DISCLOSURES

SPEAKERS BUREAU: ASTRA ZENECA Phil SPEAKERS BUREAU: SANOFI ADVENTIS SPEAKERS BUREAU: PFIZER Phil SPEAKERS BUREAU: SERVIER Phil SPEAKER: BOEHRINGER Phil

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Celine Teves Aquino MD FPCP FPCC Ass Professor CIM

OBJECTIVES

To define the problem of VTE in the critical care setting

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1) To enumerate the factors that promote VTE 2) To identify the reasons why VTE diagnosis in ICU is difficult 3) To review the guidelines for VTE prophylaxis in the critically ill

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Background

VENOUS THROMBO- EMBOLISM

DEEP VENOUS THROMBOSIS

PULMONARY EMBOLISM

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Acquired risk factors Age > 40 Varicose Veins Direct Trauma to Vein Immobilization Pregnancy and

Hormones Malignancy

ANY “ACTIVATION” OF VIRCHOW’S TRIAD (endothelial injury, hypercoagulability, stasis)

Hereditary factors Coagulation Disorders Female Gender

VENOUS THROMBOSIS

WHO ARE AT RISK?

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STASIS / VESSEL INJURY

•POST-OPERATIVE especially ORTHOPEDIC

SEVERE MEDICAL ILLNESS particularly SEPSIS

* OBESITY CTA

HYPERCOAGULABILITY

* MALIGNANCIES * PREGNANCY

WHO ARE AT RISK?

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HIV infection

•Younger HIV patients •CD4+ COUNT <200 /mm3

•Development of AIDS •APAS

•Protein C & S deficiency •Exposure to protease inhibitors •Opportunistic infections

WHO ARE AT RISK?

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“STASIS” MOST COMMON RISK FACTOR IMPLICATED IN “SILENT” VTE

In medically ill patients (excluding those admitted for trauma, mental disorder or for VTE alone), risk for VTE include: 1) history of VTE (w/in 6 months) or surgery (w/in 30 days) 2) ICU admission 3) admission for heart failure 4) active cancer Am J Health Sys Pharm 2006

In medically ill patients (excluding those admitted for trauma, mental disorder or for VTE alone), risk for VTE include: 1) history of VTE (w/in 6 months) or surgery (w/in 30 days) 2) ICU admission 3) admission for heart failure 4) active cancer Am J Health Sys Pharm 2006

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So … what IS the problem?

MOST hospitalized patients have at least one risk factor for VTE

VTE risk increases 260 fold (!) in hospitalized patients Mayo Clin Proc 2001; 76:1102-10

VTE is “silent” in the majority of cases

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THROMBOSIS

BLOOD MOVES SLOWEST AT THE PERIPHERY OF THE VEIN

…COLLECTS IN ONE OR BOTH VENOUS VALVE CUSPS

…BECOMES STICKY, GATHERING AT VEIN WALL

…BECOMES A CLOT THAT CAN GROW BIG ENOUGH TO

CLOSE OFF A VEIN

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VENOUS THROMBOEMBOLISM

Reduced LV inflow

Reduced CO

Cardio- Vascular

compromise

Abrupt Occlusion Pulmonary

vessel

Pulm HPN & RV strain

Reduced pulmonary perfusion

Pulmonary infarct

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Is this problem prevalent ?

VTE risk even higher in the non- surgical critically ill

DVT estimated to occur within the first week of ICU stay in 30% of

patients who do NOT receive

prophylaxis

Arch Intern Med. 2001; 161:1268-79

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What is the impact of VTE in critical care?

Incidence ~ 1.59 % for admissions excluding trauma, labor, surgery, mental disorder

Edelsberg J, Hagiwara M

Am J Health Sys Pharm2006

26% of undiagnosed VTE develop fatal embolic event; another 26% have recurrent embolic events!

Edelsberg J, Hagiwara M

Am J Health Sys Pharm2006

What is the implication for the clinician?

