Pertinent Pointers On DVT Prophylaxis

The incorporation of an evidence-based approach in modern medicine is in line with Einstein’s comment that “The important thing is not to stop questioning.” The evolution of evidence-based medicine requires curiosity and a hunger for knowledge. Often, searching for answers only raises more questions and this is certainly the case with deep vein thrombosis (DVT). Research in the area of DVT has resulted in a wealth of knowledge in the medical and general surgical arenas. Unfortunately, little has been written about DVT within the podiatric literature. Orthopedic writings on DVT prophylaxis focus extensively on hip and knee arthroplasty since researchers reported that total hip and knee arthroplasty (THA and TKA) patients have a 70 percent risk of developing DVT postoperatively.1 In regard to DVT, there are some key questions to answer. • What is the cause of a DVT in the perioperative patient? • What is the incidence of DVTs in the foot and ankle patient? • What does the literature say in regard to the timing of initiating prophylaxis? In addition to understanding the current guidelines as they relate to the orthopedic population, clinicians should also be aware of risk stratification schemes. Understanding The Potential Impact Of DVT Deep vein thrombosis is a major complication that can occur after surgical intervention and several possible sequelae may result.2 The patient may experience chronic pain, swelling, skin ulceration secondary to post-phlebitic syndrome and pulmonary embolism (PE). Every year, an estimated one in 1,000 people in the general population will experience DVT and the risk increases proportionally with patient age. Every year, 500,000 cases of DVT and PE occur with a preponderance of the PEs (70 percent) being diagnosed post-mortem.3 Likewise, approximately 70 percent of patients symptomatic from a concurrent PE are dead within the first hour of symptom onset.1 Researchers say the use of appropriate thromboprophylaxis could prevent approximately 20,000 to 30,000 deaths in the United States alone.4 As one can see, the magnitude of these sequelae ranges from localized lower extremity symptoms to a life-threatening event. What Causes DVT In The Perioperative Patient? The exact sequence leading to DVT formation is unknown. In 1859, Virchow derived his famous triad regarding DVT formation and he observed the following causes: blood stasis, changes in vessel wall continuity and hypercoagulability.5 In the operative setting, a DVT may result from venous stasis, an acquired hypercoagulable state with inhibition of the fibrinolytic system, endothelial injury, limb position and tourniquet use.1 In the presence of endothelial injury, subendothelial ligands become exposed and eventually activation of integrins occurs. The clotting cascade continues and results in clot formation.5 Stasis of blood is what most commonly precipitates venous thrombosis.6,7 The incidence of DVT in hospitalized patients falls as patients begin to walk, supporting the idea that immobility and stasis precipitate DVT.5,8 Blood stasis has also been linked to endothelial damage. Evidence indicates that stasis can result in hemoglobin desaturation, leading to a hypoxic insult to the endothelium.9 Since the endothelium is primarily oxygenated and perfused directly by the blood in the vessel lumen, hypoxia can result in various cellular responses depending on the degree and duration of the hypoxia. This ischemia activates endothelial cells and a protein linked to leukocyte infiltration, inflammation and thrombosis in thrombophlebitis.5,10 It is a common belief that tourniquets cause stasis or vessel injury, and result in an increased risk of DVT formation. However, in an age-matched venography study examining the operative side with tourniquet, the operative side without tourniquet and control legs without tourniquet and operation, DVTs were similarly present in the operative extremities with and without tourniquets.11 In fact, the control group had a higher DVT incidence. Researchers have found that DVTs occur in 17 to 54 percent of patients examined with tourniquet use during surgery.12 In contrast, other authors found a lower occurrence of DVTs in the tourniquet group (10 percent) versus a non-tourniquet group (30 percent).13 Some have suggested that tourniquet use may provide a protective effect in surgery with tourniquet release providing a thrombolytic therapy. The fibrinolytic cascade undergoes a “shutdown” for 48 hours to several days following surgery.14 Tourniquet use combats this fibrinolytic collapse and prevents clot formation. This effect maximizes at 15 minutes after tourniquet deflation and returns to preoperative levels after an additional 15 minutes.11 Perioperative immobilization may also result in thrombi formation. Several anticoagulant