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Deep Venous Thrombosis Protocols In Podiatric Surgery

Robert G. Smith DPM, MSc, R.Ph., C.Ped

FPMAJanuary 11, 2018

Thank you

Learning Objectives

• Recognize the potential for venous thromboembolicdisease in foot and ankle surgery.

• List the known patients’ risk factors for development for p pvenous 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.

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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, g ( ,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)

• 3rd most common cause of cardiovascular morbidity and

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Venous Thromboembolic Disease

Proximal DVT

mortality• Proximal DVT accounts for ~80%• Typical treatment: anticoagulation

therapy and compression stockings

Image: S.Standring, ed. Overview of veins of the lower limb. In: Grays Anatomy, 39th ed, 2005, figure 110.5, page 1403, Elsevier Ltd.

Enden, T et al. Lancet. 2012;379:31-38.Bashir R, et al. JAMA Intern Med. 2014;174(9):1494-1501.

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Distal DVT

DVT – Epidemiology and Etiology

• Annual incidence of venousthromboembolism (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

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Virchow’s Triad

Stasis of blood flow

Hypercoagulability

• Factor V Leiden• Hyperhomocystein

emia• Atrial fibrillation• Left ventricular

Endothelial injury

emia• Protein C/S def• Antithrombin def• Malignancy• Estrogen therapy• Pregnancy

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

• Presence of venouscatheter

• Congestive failure• Antiphospholipid• Pregnancy

• Oral contraceptives orhormonal therapy

• Immobilization• Inherited thrombophillia

Antiphospholipidantibody syndrome

• Hyperviscosity• Nephrotic syndrome• Inflammatory bowel

disease

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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(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

h b b li i i i ll l i d l d fvenous 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 2012.

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.

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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 e-mail-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 ofDistal DVT

• Positive D-dimer• Extensive thrombus

– >5cm long, involves multiple veins, >7mmdiameter

• Thrombus close to proximal veins• No reversible provoking factor• Active cancer• History of VTE• Inpatient status

DVT – Wells Score

• Cancer• Paralysis or plaster

immobilizationB d t > 3d i

• Entire leg swollen• Calf > 3cm larger than

unaffected leg• Pitting edema greater than

The following were assigned a point value of 1 if present:

• Bedrest > 3d or surgery in past 4 wks

• Localized tenderness

• Pitting edema greater thanunaffected 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;350:1795‐8

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Variety of Mechanical and Chemical VTED Prophylaxis

The Heart of Pharmacologic or Chemical Strategies

Pharmacologic Strategies

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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 lowAspirin 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,

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WarfarinKineticsAbsorption Oral: Rapid, complete

Distribution 0.14 L/kgg

Metabolism Hepatic, primarily via CYP2C9; minor pathways include CYP2C8, 2C18, 2C19, 1A2, and 3A4

Excretion Urine (92%, primarily as metabolites)

Half-life 20-60 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)

– Prednisone– Rifampin– SSRIs– Sulfonamides (Bactrim)

Tetracyclines (Doxycycline )– 2nd/3rd-gen Cephalosporins– Fluoroquinolones (ciprofloxacin)– Griseofulvin– Isoniazid– Macrolides (clarithromycin)– Metronidazole– NSAIDs– Penicillins (nafcillin)

– Tetracyclines (Doxycycline )

• Herbals– Ginger– Gingko – Fenugreek– Chamomile– St. John’s Wort

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Warfarin

• ADRs– Bleeding/Hemorrhage/Hematuria– VasculitisVasculitis– Dermatitis, pruritus, urticaria– Abdominal pain, N/V/D– Anemia– Skin necrosis, gangrene, “purple toes”

syndrome

• In patient with VTE and no cancer:– Dabigatran, rivaroxaban, apixaban, or edoxaban

Direct Oral Anticoagulants vs. Warfarin

over Vitamin K Antagonist• Lower risk of bleeding• Comparable recurrent VTE risk reduction

