral and Maxillofacial Surgery: A Review of the Literature Bryce Williams, DDS,* A. Thomas Indresano, DMD,† and Felice O’Ryan, DDS‡ Background
Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism, or a combination of both, is among the most common complication in hospitalized patients, with an estimated 900,000 cases occurring annually.1 Pulmonary embolism resulting from DVT is the leading cause of preventable hospital deaths.2 In over 7 million patients discharged from acute care hospitals in the United States, VTE was the second most common medical complication, the second most common cause of increased length of hospital stay, the third most common cause of mortality and a significant increase in financial cost.3 Although disagreement exists regarding risk classification of thromboembolism in hospitalized individuals, most of these patients have at least 1 risk factor for VTE and almost one half have 3 or more risk factors.4 With the continually expanding surgical scope and treatment of medically complex patients in the contemporary oral maxillofacial surgical practice, it is imperative to be aware of the risk factors for VTE and implement evidence-based thromboprophylaxis strategies. This article reviews classic and current literature regarding the pathophysiology, risk factors, and prophylaxis of venous thromboembolism in an effort to increase awareness of this potentially devastating complication.
Clinical signs of DVT are thought to have been first described by the Indian surgeon Susruta between 600 and 1000 BC, who observed a patient with a “swollen and painful leg, which was difficult to treat.”5 In the 18th and 19th centuries European anatomists Giovanni Battista Morgagni (1761) and later Jean Cruveilhier (1849) discovered clots in the pulmonary vasculature of cadavers that they postulated were related to an inflammatory process.5 Cruveilhier’s frequently repeated phrase, “La phlebite domine toute la pathologie” (“phlebitis dominates all of pathology”), was an expression familiar to Rudolf Virchow, a German physician studying the pathology of thrombosis.6 By 1856, Virchow had postulated the pathophysiology of thromboembolism, which was later termed “Virchow’s triad.” This triad now refers to 3 components important in thrombogenesis: venous stasis, endothelial damage, and hypercoagulability.7 Several risk factors in surgical patients, either acquired or inherent, may increase the probability of occurrence of any or all of the components of Virchow’s triad.
Pathophysiology Venous stasis, aggravated by immobilization, is among the most important risk factors for thrombotic events in hospitalized patients. Stagnation of venous blood creates local hypoxia, which directly activates clotting factors, particularly factor X.8 In the surgical patient, intraoperative venous dilation and distension, due to the effects of anesthesia, are thought to be additional factors contributing to venous stasis.9-13 Endothelial damage, which activates both intrinsic and extrinsic coagulation pathways, may be the result of direct (trauma or surgery) or indirect injury (sepsis, vasculitis, chemotherapy).14 Vascular wall injury causes release of coagulation factors and exposure of underlying collagen, which in turn induces platelet adhesion and subsequent aggregation.9,11 Acute vessel trauma reduces endothelial cell production of tissue plasminogen activator, further contributing to thrombus formation.15 Tissue factor (CF VII), also stimulated by endothelial damage, triggers the extrinsic coagulation pathway.
*Resident, Department of Oral and Maxillofacial Surgery, University of the Pacific/Highland Hospital, Oakland, CA. †Director, Department of Oral and Maxillofacial Surgery, University of the Pacific/Highland Hospital, Oakland, CA. ‡Division of Maxillofacial Surgery, Kaiser Permanente, Oakland Medical Center, Oakland, CA. Address correspondence and reprint requests to Dr O’Ryan: Kaiser Permanente Division of Maxillofacial Surgery, 280 West MacArthur Blvd, Oakland, CA 94611; e-mail: Felice.O’[email protected] © 2011 American Association of Oral and Maxillofacial Surgeons
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The third feature of Virchow’s triad, hypercoagulability, is related to a number of genetic and acquired characteristics; with heritable coagulopathies, malignancies, oral contraceptives, or hormone replacement therapy being the more common predisposing factors.4,5,10 The factor V Leiden gene, the most common hereditary thrombophilia, occurs in 5% to 15% of the general population, and the homozygous form increases the risk of DVT sixfold.16 Other congenital thrombophilic disorders, including prothrombin G20210A, and elevated levels of factors VII, IX, and XI are minor risk factors for VTE, while other thrombophilic disorders, such as deficiencies of protein C, protein S, or antithrombin, are major risk factors.17 The pathogenesis of VTE initially involves a small clot with partial venous occlusion. The pathway can progress down 2 pathways: the thrombus can be lysed and the endothelium repaired resulting in recovery; or, if the processes of hypercoagulability, venous stasis and endothelial damage continue, the thrombus may enlarge, causing complete vascular occlusion. Partial vessel occlusion is often painful, with erythema and edema of the affected limb. Complete venous occlusion can block blood flow in the adjacent artery, leading to pain, cyanosis, and ultimately gangrenous necrosis. Mobilization of the thrombus to the pulmonary circulation can lead to fatal pulmonary embolism.18,19 DVT typically presents in the veins of the lower extremity, most commonly in the peroneal vein, followed by the soleal, and posterior tibial. The least commonly affected is the gastrocnemius vein, for unknown reasons.19 DVT of the proximal veins is thought to increase the risk of developing a PE.
