Peripheral Vascular Disease/Deep Vein Thrombosis

1. Peripheral Vascular Disease/Deep Vein Thrombosis Presented By: Susanne Lester-Bennett & Julie Dillenbeck-Juers

2. Definition of Problem • Peripheral Vascular Disease (PVD): • Two distinct types of PVD (arterial, and venous). • Both involve the blood vessels of the lower extremities. Dunphy, Winland-Brown, Porter, & Thomas (2011) Mosby’s Dictionary of Medicine, Nursing, & Health Professions (2006) Reed, J. (2009)

3. Two Types of PVD • ARTERIAL--Arteriosclerosis of the arteries impedes circulation from the heart to the lower extremities, causing ischemia of the muscles in the lower extremities; also known as peripheral artery disease (PAD). • VENOUS--Valve weakening, venous stasis, venous clot formation, chronic venous insufficiency, & deep vein thromboembolism are the major types of venous PVD. There are different degrees of PVD and they are characterized by a variety of signs and symptoms. Dunphy, Winland-Brown, Porter, & Thomas (2011) Mosby’s Dictionary of Medicine, Nursing, & Health Professions (2006) Reed, J. (2009)

4. Etiology • PVD: • Atherosclerosis is the most common cause of arterial stenoses. • DVT: • Abnormalities of coagulation, endothelial injury, and/or venous stasis contribute to DVT’s. Domino, F. (2013)

5. Incidence • Prevalence is estimated to be between 8 to 12 million. • Many are asymptomatic and therefore are not diagnosed with this disease. • In a study done (Reed, J.) from 1999-2004 in men & women aged 40-69 and 70+, results showed women 40-69 were 1.8 times more likely than men to have PAD, diabetics were 3.1 more likely than non-diabetics, and hypertensive patients were 3.1 times more likely than those with blood pressures of <140/90 to have PAD. Similar patterns were identified in those 70 or older. • DVT: 100/100,000 per year; higher incidence among Caucasians and African Americans. • PVD: 1-2.7/1,000 per year Chesbro, Carter, Martinez, & Evans (2011) Domino, F. (2013)

6. Differential Diagnosis • PVD: • Phlebitis, polycythemia, anemia, Raynaud’s disease, Buerger’s disease, aneurysms, or peripheral neuropathy. • DVT: • Cellulitis, lymphedema, muscle strain/tear, fracture, compression of vein, compartment syndrome, localized allergic reaction, fatigue, or filariasis (A disease caused by filarial worms in body tissues; tend to infest the lymph nodes). Domino, F. (2013)

7. Pathophysiology of Arterial PVD Primarily characterized by narrowing of the arteries caused by atherosclerosis. Metabolic demand during exertion fails to be met when arterial stenoses causes inadequate blood flow in distal limbs. During ambulation/exercise muscle pain occurs due to ischemia and lack of arterial blood flow. Claudication (extremity pain) results when acidic products of anaerobic metabolism build up within the muscle. As disease worsens, arterial circulation diminishes, and pain worsens with minimal activity. Chesbro, Carter, Martinez, & Evans (2011) Domino, F. (2013) Dunphy, Winland-Brown, Porter, & Thomas (2011)

8. Risk Factors of PVD Smoking Inactivity Hypertension Hypercholesterolemia Diabetes mellitus Coagulation abnormalities Abdominal/pelvic surgery Estrogen/oral contraceptives Pregnancy Heart disease Race/ethnicity Education Depression Alcohol Sedentary Occupation Elevated BMI/obesity Decreased kidney function Age Brach, Solomon, Naydeck, Sutton-Tyrrell, Enright, Jenny, Chaves, & Newman ( 2008) Reed, J. (2009)

9. Screening for Arterial PVD • Resting ankle-brachial index (ABI) • most commonly used test in screening for the detection of PAD in the clinical setting. • It is calculated as the systolic blood pressure obtained at the ankle divided by the systolic blood pressure obtained at the brachial artery while the patient is lying down (Moyer, V., 2013). • An ABI score of less than 0.90 is indicative of PVD. Moyer, V. , M. D. ( 2013)

10. Clinical Findings for Arterial PVD • Subjective: • Intermittent leg pain in both calves that increases in severity with ambulation, lasts for minutes, and resolves within 10 minutes of walking cessation, mobility loss, and functional decline. • Objective: • Delayed wound healing, thick toenails, purple/black color on lower legs and ankles, dependent edema, varicose veins, dry skin, peripheral pulses may be decreased or absent, thin skin, leg ulcers, affected extremity may be cool, pale, hairless, & smaller in size; An ABI less than 0.90. McDermott, Ferrucci, Liu, Guralnik, Tian, Liao, & Cruqui (2010)