studies show a reduced incidence of DVT with the use of low-molecular weight heparin (LMWH).15-17 One such study found a reduction of DVT incidence from 16.5 percent to 4.8 percent with the use of LMWH in patients immobilized in lower extremity casts.17 Study authors recommended prophylaxis for all patients immobilized in a plaster cast for lower extremity injuries irrespective of age and other risk factors such as smoking, obesity, contraception and history of thrombosis.17 Researchers believe the use of regional or spinal anesthesia in DVT high-risk surgery reduces thrombus formation risk in comparison with general anesthesia.18 Regional or spinal anesthesia provides a sympathetic blockade, leading to vasodilatation of the lower limbs and increased blood flow, which facilitates less blood stasis.19 Regional anesthesia also inhibits platelet coagulation and alters coagulative and fibrinolytic responses to further prevent clotting. In contrast, other authors believe general anesthesia completely inhibits fibrinolytic function and leads to an increased formation of thrombi.20 Many studies have shown that regional anesthesia is associated with a lower incidence of DVT when no thromboprophylaxis is given.19,21,22 What About The Incidence Of Post-Op DVT In The Lower Extremity? The incidence of DVT after foot and ankle surgery has not been studied extensively. The limited number of studies cite a DVT incidence of 0.22 percent to 4 percent.23-26 Obviously, this incidence will depend on individual risk factors (see “Risk Factors For DVT In Patients Who Undergo Orthopedic Surgery” above). It is important to realize thromboembolic risk factors have a cumulative effect on the overall level of risk.4 Due to the significance of the relationship between risk presence and DVT occurrence, some risk categorization schemes have been established for orthopedic surgical patients. For a guide to one of these risk categorization schemes, see “THRIFT-II Guidelines On DVT Risk Classification” below).4,27,28 What The Literature Reveals About Medications For DVT Prophylaxis Many medications are available for use in prophylaxis regimens. These medications include enoxaparin sodium injection, unfractionated heparin (UFH), warfarin sodium tablets, etc. McGarry and colleagues compared enoxaparin sodium injection to UFH in immobilized medical inpatients and found a 74 percent lower risk of DVT development with enoxaparin therapy.29 Michot, et. al., observed that dalteparin lowered the incidence of DVT in patients after outpatient arthroscopic knee surgery.29,30 Leclerc, et. al., also found reduced DVT occurrence from 65 percent with placebo to 19 percent with enoxaparin use (p<0.0001).31 Similarly, Levine, et. al., reported a reduction in DVTs with 30 percent in the ardeparin group and 59 percent in the placebo group (p < 0.001).32,33 Finally, in a study comparing enoxaparin to warfarin in patients undergoing TKAs, researchers found no statistical difference in the DVT rate between the treatment groups.34 Overall, studies have shown the effectiveness of various medications. Intermittent pneumatic compression (IPC) is also available. This device acts as a mechanical pump that combats lower extremity blood stasis while promoting the clearance of activated coagulation factors. More importantly, a local fibrinolytic effect counteracts the hypercoagulable state imposed by surgery.35,36 In a comparison study of thigh-length IPC to warfarin therapy, warfarin was more effective. In a similarly designed study, the incidence of DVT was 17 percent in both the warfarin and IPC groups.35,37 When should prophylaxis begin? The findings of fibrinolytic collapse, vessel damage and blood stasis perioperatively lead some individuals to believe that DVTs form during surgery. Some have observed increased arterial levels of fibrinopeptide A, thrombin–antithrombin complexes, D-dimer, tissue plasminogen activator (t-PA) activity and t-PA antigen upon tourniquet deflation.38 Other clinicians also believe the clot forms during surgery, especially after interpretation of their study findings using serial ascending venograms.39 Subsequently, authors recommended preoperative prophylaxis.40 Providing pre-op prophylaxis does not appear to increase surgical bleeding.40,41 A systematic review of 33 randomized controlled trials in which researchers began prophylactic medications from two to 24 hours prior to surgery showed injection site bruising as the most common complication in 6.9 percent of the patients. This was followed by wound hematoma in 5.7 percent of the patients and the need for subsequent operations for bleeding issues in 0.7 percent of patients.42 Additional studies with intraoperative heparin have shown comparable blood loss to a control group and low DVT incidence.43 What You Should Know About The Antithrombotic