Risk Assessment Hospitalization is among the most important risk factors for VTE because this is a unique period in which many predisposing conditions may be present (surgery, trauma, intravenous catheters, immobilization, pregnancy, chronic conditions). Rates of VTE for hospitalized surgical patients are up to 150 times higher compared with patients undergoing same-day surgery.9,11 The American College of Chest Physicians has published comprehensive guidelines regarding VTE risk stratification and thromboprophylaxis that are widely accepted and updated regularly.2,4 These guidelines stratify risk level based on a group-specific classification system assigning patients to low, moderate, or high risk of VTE (Table 1). The risk of developing a DVT is multifactorial but risk factors can be considered major or minor. Major risk factors include the following: age; type and length of surgery (with major neurosurgical or orthopedic surgery being the highest, and major vascular, gynecologic, and urologic surgery also significantly increasing risk)2,4;
Table 1. RISK FACTORS ASSOCIATED WITH VTE2,4,8,14,21,25,26,27,43,63
Major Age (⬎40 yr old) Type of surgery Prior VTE Major acute trauma Presence of malignancy Immobilization
Minor Hormone replacement therapy Oral contraceptives Vein varicosities Acute CVA Postpartum period Smoking Pregnancy Heart failure COPD Central venous catheterization Myeloproliferative disease Type of anesthesia
Williams, Indresano, and O’Ryan. Venous Thromboembolism in Oral and Maxillofacial Surgery. J Oral Maxillofac Surg 2011.
major trauma; history of VTE; presence of malignancy; and immobility. Minor risk factors include most thrombophilic disorders, pregnancy, hormone replacement therapy, oral contraceptive use, varicosities, obesity, and smoking.4,8,18 The incidence of DVT increases synergistically with the number of identified risk factors.20 Advanced age is a major risk factor with most DVT and PE occurring in elderly patients, especially those who are wheelchair or bed bound.21,22 Length and type of surgery are among the greatest risk factors; lengthy neurosurgical and orthopedic procedures involving the hip are associated with the highest incidence of postoperative DVT.9,21,23,24 Oral contraceptives or hormone replacement therapy also increase VTE risk depending on the dose, duration, and hormone type.25-27 Finally, ethnicity may play a role in DVT pathogenesis. Asians have a threefold risk of postoperative DVT, while African Americans have a slightly higher risk compared with Caucasians, and Latinos have the lowest risk.28 In the absence of prophylaxis, low-risk patients (⬍40 years old, no other risk factors, minor surgical procedure) have a 1% risk of developing DVT and 0.1% risk of developing a PE.29 Moderate-risk patients (⬎40 years old; malignancy; obesity; major gynecologic, abdominal, or urological surgery; prolonged immobilization; varicose veins) have a 10% to 40% risk of developing DVT, a 2% to 10% risk of a proximal DVT, and a 0.1% to 0.7% risk of a fatal PE.21,29 Highrisk patients have a 40% to 80% chance of distal DVT, 10% to 25% chance of a proximal DVT, and a 1% to 10% chance of a fatal PE.29
Diagnosis Although 30% to 50% of DVT are estimated to be asymptomatic, clinical signs and symptoms are the first step in making a diagnosis.30 Signs include unilateral
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lower extremity leg edema; a hard, band-like palpable vein; localized tenderness with erythema; loss of ipsilateral peripheral pulses (may be present with a large DVT); fever; malaise; and warmth adjacent to the site of pain. Homan’s sign (pain on dorsiflexion of the ankle), once considered a helpful clinical test, has low sensitivity and specificity for DVT, making it unreliable when used without other diagnostic modalities.18,31 Progression of DVT to PE may cause chest pain, dyspnea, decreased pulse oximetry reading, tachypnea, sinus tachycardia, and hemoptysis. Duplex or compression ultrasonography is the most common imaging modality used in the diagnosis of DVT with 94% specificity and 98% sensitivity for veins above the knee (ie, popliteal and femoral vessels).30,31 However, sensitivity and specificity are both slightly reduced in the iliac veins, owing to their depth, as well as the smaller more distal calf veins.31 Despite this, duplex ultrasonography is typically the first line of imaging used to diagnose a DVT and is generally reliable.32 D-dimers are degradation products of cross-linked fibrin and can be used in the diagnosis of DVT. However, unrelated conditions can cause a false-positive d-dimer test such as inflammation, pregnancy, surgery, trauma, and hemorrhage, which limits its utility as a single diagnostic modality. With a negative ddimer test, the clinician can confidently omit DVT or PE from the differential diagnosis; however, a positive d-dimer does not confirm the presence of VTE. Coupled with radiographic imaging, the d-dimer test can be useful in ruling out a PE and is therefore still commonly used.30,32 Magnetic resonance venography (MRV) and computed tomographic venography (CTV) are useful technologies for detecting DVT, especially in areas where compression ultrasonography is less accurate, such as a thrombus in the iliac veins, distal calf veins, or a suspected PE.24,30,31 MRV is expensive, may be contraindicated in some patients (eg, claustrophobia, implanted metal devices, inability to remain motionless for an extended period, hypersensitivity or allergy to intravenous contrast agents), and requires injection of gadolinium. CTV requires injection of a radioactive contrast agent, and timing the injection with the actual scan to capture images of the target veins can be technically difficult. Sensitivities and specificities for both approach 100%, making each a very useful diagnostic tool for detecting DVT and PE.24,30,31 Pulmonary angiography is the gold standard diagnostic test; however, it is rarely used owing to the potential serious complications.14,30,31 For these reasons, MRV and CTV, if available, are typically the diagnostic tools of choice.