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30 % of PE die within the first few hours of onset; even w/ anticoagulation, PE mortality at 14 and 90 days is 10% & 20%

www.nhlbi.nih/health-topics/pe www.vascularweb.org Task force on PE, Eur J Cardiol 2000

~ 5-10% of in-hospital deaths are due to PE

Lindblad B, Sternby NH etal. BMJ 1991

Sandler DA, Martin JF. R Soc Med 1989

Alikhan R, Peters F etal. J Clin Path 2004

post-mortem meta-analysis indicates: in the last 30 years, clinicians miss 70% of PE!

Pineda LA, Hathwar VS etal. Chest 2001

Rizkallah J, man SF etal. Chest 2009

Ageno W, Agnelli G etal. MASTER registry. Thromb Res 2008

Why is it overlooked so often?

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Shortness of breath is the most frequent presentation of VTE

not all things that seem alike are

alike

Concurrence of cardiovascular co- morbidities tends to delay the diagnosis of VTE because of similarity of presentation

Smith SB, Geske JB etal. J Emerg Med 2012

How should we approach the problem of VTE prophylaxis?

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Estimate VTE risk Estimate bleeding risk

VTE risk > bleeding risk?

Initiate pharmacologic prophylactic therapy

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major surgery most

important risk factor

Most important independent predictors

in medically ill: ICU admission, CHF,

neoplasms, neurologic disease w/ paresis, thrombophlebitis

Arch Int Med 2001;160: 809-15

Am J Health-Sys Pharm 2006; 63(20): S16-22

Estimate VTE risk

Active cancer (treatment or palliation w/in 6 months 1 Paralysis, paresis or recent (4 weeks) plaster immobilization 1 Recently bedridden > 3days &/or major surgery w/in 4 weeks 1 Localized tenderness along distribution of deep vein 1 Thigh and calf swollen 1 Calf swelling 3 cm greater than unaffected side (measured 10 cm below tibial tuberosity

1

Pitting edema on symptomatic leg only 1 Dilated superficial vein (non-varicose) in symptomatic leg only 1

* Score minus 2 if an alternative diagnosis is available High probability > 3 pts Moderate probability 1-2 pts Low < 0 Wells PS, Hirsch J etal.

J Intern Med 1998; 243:15-23

Clinical Scoring System for DVT

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Le Gal G, Righini M etal

(revised Geneva Score)Ann Intern Med 2006

“Combined” Wells & Geneva scoring for prediction of PE:

1) Hemoptysis 2) Tachycardia 3) Malignancy 4) Age > 65 years 5) History of VTE 6) Recent immobilization 7) Current symptoms of DVT

Wells PS, Anderson DR etal

Thromb Haemost 2000

> 4: PE likely < 4: PE unlikely

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PERC (Pulmonary Embolism Rule-out Criteria)

Carpenter CR, Keim SM etal

J Emerg Med 2009

Sinh B, Chnadra S etal

Ann IEmerg Med 2011

(+) all 8 criteria low enough probability to defer D-dimer determination

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1) Age < 50 years 2) Pulse < 100/min 3) Pulse oximetry > 94% 4) Absence of unilateral leg swelling 5) No history of VTE 6) No hemoptysis 7) No recent surgery 8) No oral hormones

Why shouldn’t we give prophylaxis for every patient admitted to the ICU?

BLEEDING !

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VTE risk > bleeding risk?

