Thank you. Learning Objectives. Deep Venous Thrombosis Protocols In Podiatric Surgery. FPMA January 11, Robert G. Smith DPM, MSc, R.Ph., C.

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1 Deep Venous Thrombosis Protocols In Podiatric Surgery Robert G. Smith DPM, MSc, R.Ph., C.Ped FPMA January 11, 2018 Thank you Learning Objectives Recognize the potential for venous thromboembolic disease in foot and ankle surgery. List the known patients risk factors for development for venous thromboembolic disease as reported in the medical literature Recognize and understand both chemical and mechanical modalities for venous thromboembolic disease prophylaxis available for patients undergoing for and ankle surgery. 1

2 Deep Venous Thrombosis Prophylaxis in Podiatry Literature There is currently insufficient data to recommend for or against routine VTED prophylaxis for patients undergoing foot and ankle surgery. We do recommend, however, that patients be assessed preoperatively for VTED risk. If sufficient risk factors are present, VTED prophylaxis may be considered and weighed against the potential risks of prophylaxis. Acceptable options for prophylaxis include mechanical and chemical agents. (AOFAS Board of Directors Position Statement, July 9, 2013) The routine use of venous thromboembolism prophylaxis in patients undergoing foot and ankle procedures is not well supported in the literature. Multiple studies draw conclusions from heterogeneous populations, and specific studies have small numbers of specific pathologic conditions. Depending on the study, recommendations for and against venous thromboembolism prophylaxis in foot and ankle surgery can be made. The identification of risk factors for venous thromboembolism is paramount in the decision making of postoperative venous thromboembolism prophylaxis. (Chao J, Orthop Clin North Am 2016) Venous Thromboembolic Disease 3 rd most common cause of cardiovascular morbidity and mortality Proximal DVT accounts for ~80% Typical treatment: anticoagulation therapy and compression stockings Proximal DVT Distal DVT Enden, T et al. Lancet. 2012;379: Bashir R, et al. JAMA Intern Med. 2014;174(9): Image: S.Standring, ed. Overview of veins of the lower limb. In: Grays Anatomy, 39 th ed, 2005, figure 110.5, page 1403, Elsevier Ltd. 5 DVT Epidemiology and Etiology Annual incidence of venous thromboembolism (VTE) is 1/1000 DVT accounts for one half of VTE Carefully evaluated, up to 80% of patients with VTE have one or more risk factors Majority of lower extremity DVT arise from calf veins but ~20% begin in proximal veins About 20% of calf-limited DVTs will propagate proximally 2

3 Virchow s Triad Hypercoagulability Factor V Leiden Hyperhomocystein emia Protein C/S def Antithrombin def Malignancy Estrogen therapy Pregnancy Endothelial injury Stasis of blood flow Atrial fibrillation Left ventricular dysfunction Bed rest Paralysis Venous obstruction Atherosclerosis Vascular injury/trauma Abnormal or mechanical heart valve Indwelling vascular catheter DVT VTE Risk Factors Malignancy Surgery Trauma Pregnancy Oral contraceptives or hormonal therapy Immobilization Inherited thrombophillia Presence of venous catheter Congestive failure Antiphospholipid antibody syndrome Hyperviscosity Nephrotic syndrome Inflammatory bowel disease 3