Thromboprophylaxis A variety of prophylactic mechanical and pharmacologic measures have been used to reduce VTE risk. Mechanical compression devices include graded elastic compression stockings, intermittent pneumatic compression devices, and foot pumps. Pneumatic compression devices apply intermittent, sequential pressure to the calves, thighs, or feet by means of disposable sleeves connected to a pump via plastic hoses. Increased venous blood flow and stimulation of fibrinolytic mediators are thought to be the mechanisms of action.4,21,33-35 When used as monotherapy, mechanical compression devices can reduce the incidence of DVT up to 66%.36-38 However, there is no reliable evidence that shows mechanical prophylaxis is effective in preventing death from VTE.21 Pharmacologic therapy, in the form of intravenous heparin, or more recently oral anticoagulants, has been the primary modality of thromboprophylaxis for the past 35 years. Unfractionated heparin with vitamin K antagonists have largely been replaced with low-molecular weight heparin (LMWH), owing to the ease of use and safer application of LMWH compared with unfractionated heparin.36-38 Studies of newer oral anticoagulants in patients undergoing orthopedic surgery have shown similar efficacy when compared with LMWH.39-41 Rivaroxaban, an oral factor Xa inhibitor, and dabigan, an oral thrombin inhibitor, have the advantages of avoiding daily injections and international normalized ratio monitoring with the potential for greater patient compliance in the postdischarge period.42 Stainless steel or titanium inferior vena cava filters may be indicated in adequately anticoagulated patients with DVT, in patients with thromboembolic disease who are contraindicated for anticoagulation, or in patients with high risk for PE. The Greenfield filter, first introduced in 1974, still serves as the standard against which other filters are judged.
Incidence in Oral and Maxillofacial Surgery and Other Head and Neck Specialties Limited data exist about VTE risk in patients undergoing oral and maxillofacial surgery; however, available studies have shown that VTE risk is exceptionally low with an estimated range of 0.15% to 1.6%.43-46 Two postal surveys conducted in the UK found a low incidence of VTE, with malignancy or trauma as the primary risk factors in those patients who experienced thrombotic events.18 Only 67% of the oral maxillofacial surgeons polled in one of these surveys admitted to routinely implementing DVT prophylaxis. Few studies have investigated the incidence of VTE in patients without malignancies undergoing orthog-
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nathic and various types of reconstructive maxillofacial procedures. Van de Perre et al described 3 cases of VTE (2 DVT and 1 PE) in a series of 2049 patients (0.15%) monitored during hospitalization.44 Blackburn et al reported 2 cases of symptomatic DVT in 129 consecutive orthognathic surgery patients (1.6%) monitored for 3 months after surgery. Both patients underwent bimaxillary surgery: one patient had an iliac graft and the other was taking oral contraceptives.45 In a retrospective series of 411 patients (none received DVT prophylaxis) undergoing orthognathic and preprosthetic surgery, Forouzanfar et al reported 2 patients (0.5%) who developed nonfatal PEs. Both patients were obese and surgery included iliac grafts and postoperative immobility.46 One patient developed a PE the first week after hospital discharge, while the other was diagnosed 1 day postoperatively. However, because follow-up information was obtained via telephone interviews, the incidence of VTE may have been underreported in this cohort. Individuals with obstructive sleep apnea (OSA) pose a particular concern because they are predisposed to hypercoagulability, demonstrating high levels of fibrinogen, decreased fibrinolysis, and enhanced platelet activity.47-53 The severity of OSA has been correlated with increased platelet aggregation, which normalizes in response to continuous positive airway pressure (CPAP).53 The mechanism by which OSA increases VTE risk is likely multifactorial involving obesity (body mass index ⬎30) and hyperlipidemia, among other factors. Because mechanoprophylaxis may not be effective in obese patients, chemoprophylaxis should be considered.21 Infection has been considered a risk factor for VTE.54 Although it is not known whether patients with complex multispace maxillofacial infections are at greater risk for VTE, a protracted hospital course, which may include admission to the intensive care unit, prolonged immobilization, central venous catheterization, mechanical ventilation, sedation, and neuromuscular blocking agents, are all associated with increased risk of VTE.55-57 Data regarding thromboembolic events in related surgical subspecialties have showed a low incidence of VTE, in the range of 0.1% to 0.6% with greater incidence in patients with malignancies.4,58,59 A postal survey of 273 plastic surgeons performing nearly 10,000 rhytidectomy procedures found the incidence of VTE to be 0.49%.60 Systematic reviews of VTE-related articles reported in head and neck surgical subspecialties (plastic surgery, otolaryngology, and oral and maxillofacial surgery) have concluded that there are inadequate data to institute a standardized prophylaxis protocol.61,62 Additionally, because VTE frequently occurs within the first 3 months after surgery, it is important to
ascertain the risk factor profile and actual incidence of postdischarge VTE.64-69 In conclusion, the incidence of VTE in hospitalized patients undergoing oral and maxillofacial surgery is low. However, because of the expanding surgical scope and treatment of medically complex patients, further research regarding the incidence and risk factors for VTE in the contemporary oral and maxillofacial surgery population is needed.