11. Management/Treatment Guidelines (Pharmacological/Non-Pharmacological) • Treatment aimed at improving blood flow or lessening cause of impaired circulation. • Usually involves education and lifestyle changes. • Minimize or eliminate risk factors. • PAD • Aggressively manage hypertension, diabetes. • Encourage walking 30 min 4 x per week. • Any ulcers/trauma will need immediate care. • Keep legs in a dependent position to encourage circulation. • No tight stockings or socks, meticulous foot care. • Aspirin daily Dunphy, L., Winland-Brown, J. Porter, B., Thomas, D. (2011)

12. Management/Treatment Guidelines (Pharmacological/Non-pharmacological) • Clopidergrel- inhibits platelet aggregation • Cilostazol- vasodilation and inhibits platelet aggregation; should not be used with heart failure. • Angioplasty may be an option for select patients. • Watch for signs of progressive ischemia (increased pain, pallor or pain at rest) • F/U every 3 months. DVT • Inpatientor outpatient (if no comorbidities) • If inpatient treat aggressively with IV unfractionated heparin or SQ low molecular weight heparin. • Initiate warfarin after patient has been on heparin therapy for 1-5 days. (5-10 mg p.o. daily until PT/INR is therapeutic [2-3]). • If not a candidate for anticoagulant therapy then vena cava filter to prevent clot migration. Esherick, J., Clark, D., Slater, E. (2013) Dunphy, L., Winland-Brown, J. Porter, B., Thomas, D. (2011)

13. PVD/DVT Social/Environmental Considerations Controlling hypertension Controlling diabetes Exercise Healthy diet Increased activity: such as walking, swimming, etc. Smoking cessation Weight loss Brach, Solomon, Naydeck, Sutton-Tyrrell, Enright, Jenny, Chaves, & Newman (2008)

14. DVT Definition of Problem, cont… • Deep vein thrombosis (DVT): • Disorder involving a thrombus (blood clot) in one of the deep veins of the body (pelvis or extremities). • An aggregation of fibrin, clotting factors, platelets, and cellular elements of blood attach to the interior wall of a vein or artery occluding the lumen of the vessel. • The iliac or femoral vein are most commonly affected. • DVT’s can embolize (travel), propagate (expands), or lyses (breaks down) spontaneously. • Pulmonary embolism results when a clot breaks away from the vessel wall and lodges in the lung, making this situation potentially life threatening. Mosby’s Dictionary of Medicine, Nursing, & Health Professions (2006)

15. DVT Risk Factors • DVT: • Critically ill patients in ICU (immobility/prolonged sedentary position) • venous insufficiency • post-stroke • trauma • indwelling intravenous catheters • oral contraceptives or hormone replacement therapy • implantation of permanent pacemaker • implantable cardioverter-defibrillator • pelvic or acetabular fractures • cancer • inherited coagulation abnormalities • Advanced heart disease Lee, Zierler, & Zierler (2012)

16. Clinical Findings for DVT • Subjective: • May be asymptomatic especially initially. May have pain. • Objective: • Warmth, erythema, tenderness, swelling of effected limb. • Possible swelling without limb tenderness. • Thrombosed vein-may feel a palpated “cord” over the effected vein. • Positive Homan’s sign-maybe?-this has a low sensitivity/low specificity. Hollier, A., Hensley, R. (2011)

17. DVTNew Pharmacological Treatment • Oral Factor Xa Inhibitor- • Apixaban(Eliquis)-5395 patients enrolled in randomized double blind study. It suggests that apixaban was not inferior to warfarin for treatment of venous thromboembolism and was associated with significantly less bleeding. (Agnelli, 2013). • Rivaroxaban(Xarelto)-8282 patients enrolled. Meta-analysis showed that rivaroxaban can be used as a single drug approach to DVT and or PE (Prins, et al., 2013). • Edoxaban-(Lixiana)-Randomized trial, 4921 patients with acute VTE, compared with warfarin was as effective with a lower risk of bleeding. (Buller, H., Decousus, H., 2013).