4 Incidence of DVT ( Saragas et al, 2014) Two hundred and sixteen patients were included in the study. A variety of operative procedures was carried out with the common denominator being a below knee cast for at least 4 weeks and nonweightbearing for an average of 6 weeks in 130 patients. The remainder of the patients (88) had hallux surgery not requiring a cast and were allowed to weightbear. No patient received any form of thromboprophylaxis postoperatively. There was a 5.09% incidence of VTE (0.9% pulmonary embolism) overall. As no VTE (neither DVT nor pulmonary embolus) developed in the hallux subgroup, i.e. patients not requiring immobilization and were allowed to weightbear, the incidence of VTE in the cast/non-weightbearing group was 8.46%. The average timing to the diagnosis of VTE in this current study was 33.1 days. In view of the unacceptable incidence of VTE and the average total risk factor score of 5 or more (for which thromboprophylaxis is recommended) in the majority of the patients, the authors feel that the routine use of thromboprophylaxis in foot and ankle surgery requiring nonweightbearing in combination with short leg cast immobilization, is warranted. This prophylaxis should continue until the patient regains adequate mobility either by weightbearing (in or out of the cast) or removal of cast immobilization (weightbearing or nonweightbearing), usually between 28 and 42 days. ACFAS ( Fleischer et al, 2015) The purpose of this consensus statement is to provide guidance for physicians regarding the risk, prevention, and diagnosis of venous thromboembolism disease after foot and ankle surgery and while caring for lower extremity injuries that require ankle immobilization. A panel composed of all authors of this document reviewed the published evidence and, through a series of meetings, reached consensus regarding the viewpoints contained herein. We conclude that routine chemical prophylaxis is not warranted; rather, patients should be stratified and have a prevention plan tailored to their individual risk level. An effective venous thromboembolism prevention program is typically multimodal and focuses on addressing any modifiable risk factors, use of mechanical prophylaxis, early mobilization, and careful consideration of the use of chemical prophylaxis. The final decision regarding use and method(s) of prophylaxis adopted should be agreed upon by both the clinician and patient after a discussion of the potential benefits and harms as they relate to the individual. This should take place preferably during the preoperative visit or in the immediate post-injury setting, and it may need to be revisited during the course of care if the patient's risk level changes. (Well s Criteria) Evidence ( Mangwani et al, 2015) A systematic review of the published English literature on VTE prophylaxis in foot and ankle surgery using MEDLINE, EMBASE, CINHAL, Cochrane Library, without date restrictions up to December From 988 citations, 25 papers fulfilled the inclusion criteria. Conclusions were drawn on the incidence (symptomatic and asymptomatic VTE), location (distal vs. proximal), associated risk factors, timing of VTE, role of mechanical and pharmacological prophylaxis and cost effectiveness of the treatment. This review showed that the overall incidence of symptomatic VTE in foot and ankle surgery is low (0-0.55%). There is increased incidence in foot and ankle trauma patients with the highest incidence reported in tendo-achilles surgery. The reported risk factors include previous history of VTE, immobilisation, high BMI, age, co morbidities, contraceptive pill, and air-travel. There is a cumulative effect resulting in higher risk when two or more risk factors are present. 4

5 Current Practice ( Shah et al, 2015) When contemplating thromboprophylaxis for patients undergoing elective foot and ankle surgery the potential for complications secondary to venous thromboembolism (VTE) must be balanced against the cost, risk, and effectiveness of prophylactic treatment. An -based survey of active AOFAS (American Orthopaedic Foot and Ankle Society) committee members was conducted (n = 100). Surgeons were questioned as to their use, type, and duration of thromboprophylaxis following elective ankle fusion surgery. Scenarios included the following: (1) A 50-year-old woman with no risk factors; (2) a 50-year-old woman with a history of PE; and (3) a 35-year-old woman actively using birth control pills The response rate for the survey was 80% (80/100). Replies regarding the use of thromboprophylaxis were as follows: (1) in the absence of risk factors, 57% of respondents (45/80) answered, "No prophylaxis required"; (2) for the scenario in which the patient had experienced a previous PE, 97.5% of respondents (78/80) answered, "Yes" to prophylaxis use; (3) for the scenario in which the patient was on BCP, 61.3% of respondents (49/80) stated that they would give some type of thromboprophylaxis. The most commonly recommended methods of prophylaxis were aspirin, 49% (24/49), and low-molecular-weight heparin, 47% (23/49). The recommended length of time for thromboprophylaxis varied widely, from 1 day to more than 6 weeks. There remains wide variation in the practice of deep-vein thrombosis thromboprophylaxis within the foot and ankle community. Because risks for foot and ankle patients differ from those in the well-studied areas of hip and knee, specific guidelines are needed for foot and ankle surgery. Risk Factors for Extension of Distal DVT Positive D-dimer Extensive thrombus >5cm long, involves multiple veins, >7mm diameter Thrombus close to proximal veins No reversible provoking factor Active cancer History of VTE Inpatient status DVT Wells Score The following were assigned a point value of 1 if present: Cancer Paralysis or plaster immobilization Bd Bedrest t>3d or surgery in past 4 wks Localized tenderness Entire leg swollen Calf > 3cm larger than unaffected leg Pitting edema greater than unaffected leg Collateral superficial veins Alternative diagnosis more likely than DVT = 2 points Probability High ( 3), Moderate (1 2) or Low (0 or less) DVT risk: High 75%, Moderate 17%, Low 3% Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:

6 Variety of Mechanical and Chemical VTED Prophylaxis The Heart of Pharmacologic or Chemical Strategies Pharmacologic Strategies 6

7 Literature Review Centered on LMWH Clinical Base Literature Low Molecular Weight Heparins Dosing Overview Platelet-active Drugs Platelet-active drugs such aspirin or cyclooxygenase (COX-1) Inhibitors have been used to prevent thrombosis. Aspirin is effective as a platelet inhibitor at very low dosages. The Seventh ACCP Conference did not recommend the use of aspirin alone as a prophylactic agent for any patient group, because aspirin is less effective than other options, 7

8 Warfarin Kinetics Absorption Distribution Metabolism Excretion Half-life Oral: Rapid, complete 0.14 L/kg Hepatic, primarily via CYP2C9; minor pathways include CYP2C8, 2C18, 2C19, 1A2, and 3A4 Urine (92%, primarily as metabolites) hours Warfarin Onset of action: 5-7 days May requiring bridging Antidote: Vitamin K, FFP, PRBC Interactions: Foods with high vitamin K content Warfarin Medications Amiodarone Antiplatelets Azole antifungals (fluconazole) 2 nd /3 rd- gen Cephalosporins Fluoroquinolones (ciprofloxacin) Griseofulvin Isoniazid Macrolides (clarithromycin) Metronidazole NSAIDs Penicillins (nafcillin) Prednisone Rifampin SSRIs Sulfonamides (Bactrim) Tetracyclines (Doxycycline ) Herbals Ginger Gingko Fenugreek Chamomile St. John s Wort 8

9 Warfarin ADRs Bleeding/Hemorrhage/Hematuria Vasculitis Dermatitis, pruritus, urticaria Abdominal pain, N/V/D Anemia Skin necrosis, gangrene, purple toes syndrome Direct Oral Anticoagulants vs. Warfarin In patient with VTE and no cancer: Dabigatran, rivaroxaban, apixaban, or edoxaban over Vitamin K Antagonist Lower risk of bleeding Comparable recurrent VTE risk reduction 2010 Pradaxa 2011 Xarelto 2012 CHEST 9 th ed 2012 Eliquis 2014 Edoxaban Key changes in the 2016 VTE Update DOACs are suggested over warfarin for initial and long-term treatment of VTE in patients without cancer Routine use of compression stockings is no longer recommended to prevent postthrombotic syndrome Subsegmental pulmonary embolism Who should/should not receive therapy 9

10 Rivaroxaban MOA: selective/reversible direct inhibitor of factor Xa Prevents the conversion of prothrombin to thrombin Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin Rivaroxaban Creatine Clearance (ml/min) > <15 or HD Atrial fibrillation 20 mg po daily 15 mg po daily Avoid use Postoperative thromboprophylaxis Treatment of PE/VTE Secondary Prophaxis for PE/VTE 10 mg 10 mg po Avoid use Avoid use daily, use with caution po daily Knee: days Hip: 35 days 15 mg twice daily x21 days, then 20 mg po daily Use with caution 20 mg po daily Use with caution Avoid use Avoid use Avoid use Avoid use Rivaroxaban Monitoring Prothrombin time (PT) CBC with differential Renal/hepatic function Onset: 2-4 hours Antidote: None 10

11 Rivaroxaban ADRs Pruritus (2%) Bleeding DVT prophylaxis: 6% [major: <1%] Atrial fibrillation: 21% [major: 6%] Thrombocytopenia (3%) Increase in liver enzymes (7%-3%) Rivaroxaban ISMP Medication Safety Alert: 10/4/2012 Primary event: Thrombus 158 cases, 44.4% of the total Hemorrhage 121 cases, 34% of the total Apixaban MOA: oral direct Xa inhibitor Dose: 5mg twice daily Dose: 5mg twice daily Dose reduction to 2.5mg twice daily if 2+ of the following: Age 80 years Body weight 60kg Scr 1.5mg/dl AVOID in CrCl <15 ml/min 11

12 Apixaban Kinetics Absorption Distribution Metabolism Rapid; Intestines V d: 21 L 15% liver metabolism CYP3A4/5 P-gp Excretion Primarily Biliary/Fecal (46-56%) Renal (27%) unchanged Half-life 8 to 15 hours Apixaban Monitoring Minimal impact on the PT, INR, or aptt Factor Xa inhibition Onset: 3-4 hours Antidote: None Contraindications to DOACs Extreme BMI (>40) CrCl <30 Significant increased risk of bleeding 12