References 1. Heit JA, Cohen AT, Anderson FA Jr, et al: Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood 10:910, 2005 2. Geerts WH, Pinco GF, Heit JA, et al: Prevention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126:338, 2004 3. Zhan C, Miller MR: Excess length of stay, charges and mortality attributable to medical injuries during hospitalization. JAMA 290:1868, 2003 4. Geerts WH, Berqvist D, Pineo GF, et al: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 133:318, 2008 5. Wood K: A history of pulmonary embolism and deep venous thrombosis. Crit Care Clin 25:115, 2009 6. Prevention of fatal postoperative pulmonary embolism by low doses of heparin: An international multicentre trial. Lancet 2:45, 1975 7. Virchow R: Gesammalte Abhandlungen Zur Wissenschaftlichen. Frankfurt, Germany, Medinger Sohn & Co, 1856 8. Coleridge-Smith PD, Hasty JH, Scurr JH: Venous stasis and vein lumen changes during surgery. Br J Surg 77:1055, 1990 9. Jaffer AK, Brotman DJ: Prevention of venous thromboembolism after surgery. Clin Geriatr Med 24:625, 2008 10. Kim V, Spandorfer J: Epidemiology of venous thromboembolic disease. Emerg Med Clin North Am 19:839, 2001 11. Kyrle PA, Eichinger S: Deep vein thrombosis. Lancet 365:1163, 2005 12. Coleridge-Smith PD, Hasty JH, Scurr JH: Deep vein thrombosis: Effect of graduated compression stockings on distension of the deep veins of the calf. Br J Surg 78:724, 1991 13. Comerota AJ, Stewart GJ, Alburger PD, et al: Operative venodilation: A previously unsuspected factor in the cause of postoperative deep vein thrombosis. Surgery 106:301, 1989 14. Merli GJ: Pathophysiology of venous thrombosis and the diagnosis of deep vein thrombosis---Pulmonary embolism in the elderly. Cardiol Clin 26:203, 2008 15. Merli GJ: Pathophysiology of venous thrombosis, thrombophilia, and the diagnosis of deep vein thrombosis: Pulmonary embolism in the elderly. Clin Geriatr Med 22:75, 2006 16. Laffan M: Genetics and pulmonary medicine: Pulmonary embolism. Thorax 53:698, 1998 17. Friedman T, Michaels VJ, Bontempo F, et al: Hereditary coagulopathies: Practical diagnosis and management for the plastic surgeon. Plast Reconstr Surg 125:1544, 2010 18. Lowry JC: Thromboembolic disease and thromboprophylaxis in oral and maxillofacial surgery: Experience and practice. Br J Oral Maxillofac Surg 33:101, 1995 19. Labropoulos N, Kang SS, Mansour MA, et al: Early thrombus remodelling of isolated calf deep vein thrombosis. Eur J Vasc Endovasc 23:344, 2002 20. Caprini JA: Risk assessment as a guide for the prevention of the many faces of venous thromboembolism. Am J Surg 199:3, 2010 21. Kaboli P, Henderson MC, White RH: DVT prophylaxis and anticoagulation in the surgical patient. Med Clin North Am 87:77, 2003 22. Hirsh J, Hoak J: Management of deep vein thrombosis and pulmonary embolism: A statement for healthcare professionals. Circulation 93:2212, 1996
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23. Kakkar AK, Cohen AT, Tapson VF, et al: Venous thromboembolism risk and prophylaxis in the acute care hospital setting (ENDORSE survey): Findings in surgical patients. Ann Surg 251:330, 2010 24. Wells PS, Anderson DR, Bormanis J, et al: Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 350:1795, 1997 25. Farmer RD, Lawrenson RA, Thompson CR, et al: Populationbased study of risk of venous thromboembolism associated with various oral contraceptives. Lancet 349:83, 1997 26. Lidegaard Ø, Løkkegaard E, Svendsen AL, et al: Hormonal contraception and risk of venous thromboembolism: National follow-up study. BMJ 339:2890, 2009 27. Douketis JD, Julian JA, Kearon C, et al: Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study. J Thromb Haemost 3:943, 2005 28. White RH, Zhou H, Romano PS: Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med 128:737, 1998 29. Hull R, Raskob G, Hirsch J: Prophylaxis of venous thromboembolism: An overview. Chest 89(5 Suppl 1):S374, 1986 30. Beyer J, Schellong S: Deep vein thrombosis: Current diagnostic strategy. Eur J Intern Med 16:238, 