18. DVTNew Pharmacological Treatment continued… • Direct Thrombin inhibitor- • Dabigatran(Pradaxa)-Several large randomized controlled trails suggest that dabigatran is as efficacious as warfarin. • Randomized double blind trail, 2539 patients with acute VTE, given either dose adjusted warfarin or dabigatran, both has similar safety and efficacy, and incidence of recurrent VTE (Schulman, S. Kearon, C., Kakkar, A., et al., 2009).

19. Advantages/Disadvantages of these Agents Advantages • Fixed oral dose • Convenience • No laboratory monitoring or dose adjustments. Disadvantages • Uncontrolled bleeding/no readily available antidote. • Hemodialysis for dabigatran (Khadzhynov, D., Wagner, F. et al., 2013). • 3 or 4-factor prothrombin complexes may reverse rivaroxaban(has not been studied in humans), (Erenberg, E., Kamphuisen, P., et al., 2011).

20. DVT Non-pharmacological Treatment Compression Hose- • 30-40 mmHg of ankle pressure has mixed benefit preventing VTE; causes no harm • Should be started after anticoagulation therapy (within two weeks of diagnosis) and worn for two years (Prandoni, P., Lensing, A., et al., 2004). • Worn for two years reduce the risk of post thrombotic syndrome by 50% without increasing frequency of VTE (Brandjes, D., Buller, H., et al., 1997). Ambulation- • Ambulation is safe and should be encouraged as soon as feasible, despite concern of embolization (Kahn, S., Shrier, I., Kearon, C., 2008). • Ambulation does not increase the risk of recurrent VTE Prandoni, P., Lensing, A., et al. (2004) Brandjes, D., Buller, H., et al. (1997)

21. Questions • 1) The etiology of DVT’s consist of all but: • Abnormalities of coagulation • Endothelial injury • Venous stasis • Atherosclerosis • 2) The incidence of DVT is higher among: • Asians • Hispanics • African Americans • Amish 3) Screening for PVD is done by: • MRI • X-Ray • Pain Level • ABI

22. Questions, cont… • 4) Risk factors for PVD include: • Smoking • Hypertension • Hypercholesterolemia • All of the above • 5) Clinical findings of PAD consist of: • Continuous leg pain in both calves • Pain that lasts for hours • Pain that does not resolve with rest • An ABI less than 0.90 • 6) When treating PAD, compression stockings should be worn for: • 6 months • 12 months • 24 months • Not at all

23. Questions, cont… • 7) What is the most commonly used test to screen for PAD? A) Doppler U/S B) ABI’s C) Claudication • 8) When evaluation DVT which test is the least reliable? A) ABI’s B) Doppler U/S C) Homan’s sign D) venogram • 9) What is an effective way an effective way to remove dabigatran from the bloodstream? A) Antidote drug B) 3 or 4 Factor Prothrombin C) Hemodialysis • 10) Clinical findings of DVT include: A) erythema, warmth, pain, swelling, possible palpable cord B) erythema, warmth, no pain, swelling, possible palpable chord C) erythema, warmth, painor no pain, swelling, possible palpable chord D) None of the above

24. Answers & Rationales • 1) (D) Plaques of cholesterol, lipids, and cellular debris located in the inner layers of the walls of the arteries. This leads to narrowing and hardening of the arteries, and reduced oxygenated blood flow to the extremities (Hollier & Hensley, 2011). • 2) (C) Non-Hispanic blacks are 2.25 times more likely to have PAD than non-Hispanic whites (Mc Dermott, 2010). • 3) (D) An ankle-brachial index of less than 0.9 defines PVD. It is considered the gold-standard to screen and diagnose PVD (Hollier & Hensley, 2011). • 4) (D) Age, BMI, Alcohol consumed, diabetes, depression, less than 0.8 ABI, male, and African-American (Hollier & Hensley, 2011). 5) (D) An ABI score of less than 0.90 is indicative of PVD(Moyer, V. , M. D., 2013). • 6) (C) 30-40 mmHg of ankle pressure has mixed benefit preventing VTE; causes no harm. Should be started after anticoagulation therapy (within two weeks of diagnosis) and worn for two years (Prandoni, P., Lensing, A., et al., 2004). • 7) (B) ABI is the most commonly used test in screening for the detection of PAD in the clinical setting (Moyer, V. , M. D., 2013). • 8) (C) Homan’s sign hast low specificity and sensitivity (Hollier, A., Hensley, R., 2011) 9) (C) Hemodialysis can be used to eliminate dabigatran from the bloodstream (Khadzhynov, D., Wagner, F. et al., 2013). • 10) (C) Erythema, warmth, pain or no pain, swelling, possible palpable chord (Hollier, A., Hensley, R., 2011).

