Venous Thromboembolism

Denise Watt

January 3, 2002

Outline

epidemiology pathophysiology risk factors diagnosis

• clinical• labs• diagnostic imaging• algorithms

treatment

Case 1

Rural ED 72 yo male fever, SOB, pleuritic CP x 2 days HR 110, bp 140/90, RR 22, sat 90% CXR unremarkable what test/Rx?

Case 2

55 yo man sudden central CP, SOB, presyncope HR 120, bp 90/70, RR 30, sats 88% ECG: sinus tach what tests/Rx?

Case 3

33 yo healthy woman, 34 wks GA syncope at home EMS called asystolic arrest en route CPR x 5 min what do you do?

Epidemiology

Lifetime incidence VTE 2-5%• PE: 0.5/1,000/year• DVT: 1/1,100/year

PE mortality:• 10% die in 1st hour• 30% untreated• 2-8% if anticoagulated

>50% PEs undiagnosed

Risk Factors

Primary• Factor V leiden• Antithrombin III

deficiency• Prot C deficiency• Prot S deficiency• hyperhomo-

cysteinemia• anticardiolipin Ab• dysfibrinogenemia

Secondary• age• trauma / surgery• malignancy• immobilization• stroke• smoking• obesity• OCP/HRT• lupus anticoagulant• pregnancy• hyperviscosity• heart failure

Risk Factors

50% without risk factors OCP/HRT: 3x baseline risk

• 0.3/10,000/yr; 15/10,000/yr• higher in 3rd gen progesterones

pregnancy: 5x baseline risk• 75% DVT antepartum, 66% PE

postpartum

Pathophysiology:Source of VTE

• most start in calf, extend proximally• 70% PE have DVT evidence at autopsy• 70-90% known source: IVC, ileofemoral

or pelvic veins, 10-20% SVC• incidence of PE from DVT

• calf: 46%• thigh: 67%• pelvic: 77%

• other: UE, jugular, mesenteric, cerebral

Consequences of PE

Hemodynamic• tachycardia• hypotension• RV overload and

dilation CVP LV preload myocardial flow • pulmonary HTN• pul A-V shunts

Respiratory• hyperventilation• PA HTN compliance• atelectasis• broncho-

constriction airway resistance

Clinical Presentation:DVT

Calf-popliteal• 80-90%, many asymptomatic• pain & swelling• spreads proximally

Ileofemoral• pain in buttock, groin• thigh swelling• 10-20% cases

Clinical Prediction Model for DVTWells et al. Ann Int Med, 1997

Score Active cancer 1 Paralysis,plaster immobilization

1

Immobilzation 1 Leg tenderness of deep veins

1

Entire leg swollen 1 Calf swelling >3cm 1 Pitting edema 1 Dilated superficial veins 1 Alternative diagnosis for DVT

-2

Clinical Model for DVT

Pre-test probability Score

High 3

Moderate 1 or 2

Low 0

Incidence of DVT by Clinical Probability

01020304050

60708090

100

Low Mod High Overall

Wells, 1997

Perrier, 1999

Clinical Presentation of PE:The great pretender

SOB, CP or tachypnea in 97% individual s+s not sensitive/specific peripheral (distal vessel)

• pleuritic CP, ± hemoptysis, ± SOBOE central (lobar / segmental)

• SOBOE massive (main pulmonary artery)

• syncope, hypotension, shock

Clinical Prediction Model for PEWells. Ann Int Med, 1998

Score Active cancer 1.0 Hemoptysis 1.0 Recent surgery 1.5 Previous VTE 1.5 HR > 100 1.5 Clinical signs DVT 3.0 No alternate diagnosis 3.0

Pre-test probability High 6 Moderate 2.5-5.5 Low 2

Incidence of PE by Clinical Probability

0

10

20

30

40

50

60

70

80

Low Mod High Overall

PIOPED, 1990

Wells, 1998

Perrier, 1999

Ancillary tests for PE

CXR:• r/o other diagnoses• ‘classic’ signs non-specific

ABG:• 20% have normal PaO2• 15-20% have normal Aa gradient

ECG: • remember???

D-dimer

degradation product of fibrin PPV poor; NPV excellent non-specific:

• +ve: surgery, trauma, hemorrhage, CA• 90% +ve >80 yrs old

most useful in ED patients NOT to r/o PE in high PTP

D-dimer AssaysVan der Graaf. Thromb Haemost, 2000.