2005 31. Bundens WP: Diagnosis of deep vein thrombosis, in Bergan J (ed): The Vein Book. New York, Academic Press, 2006, pp 353-357 32. Tick LW, Ton E, van Voorthuizen T, et al: Practical diagnostic management of patients with clinically suspected deep vein thrombosis by clinical probability test, compression ultrasonography, and d-dimer test. Am J Med 113:630, 2002 33. Vanhoutte PM, Boulanger CM, Mombouli JV: Endotheliumderived relaxing factors and converting enzyme inhibition. Am J Cardiol 76:3E, 1995 34. Allenby F, Boardman L, Pflug JJ, et al: Effects of external pneumatic intermittent compression on fibrinolysis in man. Lancet 2:1412, 1973 35. DiGiovanni CW, Restrepo A, Sharrock NE, et al: The safety and efficacy of intraoperative heparin in total hip arthroplasty. Clin Orthop Relat Res 379:178, 2000 36. Gallus A, Raman K, Darby T: Venous thrombosis after elective hip replacement—The influence of preventive intermittent calf compression and of surgical technique. Br J Surg 70:17, 1983 37. Hills NH, Pflug J, Jeyesingh K, et al: Prevention of deep vein thrombosis in intermittent pneumatic compression of calf. BMJ 1:131, 1972 38. Fisher CG, Blachut PA, Salvian AJ, et al: Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: A prospective, randomized study of compression alone versus no prophylaxis. J Orthop Trauma 9:1, 1995 39. Selby R, Geerts W: Prevention of venous thromboembolism: Consensus, controversies, and challenges. Hematology Am Soc Hematol Educ Progr 286, 2009 40. Rosencher N, Bellamy L, Arnaout L: Should new oral anticoagulants replace low-molecular-weight heparin for thromboprophylaxis in orthopaedic surgery? Arch Cardiovasc Dis 102:327, 2009 41. Eriksson BI, Quinlan DJ, Weitz JI: Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet 48:1, 2009 42. Abrams PJ, Rivaroxaban ECR: A novel, oral, direct factor Xa inhibitor. Pharmacotherapy 29:167, 2009 43. Solomon JM, Schow SR: The potential risks, complications, and prevention of deep vein thrombosis in oral and maxillofacial surgery patients. J Oral Maxillofac Surg 53:1441, 1995 44. Van de Perre JPA, Stoelinga PJ, Blijdorp PA, et al: Perioperative morbidity in maxillofacial orthopaedic surgery: A retrospective study. J CranMaxillofac Surg 24:263, 1996 45. Blackburn TK, Pritchard K, Richardson D: Symptomatic venous thromboembolism after orthognathic operation: An audit. Br J Oral Maxillofac Surg 44:389, 2006 46. Forouzanfar T, Heymans MW, van Schuilenburg A, et al: Incidence of venous thromboembolism in oral and maxillofacial
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Venous Thromboembolism in Oral and Maxillofacial Surgery: A Review of the Literature Bryce Williams, DDS,* A. Thomas Indresano, DMD,† and Felice O’Ryan, DDS‡ Background
Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism, or a combination of both, is among the most common complication in hospitalized patients, with an estimated 900,000 cases occurring annually.1 Pulmonary embolism resulting from DVT is the leading cause of preventable hospital deaths.2 In over 7 million patients discharged from acute care hospitals in the United States, VTE was the second most common medical complication, the second most common cause of increased length of hospital stay, the third most common cause of mortality and a significant increase in financial cost.3 Although disagreement exists regarding risk classification of thromboembolism in hospitalized individuals, most of these patients have at least 1 risk factor for VTE and almost one half have 3 or more risk factors.4 With the continually expanding surgical scope and treatment of medically complex patients in the contemporary oral maxillofacial surgical practice, it is imperative to be aware of the risk factors for VTE and implement evidence-based thromboprophylaxis strategies. This article reviews classic and current literature regarding the pathophysiology, risk factors, and prophylaxis of venous thromboembolism in an effort to increase awareness of this potentially devastating complication.