13 VTE and Patients without Cancer Use Direct Oral Anticogulates preferred! Rivaroxaban, apixaban No bridging needed Dbi Dabigatran, edoxaban Start with parenteral anticoagulation x5 days If contraindications to DOAC, then use Vitamin K Anticoagulant therapy (warfarin) Overlap with parenteral anticoagulation x5 days, And INR >2 for 24 hours Risk Factors for Bleeding on Anticoagulant Therapy Age >65 Age >75 Previous bleeding Cancer Mt Metastatic tti cancer Renal failure Liver failure Thrombocytopenia Previous stroke Low risk Moderate risk High risk Diabetes Anemia Antiplatelet therapy Poor anticoagulant control Comorbidity and reduced dfunctional capacity Recent surgery Frequent falls Alcohol abuse NSAID use 0 risk factors 1 risk factor 2 risk factors 13

14 Duration of Therapy Proximal DVT or PE Isolated Distal DVT Cancerassociated Upper extremity DVT Provoked 3 months (Grade 1B) Low bleeding risk Unprovoked Mod bleeding risk High bleeding risk Mild symptoms or high bleeding risk Severe symptoms or risk for extension Extended therapy (Grade 1B) Anticoagulate (Grade 2C) Extended therapy (first VTE - Grade 2B, second VTE - Grade 1B) Extended therapy (first VTE - Grade 2B, second VTE - Grade 2B) 3 months (first VTE - Grade 1B, second VTE - Grade 2B) Serial imaging x2 weeks (Grade 2C) Extending thrombus Anticoagulate (Grade 2C) Anticoagulate (Grade 1B, 2C) Preferred Agents Factor Preferred anticoagulant Notes Cancer LMWH Want to avoid parenteral therapy Rivaroxaban; apixaban VKA, edoxaban, dabigatran require initial parenteral anticoagulation Once daily therapy preferred Rivaroxaban; edoxaban; VKA Liver disease with coagulopathy LMWH DOACs CI if INR raised due to liver disease CrCl <30 ml/min VKA DOACs and LMWH CO with severe renal impairment CAD VKA; rivaroxaban; apixaban; edoxaban ACS more often with dabigatran than with VKA Hx GI bleeding; dyspepsia VKA; apixaban Dabigatran had high incidence of dyspepsia and GIB; rivaroxban and edoxaban may be associated with higher rate of GIB compared to VKA References Chao J. Deep Vein Thrombosis in Foot and Ankle Surgery. Orthop Clin North Am Apr;47(2): Shah K et al; Deep-vein thrombosis prophylaxis in foot and ankle surgery: what is the current state of practice? Foot Ankle Spec Apr;8(2): Saragas NP et al. The impact of risk assessment on the implementation of venous thromboembolism prophylaxis in foot and ankle surgery.foot Ankle Surg Jun;20(2):

15 References Smith RG Low-Molecular-Weigh Heparins: A Overview for the Podiatric Physician Journal of the American Podiatric Medical Association (4) Schade VL, Roukis TS Antithrombotic pharmacologic prophylaxis use during conservative and surgical management of ffoot and ankle disorders: d a systematic ti review. Clin Podiatr Med Surg Jun;28(3): Fleischer AF, et al American College of Foot and Ankle Surgeons' clinical consensus statement: risk, prevention, and diagnosis of venous thromboembolism disease in foot and ankle surgery and injuries requiring immobilization. J Foot Ankle Surg 2015 May-June; 54 (3): References Mangwani J, et al. What is the evidence for chemical thromboprophylaxis in foot and ankle surgery? Systematic review of the English literature. Foot 2015 Sep;25(3): Rivaroxaban FDA Monograph Apixaban FDA Monograph Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350: Conclusions There remains wide variation in the practice of deep-vein thrombosis thromboprophylaxis within the foot and ankle community. Because risks for foot and ankle patients differ from those in the well-studied areas of hip and knee, specific guidelines are needed for foot and ankle surgery. Depending on the study, recommendations for and against venous thromboembolism prophylaxis in foot and ankle surgery can be made. The identification of risk factors for venous thromboembolism is paramount in the decision making of postoperative venous thromboembolism prophylaxis. ASAMAAN@cfl.rr.com 15

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