2010Pradaxa

2011Xarelto

2012 CHEST 9th ed

2012Eliquis

2014Edoxaban

• DOACs are suggested over warfarin forinitial and long-term treatment of VTE inpatients without cancer

Key changes in the 2016 VTE Update

p• Routine use of compression stockings is no

longer recommended to prevent post-thrombotic syndrome

• Subsegmental pulmonary embolism– Who should/should not receive therapy

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Rivaroxaban• MOA: selective/reversible direct inhibitor of

factor Xa

– Prevents the conversion of prothrombin to thrombin

– Thrombin both activates platelets and catalyzes theconversion of fibrinogen to fibrin

RivaroxabanCreatine Clearance

(mL/min)>50 50-30 29-15

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Rivaroxaban• ADRs

– Pruritus (2%)– Bleedingg

• DVT prophylaxis: 6% [major:

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Apixaban KineticsAbsorption Rapid; Intestines

Distribution Vd: 21 Ld

Metabolism 15% liver metabolismCYP3A4/5P-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 inhibitionFactor Xa inhibition

• Onset: 3-4 hours

• Antidote: None

Contraindications to DOACs

• Extreme BMI (>40)• CrCl

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VTE and Patients without Cancer

• Use Direct Oral Anticogulates – preferred!– Rivaroxaban, apixaban

• No bridging neededD bi t d b– Dabigatran, edoxaban

• Start with parenteral anticoagulation x5 days

• If contraindications to DOAC, then useVitamin 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

M t t ti

• Diabetes• Anemia• Antiplatelet therapy• Poor anticoagulant control

C bidit d d d f ti l it• Metastatic cancer• Renal failure• Liver failure• Thrombocytopenia• Previous stroke

• Comorbidity and reduced functional capacity• Recent surgery• Frequent falls• Alcohol abuse• NSAID use

Low risk 0 risk factors

Moderate risk 1 risk factor

High risk ≥2 risk factors

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Duration of Therapy

Proximal DVT or PE

Provoked

3 months

Unprovoked

Low Mod bleedingHigh

bleeding

Isolated Distal DVT

Mild symptoms

or high bleeding

risk

Severe symptoms or risk for extension

Cancer-associated

Extended therapy(Grade 1B)

Upper extremity

DVT

Anticoagulate(Grade 2C)

(Grade 1B) bleeding risk

Extended therapy(first VTE -Grade 2B,

second VTE -Grade 1B)

bleeding risk

Extended therapy (first VTE - Grade 2B,

second VTE -Grade 2B)

bleeding risk

3 months(first VTE - Grade 1B, second VTE -

Grade 2B)

risk

Serial imaging x2 weeks

(Grade 2C)

Extending thrombus

Anticoagulate(Grade 1B, 2C)

Anticoagulate(Grade 2C)

Preferred AgentsFactor Preferred anticoagulant Notes

Cancer LMWH

Want to avoid parenteral therapy Rivaroxaban; apixaban VKA, edoxaban, dabigatranrequire 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

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References• Smith RG Low-Molecular-Weigh Heparins: A Overview

for the Podiatric Physician Journal of the American Podiatric Medical Association 2005 95 (4) 383-89.

• Schade VL, Roukis TS Antithrombotic pharmacologic prophylaxis use during conservative and surgical

t f f t d kl di d t timanagement of foot and ankle disorders: a systematic review. Clin Podiatr Med Surg. 2011 Jun;28(3):571-88.

• 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): 497-507.

References

• Mangwani J, et al. What is the evidence for chemical thromboprophylaxis in foot and ankle surgery? Systematicreview of the English literature. Foot 2015 Sep;25(3):173-8.

• Rivaroxaban FDA Monograph• Apixaban FDA Monograph• Wells PS, Andersen DR, Bormanis J et al. Lancet.

1997;350:1795‐8

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• 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

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