Clinical signs of DVT are thought to have been first described by the Indian surgeon Susruta between 600 and 1000 BC, who observed a patient with a “swollen and painful leg, which was difficult to treat.”5 In the 18th and 19th centuries European anatomists Giovanni Battista Morgagni (1761) and later Jean Cruveilhier (1849) discovered clots in the pulmonary vasculature of cadavers that they postulated were related to an inflammatory process.5 Cruveilhier’s frequently repeated phrase, “La phlebite domine toute la pathologie” (“phlebitis dominates all of pathology”), was an expression familiar to Rudolf Virchow, a German physician studying the pathology of thrombosis.6 By 1856, Virchow had postulated the pathophysiology of thromboembolism, which was later termed “Virchow’s triad.” This triad now refers to 3 components important in thrombogenesis: venous stasis, endothelial damage, and hypercoagulability.7 Several risk factors in surgical patients, either acquired or inherent, may increase the probability of occurrence of any or all of the components of Virchow’s triad.
Pathophysiology Venous stasis, aggravated by immobilization, is among the most important risk factors for thrombotic events in hospitalized patients. Stagnation of venous blood creates local hypoxia, which directly activates clotting factors, particularly factor X.8 In the surgical patient, intraoperative venous dilation and distension, due to the effects of anesthesia, are thought to be additional factors contributing to venous stasis.9-13 Endothelial damage, which activates both intrinsic and extrinsic coagulation pathways, may be the result of direct (trauma or surgery) or indirect injury (sepsis, vasculitis, chemotherapy).14 Vascular wall injury causes release of coagulation factors and exposure of underlying collagen, which in turn induces platelet adhesion and subsequent aggregation.9,11 Acute vessel trauma reduces endothelial cell production of tissue plasminogen activator, further contributing to thrombus formation.15 Tissue factor (CF VII), also stimulated by endothelial damage, triggers the extrinsic coagulation pathway.
*Resident, Department of Oral and Maxillofacial Surgery, University of the Pacific/Highland Hospital, Oakland, CA. †Director, Department of Oral and Maxillofacial Surgery, University of the Pacific/Highland Hospital, Oakland, CA. ‡Division of Maxillofacial Surgery, Kaiser Permanente, Oakland Medical Center, Oakland, CA. Address correspondence and reprint requests to Dr O’Ryan: Kaiser Permanente Division of Maxillofacial Surgery, 280 West MacArthur Blvd, Oakland, CA 94611; e-mail: Felice.O’[email protected] © 2011 American Association of Oral and Maxillofacial Surgeons
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The third feature of Virchow’s triad, hypercoagulability, is related to a number of genetic and acquired characteristics; with heritable coagulopathies, malignancies, oral contraceptives, or hormone replacement therapy being the more common predisposing factors.4,5,10 The factor V Leiden gene, the most common hereditary thrombophilia, occurs in 5% to 15% of the general population, and the homozygous form increases the risk of DVT sixfold.16 Other congenital thrombophilic disorders, including prothrombin G20210A, and elevated levels of factors VII, IX, and XI are minor risk factors for VTE, while other thrombophilic disorders, such as deficiencies of protein C, protein S, or antithrombin, are major risk factors.17 The pathogenesis of VTE initially involves a small clot with partial venous occlusion. The pathway can progress down 2 pathways: the thrombus can be lysed and the endothelium repaired resulting in recovery; or, if the processes of hypercoagulability, venous stasis and endothelial damage continue, the thrombus may enlarge, causing complete vascular occlusion. Partial vessel occlusion is often painful, with erythema and edema of the affected limb. Complete venous occlusion can block blood flow in the adjacent artery, leading to pain, cyanosis, and ultimately gangrenous necrosis. Mobilization of the thrombus to the pulmonary circulation can lead to fatal pulmonary embolism.18,19 DVT typically presents in the veins of the lower extremity, most commonly in the peroneal vein, followed by the soleal, and posterior tibial. The least commonly affected is the gastrocnemius vein, for unknown reasons.19 DVT of the proximal veins is thought to increase the risk of developing a PE.
Risk Assessment Hospitalization is among the most important risk factors for VTE because this is a unique period in which many predisposing conditions may be present (surgery, trauma, intravenous catheters, immobilization, pregnancy, chronic conditions). Rates of VTE for hospitalized surgical patients are up to 150 times higher compared with patients undergoing same-day surgery.9,11 The American College of Chest Physicians has published comprehensive guidelines regarding VTE risk stratification and thromboprophylaxis that are widely accepted and updated regularly.2,4 These guidelines stratify risk level based on a group-specific classification system assigning patients to low, moderate, or high risk of VTE (Table 1). The risk of developing a DVT is multifactorial but risk factors can be considered major or minor. Major risk factors include the following: age; type and length of surgery (with major neurosurgical or orthopedic surgery being the highest, and major vascular, gynecologic, and urologic surgery also significantly increasing risk)2,4;
Table 1. RISK FACTORS ASSOCIATED WITH VTE2,4,8,14,21,25,26,27,43,63
Major Age (⬎40 yr old) Type of surgery Prior VTE Major acute trauma Presence of malignancy Immobilization
Minor Hormone replacement therapy Oral contraceptives Vein varicosities Acute CVA Postpartum period Smoking Pregnancy Heart failure COPD Central venous catheterization Myeloproliferative disease Type of anesthesia
Williams, Indresano, and O’Ryan. Venous Thromboembolism in Oral and Maxillofacial Surgery. J Oral Maxillofac Surg 2011.
