DVT & PE James Huffman & Dr. Trevor Langhan 11.12.2009.
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Transcript of DVT & PE James Huffman & Dr. Trevor Langhan 11.12.2009.
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DVT & PE
James Huffman & Dr. Trevor Langhan
11.12.2009
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• DVT– Diagnostic Algorithm– Determining Pre-test Probability– Useful Diagnostics– Treatment– Disposition– Special Circumstances
• PE– Similar topics, PLUS:– Controversies
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Virchow’s TriadWhite, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003.
1. Injury to the vascular endothelium
2. Alterations in blood flow3. Hypercoagulability
Anything else associated with imbalanced clot formation?
Age
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Case 1
• 55♀: Referred to ED for pain, redness and swelling of the right calf– WIC today: Sent to ED with note:
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Diagnostic Approach: Pre-test ProbabilityScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087
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DVT: History & PE are Risk Assessment
• Goals of H&P?– Determine pre-test
probability– Look for other causes
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Case 1: History & Physical Exam
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History & Physical are Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)
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DVT: H&P Bottom Line
• Neither is sensitive or specific– i.e. you can’t rule-in or rule-out a DVT
• Use them to decide pre-test probability
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Pretest Probability
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Pretest Probability
• This algorithm re-presented in JAMA rational clinical examination series
Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this patient have deep vein thrombosis? JAMA. 1998 Dec 2;280(21):1828-9.
• What’s missing?
The Dimer!
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D-Dimer TestingKline, et al. Ann Emerg Med (2003); 42(2): 266-275.
Degradation product of fibrin
Non-specific
– PPV bad
– +ve: surgery, trauma, hemorrhage, CA, pregnancy, sepsis, >80 yrs old
Sensitivity variable
Need Pre-test probability to r/o DVT
Assay
Sensitivity Specificity
Whole blood agglutination (SimpliRED)
80-85% 70-90%
Latex agglutination
90-95% 40-90%
Rapid ELISA 95-100% 30-60%
CLS uses
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Clinical Variable Score
“Active” Cancer (treatment ongoing, within 6 months or palliative) 1
Paralysis, Paresis or recent casting of lower extremities 1
Recently bedridden 3 days or more, or Surgery A in past 3 months 1
Localized tenderness along distribution of deep venous system 1
Entire leg swollen 1
Calf swelling at least 3cm larger than asymptomatic leg 1
Pitting edema confined to the symptomatic leg 1
Collateral superficial veins (Non-varicose) 1
Previously documented DVT 1
Alternative Diagnosis at least as likely as DVT -2
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D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35
RCT (N=1096)
D-Dimer vs no D-Dimer
DVT unlikely (Wells < 2)
# of U/S per pt decreased in D-dimer group (0.78 vs 1.34)
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D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35
• “Modified” Wells Criteria
• Used SimpliRED and IL-Test assays (less sens than ours)
• Conclusion:
– Wells <2 and negative D-Dimer can safely r/o DVT
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Level 1 – Pretest Probability
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Case 1 continued
• Pretest probability?
– Active cancer (1)
– Localized tenderness (1)
– Calf swelling (1)
– Edema (1)
– Other Diagnosis? Compression by pelvic nodes? (Doesn’t matter – score would still be “not low risk”)
So she gets either 4 or 2 points = DVT likely
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What next Einstein?
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Level 2 – D-dimer
• Her d-dimer was positive at 1.23
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Level 3 – Ultrasound (or not)
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UltrasoundAmerican Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66
Bottom line: U/S is the test of choice for DVT
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Anatomy
• Depth:– Deep– Superficial*
• Proximity:– Popliteal v. or
higher– Distal
*Superficial femoral vein is a member of the deep group
Emerg Med Clin N Am. 26 (2008)
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Ultrasound Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83
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Bedside U/S?
Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32.Frazee BW, et al. J Emerg Med 2001;20(2):107–12.
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• Blaivas M, et al. Acad Emerg Med. 2000;7(2):120–6.– Median exam time of 3m 28s– 98% correlation with vascular lab-performed studies
• Theodoro D, et al. Am J Emerg Med. 2004;22(3):197–200.– 125m reduction in time to pt disposition with EP-performed US– Kappa = 0.9, 99% agreement (154/156 cases)
• Jang T, et al. Acad Emerg Med. 2004;11(3):319–22.– 8 emerg residents (4 PGY-1, 2 PGY-2, 2 PGY-3)– 1h focused training (didactic and practice on 2 healthy
volunteers)– SN = 100%, SP = 91.8%, avg scan time = 11.7min (self-
reported)– 4 false-positives (chronic DVT), 0 false-negatives
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Ultrasound: Limitations
• Obese, ++edema, immobilsation devices (x-fix)
• Doesn’t see isolated thrombi in iliac or superficial femoral veins within abductor canal MRI better
• Pelvic masses may cause noncompressibility in absence of thrombus false +’ve
• Most importantly: U/S doesn’t return to normal after acute DVT
• Therefore use impedance plethysmography for recurrent DVT
– U/S - 60-70% of studies return to normal at one year
– IP – 90% return to normal within a year
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CT-VenographyGoodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6
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DVT: Bottom Line Thus Far?