Prophylaxis Guidelines While there are guidelines for DVT prophylaxis for the surgical patient, these guidelines are devoid of specific recommendations for the foot and ankle surgeon. Muntz described the Methodist Hospital Deep Vein Thrombosis Prophylaxis Risk Factor Assessment system. This system gives a point score to the patient based on age, DVT history, the presence of other comorbidities including protein C or S deficiency, the length of general anesthesia time, etc. This score categorizes the patients as low risk, moderate risk, high risk or very high risk. One would utilize pharmacologic and non-pharmacologic therapies based on the risk stratification. For example, a moderate risk patient will receive low dose UFH every eight to 12 hours or ICD +/- elastic stockings. In contrast, a very high risk patient will receive LMWH, oral anticoagulation with target INR 2.0-3.0 or SCD plus heparin (LMWH or low-dose unfractionated heparin (LDUFH)).1 Perhaps the most important guidelines on DVT prophylaxis emerged from the Sixth ACCP Consensus Conference on Antithrombotic Therapy (see “A Guide To VTE Risk And Key Prevention Strategies” below). These guidelines provide the most comprehensive evidence-based guidelines for the prevention of venous thromboembolism (VTE) in surgical patients.44 According to the guidelines, nonpharmacologic interventions include early ambulation, elastic stockings, IPC devices and inferior vena caval filters. Pharmacologic methods include aspirin, UFH, warfarin, LMWH and synthetic pentasaccharides. According to the guidelines, in most patients, it is appropriate to initiate VTE prophylaxis as soon as the risk of developing thrombosis begins. For trauma patients, this means as soon as they are hospitalized. For elective surgery patients, it is as soon as they are taken to the operating room. For recently immobilized patients, it may be prior to hospital admission. One should initiate stockings and IPC devices preoperatively as soon as the risk of immobility increases and then continue them during the procedure and throughout the hospital stay. One may initiate warfarin at a low dose 10 to 14 days preoperatively or at a therapeutic dose on the night prior to surgery. For LMWH, the optimal timing to maximize efficacy and minimize bleeding is not yet clear. Options include initiating LMWH 12 hours preoperatively, immediately prior to surgery, as soon as hemostasis is achieved after surgery or 12 to 24 hours postoperatively. Relative contraindications for DVT prophylaxis use include: a previous history of cerebral hemorrhage; intestinal bleed or stroke within the past six months; thrombocytopenia, coagulopathy, active intracranial lesions/ neoplasms; proliferative retinopathy; and vascular access/biopsy sites inaccessible to hemostatic control. Absolute contraindications to prophylaxis are: active hemorrhage from wounds, drains, lesions; heparin use in heparin-induced thrombocytopenia and thrombosis; warfarin use in pregnancy; and severe trauma to head, spinal cord or extremities with hemorrhage within four weeks.1 One may consider aspirin therapy if LMWH is contraindicated.7 In Conclusion The original aim of this article was to provide concrete guidelines as to what patients may require DVT prophylaxis, when clinicians should begin therapy and whether there is an established range of DVT incidence following foot and ankle surgery. Quite honestly, due to the paucity of evidence presented in foot and ankle publications, one cannot establish a definitive guideline at this point. However, we do have the benefit of examining the current orthopedic guidelines. Unfortunately, they are based on surgical procedures about the knee and hip where the incidence of DVT is approximately 60 to 70 percent, thereby necessitating these patients be placed on preventative therapy. If the overall DVT incidence after foot and ankle surgery is in fact lower than that of more proximal orthopedic procedures, then we would need to see revision of the risk stratification schemes to be of more relevance for podiatric surgeons. The development of guidelines and a modified risk stratification for podiatric surgical patients are desperately needed. Since there is no consensus opinion on DVT prophylaxis for foot and ankle surgeons, the following pearls are based upon findings in the orthopedic literature and are merely suggestions. • A team approach is necessary when dealing with the long-term orally anticoagulated patient. • If the patient possesses any of the risk factors and will be immobilized, anticoagulation before, during, or after the procedure would be beneficial. • More studies are needed, but the length and type of operation may influence the need for prophylaxis. Larger procedures such as triple arthrodesis or cavus foot reconstruction as well as those procedures lasting longer than two hours may benefit from anticoagulation. • Choosing regional anesthesia whenever possible will lower that patient’s risk of developing a DVT. n Dr. Ponticello is a second-year resident at INOVA Fairfax Hospital Podiatric Residency Program in Falls Church, Va. Dr. Steinberg is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. References 1. Muntz JE. Deep vein thrombosis and pulmonary embolism in the perioperative patient. American Journal of Managed Care, 2000. 