major trauma; history of VTE; presence of malignancy; and immobility. Minor risk factors include most thrombophilic disorders, pregnancy, hormone replacement therapy, oral contraceptive use, varicosities, obesity, and smoking.4,8,18 The incidence of DVT increases synergistically with the number of identified risk factors.20 Advanced age is a major risk factor with most DVT and PE occurring in elderly patients, especially those who are wheelchair or bed bound.21,22 Length and type of surgery are among the greatest risk factors; lengthy neurosurgical and orthopedic procedures involving the hip are associated with the highest incidence of postoperative DVT.9,21,23,24 Oral contraceptives or hormone replacement therapy also increase VTE risk depending on the dose, duration, and hormone type.25-27 Finally, ethnicity may play a role in DVT pathogenesis. Asians have a threefold risk of postoperative DVT, while African Americans have a slightly higher risk compared with Caucasians, and Latinos have the lowest risk.28 In the absence of prophylaxis, low-risk patients (⬍40 years old, no other risk factors, minor surgical procedure) have a 1% risk of developing DVT and 0.1% risk of developing a PE.29 Moderate-risk patients (⬎40 years old; malignancy; obesity; major gynecologic, abdominal, or urological surgery; prolonged immobilization; varicose veins) have a 10% to 40% risk of developing DVT, a 2% to 10% risk of a proximal DVT, and a 0.1% to 0.7% risk of a fatal PE.21,29 Highrisk patients have a 40% to 80% chance of distal DVT, 10% to 25% chance of a proximal DVT, and a 1% to 10% chance of a fatal PE.29
Diagnosis Although 30% to 50% of DVT are estimated to be asymptomatic, clinical signs and symptoms are the first step in making a diagnosis.30 Signs include unilateral
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lower extremity leg edema; a hard, band-like palpable vein; localized tenderness with erythema; loss of ipsilateral peripheral pulses (may be present with a large DVT); fever; malaise; and warmth adjacent to the site of pain. Homan’s sign (pain on dorsiflexion of the ankle), once considered a helpful clinical test, has low sensitivity and specificity for DVT, making it unreliable when used without other diagnostic modalities.18,31 Progression of DVT to PE may cause chest pain, dyspnea, decreased pulse oximetry reading, tachypnea, sinus tachycardia, and hemoptysis. Duplex or compression ultrasonography is the most common imaging modality used in the diagnosis of DVT with 94% specificity and 98% sensitivity for veins above the knee (ie, popliteal and femoral vessels).30,31 However, sensitivity and specificity are both slightly reduced in the iliac veins, owing to their depth, as well as the smaller more distal calf veins.31 Despite this, duplex ultrasonography is typically the first line of imaging used to diagnose a DVT and is generally reliable.32 D-dimers are degradation products of cross-linked fibrin and can be used in the diagnosis of DVT. However, unrelated conditions can cause a false-positive d-dimer test such as inflammation, pregnancy, surgery, trauma, and hemorrhage, which limits its utility as a single diagnostic modality. With a negative ddimer test, the clinician can confidently omit DVT or PE from the differential diagnosis; however, a positive d-dimer does not confirm the presence of VTE. Coupled with radiographic imaging, the d-dimer test can be useful in ruling out a PE and is therefore still commonly used.30,32 Magnetic resonance venography (MRV) and computed tomographic venography (CTV) are useful technologies for detecting DVT, especially in areas where compression ultrasonography is less accurate, such as a thrombus in the iliac veins, distal calf veins, or a suspected PE.24,30,31 MRV is expensive, may be contraindicated in some patients (eg, claustrophobia, implanted metal devices, inability to remain motionless for an extended period, hypersensitivity or allergy to intravenous contrast agents), and requires injection of gadolinium. CTV requires injection of a radioactive contrast agent, and timing the injection with the actual scan to capture images of the target veins can be technically difficult. Sensitivities and specificities for both approach 100%, making each a very useful diagnostic tool for detecting DVT and PE.24,30,31 Pulmonary angiography is the gold standard diagnostic test; however, it is rarely used owing to the potential serious complications.14,30,31 For these reasons, MRV and CTV, if available, are typically the diagnostic tools of choice.
