venous thromboembolism
DESCRIPTION
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% - PowerPoint PPT PresentationTRANSCRIPT
Venous Thromboembolism
Denise WattJanuary 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
0102030405060708090
100
Low Mod High Overall
Wells, 1997Perrier, 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
01020304050607080
Low Mod High Overall
PIOPED, 1990Wells, 1998Perrier, 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 V T
LowD VT excluded
-D VT excluded
+trea t for D V T
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 e xc lude d
+
L owD -dim e r
norm alPE e x c lude d
L ow
PE exc luded
-
se ria l U/S
+
M od D -dim er
se ria l U /S
-
a ngiogra phy
+
HighD -dim e r
- D V Tc ons ider PT P
+ D V T
non-diagnosticleg U/S
high probabi li tytrea t for PE
V /Q
M od/H ighD -dim e r
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