6(20(S)): p. 1045-1052. 2. Scarvelis D. Diagnosis and treatment of deep-vein thrombosis. CMAJ, Oct 24 2006. 175(9): p. 1087-1092. 3. Arcelus JI, RJ, Caprini JA. Finding the right fit: effective thrombosis risk stratification in orthopedic patients. Orthopedics, 2000. 23(6(S)): p. 633-638. 4. Arcelus JI, Kudrna JC, Caprini JA. Venous Thromboembolism following major orthopedic surgery: What is the risk after discharge? Orthopedics, 2006. 29(6): p. 506-516. 5. López JA, Kearon C, Lee AY. Deep Venous Thrombosis. American Society of Hematology, 2004: p. 439-456. 6. Gibbs N. Venous thrombosis of the lower limbs with particular reference to bed rest. Br J Surg, 1957. 45. 7. Sameer B, Kurup H, Gul A, Andrew JG. Thromboprophylaxis following cast immobilisation for lower limb injuries–—survey of current practice in United Kingdom. Injury, 2006. 37: p. 813-817. 8. Turpie AG, Gallus A, Beattie WS, Hirsh J, Prevention of venous thrombosis in patients with intracranial disease by intermittent pneumatic compression of the calf. Neurology, 1977. 27: p. 435-438. 9. Hamer JD, Malone PC, Silver IA. The PO2 in venous valve pockets: its possible bearing on thrombogenesis. Br J Surg, 1981. 68:166-170. 10. Kanwar S, Smith CW, Kubes P. An absolute requirement for P-selectin in ischemia/reperfusion-induced leukocyte recruitment in cremaster muscle. Microcirculation, 1998. 5: p. 281-287. 11. Angus P, Nakielny R, Goodrum DT. The pneumatic tourniquet and deep venous thrombosis. JBJS, 1983. 65B(3): p. 336-339. 12. Cohen SH, Ehrlich GE, Kauffman MS, Cope C, Thrombophlebitis following knee surgery. JBJS, 1973. 55A: p. 106-112. 13. Fahmy NR. Hemostatic changes and postoperative deep-vein thrombosis associated with use of a pneumatic tourniquet. JBJS, 1981. 63A: p. 461-465. 14. Knight MT, Dawson R, Melrose DG. Fibrinolytic response to surgery: labile and stable patterns and their relevance to postoperative deep venous thrombosis. Lancet, 1977. 2: p. 370-373. 15. Leizorovicz A, Haugh MC, Chapuis FR, et al. Low molecular weight heparin in prevention of perioperative thrombosis. BMJ, 1992. 305: p. 913-920. 16. Lassen MR, Borris LC, Nakov RL. Use of the low-molecularweight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization. New Engl J Med, 2002. 347(10): p. 726-730. 17. Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb. Hemostasis, 1993. 23(1(S)): p. 20-26. 18. Cook TM, Baylis RJ, Marjot R. Prophylaxis of venous thromboembolism. Regional anaesthesia reduces thromboembolic morbidity. BMJ, 1997. 314:1282-1283. 19. Davis FM, Quince M, Laurenson VG, Deep vein thrombosis and anesthetic technique in emergency hip surgery. BMJ, 1980. 281: p. 1528-1529. 20. Prins MH, Hirsh J. A comparison of general anesthesia and regional anesthesia as a risk factor for deep vein thrombosis following hip surgery: a critical review. Thromb. Hemost., 1990. 64: p. 497-500. 21. Edmonds MJR, Crichton TJH, Runciman WB, Pradhan M. Evidence-based risk factors for postoperative deep vein thrombosis. Anz J Surg, 2004. 74: p. 1082-1097. 22. Thorburn J, Louden JR, Vallance R. Spinal and general anesthesia in total hip replacement: frequency of deep vein thrombosis. Br J Anesthesia, 1980. 52: p. 1117-1121. 23. Cirlincione AS, Mendicino R, Catanzariti R, Grossman J. Low-Molecular-Weight Heparin for Deep Vein Thrombosis Prophylaxis in Foot and Ankle Surgery: A Review. JFAS, 2001. 40(2): p. 96-100. 24. Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle. FAI, 2002. 23(5): p. 411-414. 25. Hanslow S, Grujic L, Slater HK, Chen D. Thromboembolic disease after foot and ankle surgery. FAI, 2006. 27(9): p. 693-695. 26. Mizel M, Temple HT, Michelson JD, et. al. Thromboembolism after foot and ankle surgery. Clin Ortho Rel Res, 1998. 348: p. 180-185. 27. Scurr J, et. al. Risk of and prophylaxis for venous thromboembolism in hospital patients. Phlebology, 1998. 13: 87-97. 28. Nicolaides AN, Breddin HK, Fareed J, et. al. Prevention of venous thromboembolism. International Consensus Statement. Int Angiology, 2001. 20: p. 1-37. 29. McGarry LJ, Stokes M, Thompson D. Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients. Thrombosis Journal, 2006. 4(17): p. 1-9. 30. Michot M, Conen D, Holtz D, et. al. Prevention of Deep-Vein Thrombosis in Ambulatory Arthroscopic Knee Surgery: A Randomized Trial of Prophylaxis With Low–Molecular Weight Heparin. Arthroscopy, 2002. 