H - Hypertension 1

A - Abnormal liver function - Abnormal renal function

1 1

S - Stroke 1

B - Bleeding (anemia or predisposition to bleed) 1

L - Labile INRs 1

E - Elderly (age > 65 years) 1

D - Drug use (concomitant NSAID, anti-platelet) - Alcohol use (> 8 alcoholic drinks/week)

1 1

0 1.13 bleed/100 1 1.02 bleed/100 2 1.88 bleed/100 3 3.74 bleed/100 4 8.70 bleed/100 5 12.50 bleed/100

Pisters R, Lane DA etal. The Euro Heart Survey

Chest 2010; 138: 1093-100

HAS-BLED scoring for estimation of Bleeding Risk

Increasing score correlates With increasing bleeding risk

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VTE

prophylaxis

ANTI-PLATELET AGENTS

ANTI- COAGULANTS

Initiate pharmacologic prophylactic therapy

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L LDL

L LDL

L LDL

ARTERIAL THROMBOSIS

VENOUS THROMBOSIS

FORMED UNDER HIGH SHEAR FORCES

FORMED UNDER LOWER SHEAR FORCES

THROMBI are PREDOMINANTLY

PLATELET in COMPOSITION

FEWER PLATELETS in THROMBUS: RBC

& FIBRIN MAKE UP MOST OF THROMBUS

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L LDL

L LDL

L LDL

ARTERIAL THROMBOSIS

VENOUS THROMBOSIS

SIMILAR and DISSIMILAR?

PRESENCE OF MICRO-ALBUMINURIA

PREDICTS BOTH ARTERIAL & VENOUS DISEASE

L LDL

L LDL

L LDL

ARTERIAL THROMBOSIS

VENOUS THROMBOSIS

ANTI- PLATELET AGENTS

ANTI- COAGULANTS

FIBRINOLYTIC AGENTS

ANTI- PLATELET AGENTS

FIBRINOLYTIC AGENTS

ANTI- COAGULANTS

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COAGULATION PATHWAYS & ANTICOAGULANTS

•Vitamin K antagonists •Direct FXa inhibitors •Heparin / LMWH •Pentasaccharides

•Direct Thrombin Inhibitors

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HEPARIN

or

Related

drugs

FRIEND OR

FOE

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HEPARIN

Bleeding risk Major bleeding events

PE events Symptomatic DVT VTE-related mortality

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Are all critical care patients candidates for pharmacologic VTE prophylaxis?

Though less than the incidence in patients undergoing major surgery, the risk of VTE in the medically ill is NOT NEGLIGIBLE Highest risk include those with * recent history of VTE or surgery * admission to ICU * heart failure * active cancer

Edelsberg J,Hagiwara M etal. Am J Health Sys Pharm 2006

Kakkar AK, New Eng J Med 2011

RCT: 8300 acutely ill patients decompensated CHF active cancer severe systemic infection plus Chronic Lung Disease obesity previous VTE advanced (>60 years) age

PHARMACOLOGIC THROMBOPROPHYLAXIS

DID NOT REDUCE RISK OF P.E., SUDDEN DEATH,

CARDIOPULMONARY DEATH BUT DID REDUCE

INCIDENCE OF DVT

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BUT …

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CURRENT STAND

The American College of Physicians DOES NOT support the application of performance measures in medical patients that promotes universal VTE prophylaxis regardless of risk

Amir Q, Chou R etal

for the Clinical Guidelines Committee of the ACP ACP Clinical Practice 2011

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Summary

VTE in ICU a significant problem? Is failure to initiate VTE prophylaxis where appropriate dangerous?

YES

YES

Is there a guide to making pharmacologic prophylaxis better than educated guesswork?

YES

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Admitted for medical illness

Assess for VTE risk

Assess for bleeding risk

VTE risk OUTWEIGHS bleeding risk

Bleeding risk OUTWEIGHS

VTE risk

Weigh VTE risk against

bleeding risk

PROPHYLAXIS

NONE

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SUMMARY of CURRENT RECOMMENDATIONS

Mechanical prophylaxis against VTE with graduated compression stockings IS NOT recommended

Pharmacologic prophylaxis with heparin or related drugs is appropriate in medically ill patients with significant VTE risk where the risk outweighs the bleeding risk

Amir Q, Chou R etal

for the Clinical Guidelines Committee of the ACP ACP Clinical Practice 2011

PRIMUM NON

NOCERE CTA

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