25. References Agnelli, G., Buller, H., Cohen, A., Curto, M., Gallus, A., Johnson, M., Masiukiewicz, U., Pak, R., Thompson, M., Raskob, G., Weitz, J., Oral apixaban for the treatment of acute venous thromboembolism, New England Journal of Medicine, doi: 10.1056/NEJMoa1302507 Brach, J., Solomon, C., Naydeck, B., Sutton-Tyrrell, K., Enright, P., Jenny, N., & Newman, A. (2008). Incident physical disability in people with lower extremity peripheral arterial disease: the role of cardiovascular disease. Journal of The American Geriatrics Society, 56(6), 1037-1044. doi: 10.1111/j.1532.5415.2008.01719.x Brandjes, D., Buller, H., Heijboer, H.(1997). Randomized trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet, (349), 759. Buller, H., Prins, M. (2012). Oral rivaroxaban for symptomatic venous thromboembolism, New England Journal of Medicine (366), 1287. Chesbro, S., Carter, C., Martinez, M., & Evans, G. (2011). Screening for peripheral arterial disease in a long-term care facility: considerations for clinical practice. Cardiopulmonary Physical Therapy Journal, 22(4), 36-37. Domino, F. (2013). The 5-Minute Clinical Consult 2013. (21st Ed.). Wolters Kluwer/Lippincott Williams & Wilkins: Philadelphia, PA. Dunphy, L., Winland-Brown, J., Porter, B., & Thomas, D. (2011). Primary Care: The Art and Science of Advanced Practice Nursing. (3rd Ed.). F. A. Davis Company: Philadelphia, PA. Erenberg, E., Kamphuisen, P., Sijpken, M.(2011). Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: A randomized, placebo-controlled, crossover study in healthy subject, Circulation (124), 1573. Esherick, J. S., Clark, D. S., & Slater, E. D. (2012). Current practice guidelines in primary care 2013. McGraw Hill Professional. Hollier, A., Hensley, R. (2011). Clinical guidelines in primary care, Lafayette, LA: Advanced Practice Education Associates, Inc. Khadzhynov, D., Wagner, F., Formella, S.(2013). Effective elimination of dabigatran by hemodialysis. A phase I single centre study in patients with end-stage renal disease. Journal of Thrombosis and Haemostasis, (109), 596. Lee, J., Zierier, B., & Zierier, E. (2012). The Risk Factors and Clinical Outcomes of Upper Extremity Deep Vein Thrombosis. Vascular & Endovascular Surgery, 46(2), 139-144. doi: 10.1177/1538574411432145.

26. References, cont… McDermott, M., Ferrucci, L., Liu, K., Guralnik, J., Tian, L., Liao, Y., & Criqui, M. (2010). Leg Symptom Categories and Rates of Mobility Decline in Peripheral Arterial Disease. Journal of The American Geriatrics Study, 58(7), 1256-1262. doi: 10.1111/j. 1532-5415.2010.02941.x Mosby’s Dictionary of Medicine, Nursing, & Health Professions. (2006). (7th Ed.). St. Louis, MO: Mosby. Moyer, V. (2013). Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index in adults: U.S. perventive services task force recommendation statement. Annals of Internal Medicine, 159(5), 342-348. doi: 10.7326/0003-4819-159-5-201309030-00008. Prandoni, P., Lensing, A., Prins, M. (2004). Below knee elastic compression stockings to prevent post-thrombotic syndrome: a randomized, controlled trial. Annals of Internal Medicine, (141), 249. Prins, M., Lensing, A., Bauersachs, R., van Bellan, B., Bounameaux, H., Brighton, T., Cohen, A., Davidson, B., Decousus, H., Raskob, G., Berkowitz, S., Wells, P., Thrombosis Journal, (11), 21. Reed, J. (2009). Risk factors for peripheral arterial disease in United States asymptomatic patients aged 40-69 and asymptomatic patients aged greater than or equal to 70: results from NHANES 1999-2004. Internet Journal Of Epidemiology, 7(2). Schulman, S., Kearon, C., Kakkar, A. (2009). Dabigatran versus warfarin in the treatment of acute venous thromboembolism. New England Journal of Medicine, (361) 2342. Schulman, S., Kearon, C., Kakkar, A. (2013). Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. New England Journal of Medicine, (368),709.