18(3): p. 257-263. 31. Leclerc JR, Geerts WH, Desjardins L, et. al. Prevention of deep vein thrombosis after major knee surgery—a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Hemostasis, 1992. 67: p. 417-423. 32. Colwell CW, Hardwick ME. Rationale for Low-molecular-weight Heparin Prophylaxis after Total Knee Arthroplasty. Clin Ortho Rel Res, 2006. 452: 181-185. 33. Levine MN, Gent M, Hirsh J, et. al. Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism: a randomized trial in patients undergoing knee surgery. Arch Int Med, 1996. 156: p. 851-856. 34. Stern SH, Wixson RL, O’Connor D. Evaluation of the Safety and Efficacy of Enoxaparin and Warfarin for Prevention of Deep Vein Thrombosis After Total Knee Arthroplasty. J Arthroplasty, 2000. 15(2): p. 153-158. 35. Kaempffle F, Lifeso RM, Meinking C. Intermittent Pneumatic Compression Versus Coumadin Prevention of Deep Vein Thrombosis in Lower-Extremity Total Joint Arthroplasty. Clin Ortho Rel Res, 1991. 269: p. 89-97. 36. Allenby B, Pflug JJ, Boardman L, Calnan JS. Effects of external pneumatic compression on fibrinolysis in man. Lancet, 1973. 2. 37. Paiement G, Wessinger SJ, Waltman AC, Hams WH. Low-dose warfarin versus external pneumatic compression for prophylaxis against venous thromboembolism following total hip replacement. J Arthroplasty, 1987. 2. 38. Sharrock NE, Go G, Sculco TP. Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. J Arthroplasty, 1995. 10. 39. Maynard MJ, S.T., Ghelman B. Progression and regression of deep vein thrombosis after total knee arthroplasty. Clin Ortho Rel Res, 1991. 273. 40. Kaboli P, Henderson MC, White RH. DVT prophylaxis and anticoagulation in the surgical patient. Med Clin N Am, 2003. 87: p. 77-110. 41. Heit J. 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CE Exam #151 Choose the single best answer to the following questions. 1. Possible sequelae of deep vein thrombosis (DVT) include: a) chronic pain b) skin ulceration secondary to post-phlebitic syndrome c) pulmonary embolism (PE) d) All of the above 2. Which of the following sentences about DVT and pulmonary embolism (PE) are true? a) Every year, 500,000 cases of DVT and PE occur with a preponderance of PE (70 percent) being diagnosed post-mortem. b) Every year, 200,000 cases of DVT and PE occur with one-third of PE being diagnosed post-mortem. c) Every year, 200,000 cases of DVT and PE occur with a preponderance of PE (70 percent) being diagnosed post-mortem. d) None of the above 3. The incidence of DVT among hospitalized patients … a) decreases as patients begin to walk b) is primarily related to the misuse of tourniquets c) is strongly correlated with the level of endothelial damage d) None of the above 4. Which of the following statements is false in regard to the use of regional anesthesia? a) When surgeons use regional anesthesia in DVT high-risk surgery, it reduces thrombus formation risk in comparison with general anesthesia. b) It inhibits platelet coagulation and decreases vasodilation of the lower limbs. c) Many studies have shown that regional anesthesia is associated with a lower incidence of DVT when no thromboprophylaxis is given. d) None of the above. 5. In comparing enoxaparin sodium injection to unfractionated heparin in immobilized medical inpatients, McGarry and colleagues found that the enoxaparin treatment group had a __ percent lower risk of DVT. a) 32 b) 74 c) 56 d) 10 6. In a systematic review of 33 randomized controlled trials in which researchers began prophylaxis medications from two to 24 hours prior to surgery, what was the most common complication? a) Wound hematoma b) The need for additional operations to address bleeding issues c) Injection site bruising d) None of the above 7. According to guidelines from the Sixth ACCP Consensus Conference on Antithrombotic Therapy, one should initiate venous thromboembolism (VTE) prophylaxis for trauma patients … a) two to three hours after hospital admission b) as soon as they are taken to the operating room c) as soon as they are hospitalized d) None of the above 8. According to the THRIFT-II Guidelines on DVT risk classification, patients younger than 40 who are having major surgery greater than 30 minutes in duration but have no other risk factors are considered to be at ________ for developing DVT. a) high risk b) low risk c) moderate risk d) None of the above 9. According to guidelines from the Sixth ACCP Consensus Conference on Antithrombotic Therapy, successful VTE prevention strategies for high-risk patients include … a) low-dose unfractionated heparin (LDUFH) every 12 hours b) fondaparinux c) LDUFH every eight hours d) None of the above Instructions for Submitting Exams Fill out the enclosed card that appears on the following page or fax the form to the NACCME at (610) 560-0502. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.