Assay Ease of use

Sensitivity Specificity

Whole blood agglutination (SimpliRED)

++++ 80-85% 70-90%

Latex agglutination

+++ 90-95% 40-90%

Rapid ELISA ++++ 95-100% 30-60%

Diagnostic Imaging for DVT

Duplex / compression U/S• non-invasive, portable• direct visualization of veins and flow• loss of compression = DVT• 97% sensitive & specific for

symptomatic proximal/popliteal DVT• 62% sensitive for asymptomatic DVT• +ve in 30-50% PE; 5% non-dx V/Q scans

Serial Venous U/S

2 protocols: Wells & Hull may avoid angiography in ?PE 2% +ve in 2 weeks (?PE) if U/S -ve 2 weeks apart, <2% have

VTE in next 6 mos

Diagnostic Imaging for DVT

IPG• detects changes in flow before and after

cuff inflated• sensitivity 60%

Algorithm for Suspected first DVT:Perrier. Lancet, 1999

+trea t for D VT

LowD VT excluded

-D VT excluded

+trea t for D VT

Mod/H ighseria l U /S

-consider c linica l proba bility

+U /S

- D VT excluded

D -dim er

suspected D VT

Diagnostic Imaging for PE:V/Q scan

PIOPED: ventilation component adds little info

PISAPED criteria:• normal, non-diagnostic, high probability• 25%, 50%, 25% respectively• high prob: 85-90% PPV• non-diagnostic: 25% PE

interpret in context of PTP

Diagnostic Imaging for PE:Pulmonary Angiography

Gold standard (imperfect)• sens 98%, spec 95-98%

ED physicians reluctant to use:• invasive, risks, requires expertise, not

readily available, time consuming, $ relative contraindications indicated if non-invasive tests

inconclusive

Diagnostic Imaging for PE:Spiral CT

IV contrast, direct visualization subsegmental PE not well seen more specific, underlying lung dx sens depends on CT, experience wide variation in studies

• Rathbun. Ann Intern Med, 2000 (review)• sens 53-100%, spec 81-100%• poor methodolgy of studies

Spiral CT

Perrier. Ann Intern Med, 2001• sens 70%, spec 91% , 4% inconclusive• good interobserver agreement

CT venography:• benefit over U/S not determined

role? • no evidence to withold Rx if CT negative• may replace angiography

Diagnostic Imaging in PE:Echocardiography

useful for patients in shock/arrest • r/o DDx: tamponade, Ao dissection, AMI

indirect evidence of PE:• RV overload, septal shift to L, TR, PA

pressure, RV wall motion abn • sens 93%, spec 81%

‘sub-massive’ PE: independent predictor of mortality (?significance)

Algorithm for suspected PE:Wells. Ann Int Med, 2001

-PE exc luded

+

L owD -dim er

norm a lPE exc luded

L ow

PE exc luded

-

seria l U /S

+

M od D -dim er

seria l U /S

-

angiography

+

HighD -dim er

- D V Tcons ider PT P

+ D V T

non-diagnosticleg U/S

high probabi l i tytrea t for PE

V /Q

M od/HighD -dim er

PT P

Wells’ Algorithm:Criticism

Uses SimpliRED assay: lower sens. sCT not included

• could replace angiography? Low prevalence of PE (9%) not validated by other RCTs

Treatment of VTE:Goals

reduce mortality prevent extension/recurrence restore pulmonary vascular

resistance prevent pulmonary hypertension

Treatment of VTE:Anticoagulation

Out-patient LMWH LMWH superior to UFH? (Gould 1999)

out-pt Rx safe in PE (Kovacs, 2000)

DVT: start Rx, definitive test in 24hr baseline B/W

Anticoagulation

Enoxaparin 1mg/kg bid or 1.5 od Tinzaparin 175 anti-Xa u/kg od start warfarin 5mg on day 1 d/c LMWH when INR >2.0 x 2 days Rx 3 mos if 1st and reversible cause 6 mos if non-reversbile indefinite if recurrent, CA, genetic

Treatment of PE:Criteria for admission

Hemodynamic instability O2 requirement surgery < 48hr risk of active bleeding history of HIT IV pain control

Treatment of massive PE

judicious fluids (500cc max) NE, dopamine, dobutamine prn O2, intubate if shock

• positive pressure worsens RV fn anticoagulation

• if no contraindications• UFH if hypotensive• PTT 1.5-2.5 x normal

Treatment of massive PE:Thrombolytics

no evidence of mortality benefit• including in cardiac arrest (case series)

no benefit in hemodynamically stable improves pul. perfusion (15% vs 2%),

RV function (34% vs. 17%) cf. heparin t-PA faster hemodynamic effect IV same as intrapulmonary 5-10% major bleed, 1-2% ICH

Thrombolytics

2 week window of opportunity!• effect with time

no advantage of t-PA bolus protocols:

• t-PA: 100mg over 2 hr• UK: 4400U/kg over 10min; rpt x 12-24hr• SK: 250,000U over 30min; 100,000 x 24h• arrest: t-PA 10mg/kg bolus x 2 q 30 min

Embolectomy

Indicated in acute, massive PE if:• contraindication to thrombolytics• unresponsive to medical mgt

moribund pt poor results no evidence cf. with thrombolytics percutaneous vs. surgical

• ?role

IVC Filters

Indications:• contraindication to anticoagulation• recurrent VTE despite anticoagulation• after surgical embolectomy

no long term adv vs. anticoagulation anticoagulate if no contraindications

• DVT and IVC occlusion

Pregnancy

V/Q safe, no breastfeed x 15hr post D-dimer in pregnancy, wide Aa angiography safer than empiric Rx LMWH in DVT, not studied in PE PE: UFH IV x 4-5 days, then s/c treat x 3 months or 6 weeks postpartum switch to oral postpartum