Thromboprophylaxis A variety of prophylactic mechanical and pharmacologic measures have been used to reduce VTE risk. Mechanical compression devices include graded elastic compression stockings, intermittent pneumatic compression devices, and foot pumps. Pneumatic compression devices apply intermittent, sequential pressure to the calves, thighs, or feet by means of disposable sleeves connected to a pump via plastic hoses. Increased venous blood flow and stimulation of fibrinolytic mediators are thought to be the mechanisms of action.4,21,33-35 When used as monotherapy, mechanical compression devices can reduce the incidence of DVT up to 66%.36-38 However, there is no reliable evidence that shows mechanical prophylaxis is effective in preventing death from VTE.21 Pharmacologic therapy, in the form of intravenous heparin, or more recently oral anticoagulants, has been the primary modality of thromboprophylaxis for the past 35 years. Unfractionated heparin with vitamin K antagonists have largely been replaced with low-molecular weight heparin (LMWH), owing to the ease of use and safer application of LMWH compared with unfractionated heparin.36-38 Studies of newer oral anticoagulants in patients undergoing orthopedic surgery have shown similar efficacy when compared with LMWH.39-41 Rivaroxaban, an oral factor Xa inhibitor, and dabigan, an oral thrombin inhibitor, have the advantages of avoiding daily injections and international normalized ratio monitoring with the potential for greater patient compliance in the postdischarge period.42 Stainless steel or titanium inferior vena cava filters may be indicated in adequately anticoagulated patients with DVT, in patients with thromboembolic disease who are contraindicated for anticoagulation, or in patients with high risk for PE. The Greenfield filter, first introduced in 1974, still serves as the standard against which other filters are judged.
Incidence in Oral and Maxillofacial Surgery and Other Head and Neck Specialties Limited data exist about VTE risk in patients undergoing oral and maxillofacial surgery; however, available studies have shown that VTE risk is exceptionally low with an estimated range of 0.15% to 1.6%.43-46 Two postal surveys conducted in the UK found a low incidence of VTE, with malignancy or trauma as the primary risk factors in those patients who experienced thrombotic events.18 Only 67% of the oral maxillofacial surgeons polled in one of these surveys admitted to routinely implementing DVT prophylaxis. Few studies have investigated the incidence of VTE in patients without malignancies undergoing orthog-
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nathic and various types of reconstructive maxillofacial procedures. Van de Perre et al described 3 cases of VTE (2 DVT and 1 PE) in a series of 2049 patients (0.15%) monitored during hospitalization.44 Blackburn et al reported 2 cases of symptomatic DVT in 129 consecutive orthognathic surgery patients (1.6%) monitored for 3 months after surgery. Both patients underwent bimaxillary surgery: one patient had an iliac graft and the other was taking oral contraceptives.45 In a retrospective series of 411 patients (none received DVT prophylaxis) undergoing orthognathic and preprosthetic surgery, Forouzanfar et al reported 2 patients (0.5%) who developed nonfatal PEs. Both patients were obese and surgery included iliac grafts and postoperative immobility.46 One patient developed a PE the first week after hospital discharge, while the other was diagnosed 1 day postoperatively. However, because follow-up information was obtained via telephone interviews, the incidence of VTE may have been underreported in this cohort. Individuals with obstructive sleep apnea (OSA) pose a particular concern because they are predisposed to hypercoagulability, demonstrating high levels of fibrinogen, decreased fibrinolysis, and enhanced platelet activity.47-53 The severity of OSA has been correlated with increased platelet aggregation, which normalizes in response to continuous positive airway pressure (CPAP).53 The mechanism by which OSA increases VTE risk is likely multifactorial involving obesity (body mass index ⬎30) and hyperlipidemia, among other factors. Because mechanoprophylaxis may not be effective in obese patients, chemoprophylaxis should be considered.21 Infection has been considered a risk factor for VTE.54 Although it is not known whether patients with complex multispace maxillofacial infections are at greater risk for VTE, a protracted hospital course, which may include admission to the intensive care unit, prolonged immobilization, central venous catheterization, mechanical ventilation, sedation, and neuromuscular blocking agents, are all associated with increased risk of VTE.55-57 Data regarding thromboembolic events in related surgical subspecialties have showed a low incidence of VTE, in the range of 0.1% to 0.6% with greater incidence in patients with malignancies.4,58,59 A postal survey of 273 plastic surgeons performing nearly 10,000 rhytidectomy procedures found the incidence of VTE to be 0.49%.60 Systematic reviews of VTE-related articles reported in head and neck surgical subspecialties (plastic surgery, otolaryngology, and oral and maxillofacial surgery) have concluded that there are inadequate data to institute a standardized prophylaxis protocol.61,62 Additionally, because VTE frequently occurs within the first 3 months after surgery, it is important to
ascertain the risk factor profile and actual incidence of postdischarge VTE.64-69 In conclusion, the incidence of VTE in hospitalized patients undergoing oral and maxillofacial surgery is low. However, because of the expanding surgical scope and treatment of medically complex patients, further research regarding the incidence and risk factors for VTE in the contemporary oral and maxillofacial surgery population is needed.
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