Dave Duddleston, MD

VP and Medical Director

Southern Farm Bureau Life

Sources of Risk for Venous Diseases� Pulmonary embolism (thrombus)

� Bleeding from anticoagulation

� Mortality from underlying disease

� Chronic wounds (venous insufficiency)

� Thrombophilias

Pulmonary Embolism� Related to Deep Vein Thrombosis (DVT)

� Lower extremities (trauma, bedrest, previous DVT)

� Pelvic veins (inflammatory disease, cancer)

� Upper extremities (intravenous access)

� Virchow’s Triad

� Stasis

� Endothelial injury

� Hypercoagulability

Why did PE occur?� Trauma

� Bedrest

� Thrombophilia

� Cancer

� Venous disease

Mortality of Pulmonary Embolism� Leiden University, The Netherlands, 2012

� 5,000 patients with first PE compared to 6,000 controls

� Followed 8 years, using a death index including cause of death

� 2x death rate in patients without malignancy, 17x death rate with malignancy

� Significant risks (cancer, CV disease) are reduced by underwriting

Figure 1. Kaplan-Meier survival curves for patients and controls.

Flinterman LE, van Hylckama Vlieg A, Cannegieter SC, Rosendaal FR (2012) Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors. PLoS Med 9(1): e1001155. doi:10.1371/journal.pmed.1001155http://127.0.0.1:8081/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001155

Recurrent Pulmonary Embolism� Increases mortality risk over time (table rating)

� The cumulative rate of late recurrence has been reported to be 8 percent at six months, 13 percent at one year, 23 percent at five years, and 30 percent at 10 years

� See also: http://williams.medicine.wisc.edu/vte_recurrence_rosendaal_2010.pdf

Figure 1. Overall cumulative recurrence rate in 929 patients with a first unprovoked VTE estimated by Kaplan-Meier analysis, with 95% CIs (dotted lines).

Sabine Eichinger et al. Circulation. 2010;121:1630-1636

Copyright © American Heart Association, Inc. All rights reserved.

Figure 3. Nomogram to compute shrunken risk scores and estimate cumulative recurrence rates of recurrent VTE by use of sex, location of VTE, and D-dimer.

Sabine Eichinger et al. Circulation. 2010;121:1630-1636

Copyright © American Heart Association, Inc. All rights reserved.

Anticoagulation� Risk from long term anticoagulation (bleeding)

� Warfarin

� Including overanticoagulation

� Direct thrombin/Factor Xa inhibitors

� Risk from underutilization of anticoagulation (where benefit would exceed risk)

Bleeding: Warfarin� Population-based cohort study of warfarin-treated

patients with atrial fibrillation: incidence of cardiovascular and bleeding outcomes. London, UK –BMJ Open

� 16,500 pts with atrial fibrillation, anticoagulated with warfarin, followed over 5 years, monitored for *hospitalization for bleeding*

� Range was 3.8-4.5 events/100 patient-years for current and recent warfarin, vs. 2.9 for non-use.

BMJ Open 2014;4:e003839. doi:10.1136/bmjopen-2013 003839

Bleeding: Direct thrombin/Xa

inhibitors� Risk of Bleeding With Dabigatran in Atrial

Fibrillation� Inmaculada Hernandez, PharmD1; Seo Hyon Baik, PhD1; Antonio Piñera, MD2;

Yuting Zhang, PhD1

� 1Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 2Department of Obstetrics and Gynecology, La Paz University Hospital, Madrid, Spain

� Risk of bleeding in this short term study was about 1.5x that of warfarin, in Medicare patients diagnosed with atrial fib and treated with either agent.

JAMA Intern Med. 2015;175(1):18-24. doi:10.1001/jamainternmed.2014.5398

Bleeding: Direct thrombin/Xa

inhibitors� Comparative risk of gastrointestinal bleeding

with dabigatran, rivaroxaban, and warfarin: population based cohort study

� BMJ 2015 http://dx.doi.org/10.1136/bmj.h1857 Published 24 April 2015

� Suggests that risk is a bit higher with warfarin in younger to middle age; Thrombin/Xa inhibitors a little riskier at older ages

Fig 2 Dabigatran versus warfarin in patients with atrial fibrillation: treatment effect by age.

Neena S Abraham et al. BMJ 2015;350:bmj.h1857

©2015 by British Medical Journal Publishing Group

Fig 3 Rivaroxaban versus warfarin patients with atrial fibrillation: treatment effect by age.

Neena S Abraham et al. BMJ 2015;350:bmj.h1857

©2015 by British Medical Journal Publishing Group

Venous Ulcers� Leg ulcers from chronic venous insufficiency are

relatively common

� Growth of wound centers

� Most ulcers can be healed

� What are the long term risks?

Death Related to Venous

Insufficiency is Uncommon� European Journal of Vascular and Endovascular Surgery

Volume 13, Issue 5, May 1997, Pages 500–508

Long-term prognosis for patients with chronic leg ulcers: a prospective cohort study

� Patients with venous ulcers had a survival not significantly different from controls and patients with arterial or other aetiologies had a doubled risk of death.

doi:10.1016/S1078-5884(97)80179-7

Venous Insufficiency: Outcome of

Ulcers� “We included 11 studies that

reported on mortality. In most of these studies, deaths were rare, occurring in less than 5 percent of patients, and did not differ between intervention groups.” (2014)

Thrombophilia� Traditional risk factors are more important in

determination of first and recurrent thrombosis, but what is the impact of a thrombophilia found at diagnosis of a venous thrombosis?

� Risk Factors for Venous Thromboembolism

� Samuel Z. Goldhaber, MD

� J Am College of Cardiology 2010;56:1–7

Thrombophilia Risk� Factor V Leiden

� Prothrombin gene mutation

� Antiphospholipid antibody syndrome (acquired)

� “Thrombophilia workups are expensive and usually add little to patient management.”

Thrombophilia Risks� More aggressive thrombophilias include:

� Anticardiolipin antibodies, homozygous factor V Leiden, homozygous prothrombin gene mutation, double heterozygote mutations, protein C, protein S, and antithrombin deficiency

A Case of VTE� Consult: “I’m back on (an Xa inhibitor) for a clot.”

� 28 YO female with DVT and PE 3 years earlier

� Oral contraceptives

� Tobacco

� Heterozygote Factor V Leiden

� Subsequently pregnant, no DVT on an injectable Xainhibitor during pregnancy

A Case of VTE� Undesired pregnancy and took the “morning after pill”

� Developed leg pain

� CT chest negative for PE

� LLE nonocclusive defect in popliteal vein, favoring a chronic finding

� Your recommendation for treatment?

� Your decision for underwriting?

A Case of VTE� Patient was seen by an expert hematologist

� Treatment was discontinued

� Would treat prophylactically during a high risk event such as pregnancy, injury, bedrest

� Her risk of another VTE?

� Her risk of death?