1. Hx/PE help decide pretest probability (Wells)
2. Add a sensitive test (D-Dimer)
3. Almost all cases, do a sensitive confirmatory test (U/S)
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Case 1 Continued
• Okay back to it…• U/S shows popliteal vein DVT• Management Doctor?
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Level 4 - Treatment
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Medical ManagementRosen’s Emergency Medicine 7th EditionScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087
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Treatment: Bottom Line
• IV UFH, LMWH, Fondaparinux are all acceptable
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Case 1 Conclusion
• Pt started on Enoxaparin and Warfarin • Arranged to see her oncologist and a
hematologist as out-patient 2 days later
• In General, discharge home is safe. • Admission may be required if:
– Renal failure, high bleeding risk– Extensive DVT (painful blue leg)– Necessity for parenteral narcotics– Inability to have injections at home
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Special Circumstances
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Superficial ThrombophlebitisRosen’s Emergency Medicine 7th Edition
• Uncommonly evolves into a thromboemboic event
• BUT, ~8% of patients have synchronous DVT
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Isolated Calf or Saphenous V. ThrombosisCanadian Medical Association Journal. 2003; 168(2)
• Rarely cause significant PE
• 25% of calf DVT extend to involve proximal veins
• Vast majority will extend within 7d
• DVT complications in 10-38% (untreated)
Clinically this means you can Rx ASA (325mg/d) and arrange for re-U/S in 7d or just start on full DVT
anticoagulation
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Phlegmasia Cerulea Dolens (Painful Blue Leg)
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Pulmonary Embolism
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Case 2
• 61♀ presents to ED complaining of mild pleuritic chest pain
– Total knee arthroplasty 5/12 ago. Healthy otherwise
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Risk AssessmentEmergency Medicine Reports. 2004;25(11)
• History and Physical do not confirm the diagnosis, they merely raise the suspicion of the diagnosis, triggering further investigation
• Hx:– Have to consider PE: dyspnea, tachypnea Pleuritic CP,
syncope, hypotension & hemoptysis– Non-specific
• PE:– Tachypnea and tachycardia are most common
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Pretest Probability Emergency Medicine Reports. 2004;25(11)
• All decision rules start w/ score
• Wells and Geneva validated• Wells NPV: 99.5%• Others more cumbersome
• Geneva (Wicki): adds ABG, CXR
• PISA-PED: Adds ECG
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Bottom Line:
Use history & physical exam risk stratify patients
Wells ≤ 4 PE UnlikelyWells > 4 PE Likely
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H&P are Risk AssessmentWells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50
Wells ≤ 4 Unlikely
Wells > 4 Likely
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Risk AssessmentEmergency Medicine Reports. 2004;25(11)
• CXR:
– Often AbN (Pleural effusion, atelectasis, elevated hemidiaphragm)
– N CXR with dyspnea & hypoxemia = PE
– Know Hampton’s and Westermark for exams
• EKG:
– Non-specific ST, Twave changes, Tachy • Signs of R heart strain (Anterior/Inferior T-wave inversions)
– Know SIQIIITIII for exams
– Simultaneous TWI in V1 and III are highly specific
• ABG:
– Hypoxemia common, but not always present
– AAD02 >20 suggests PE (PIOPED)
– 25-35% of pts with PE have normal blood gasses, pulse ox, and A-A gradient
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Case 3 Continued
• HR: 104• Nil else
• She gets 1.5 points
• Now what?• Do you even start to work her up for PE?
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PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55
• Based on the premise that overuse of D-dimer to screen for PE can have negative consequences
• Derivation phase:– 3148 patients evaluated for PE in 10 US EDs– Data collected on 21 variables– Logistic regression and inter-observer agreement used to
narrow to rule of 8.
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PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55
• Age <50 • Pulse rate <100 beats/min • Oxygen saturation >94% • No hemoptysis • No unilateral leg swelling • No recent major surgery or trauma • No prior pulmonary embolism or deep
venous thrombosis • No hormone use
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PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55
• Validation Phase:– 2 Groups:
1. Low risk (board certified EP believed D-dimer warranted but good enough to r/o PE) – n = 1427, 114 (8%) had VTE diagnosed within 90d
2. Very low risk (chief complain dyspnea – PE not suspected)– n = 382, 9 (2.4%) had VTE diagnosed within 90d
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PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55
• Endpoint: VTE before 90 days. Good follow-up• Both Wells score and PERC rule functioned relatively
well– Wells <2 better with very low risk population and
included more patients in both groups– Both had very wide confidence intervals
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PERC Rule – Bottom Line
• Compliments clinical judgment – DOESN’T REPLACE IT!
Pause before ordering a D-dimer in a patient
who does not have any of the eight criteria
Then order it if you still think it’s indicated
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Case 2 Continued
• Age > 50• HR >100• Does not meet PERC criteria. Wells 1.5
– Send the D-dimer– Result: 0.59 mg/L (↑)
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PIOPED I – V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753
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PIOPED I – V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753
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PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
CTA inconclusive: 6%
CTA Sens: 83%, Spec: 96%
CTA-CTV 90% and 95%
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PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
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8-bit vs 64-bit resolution
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• Meta-analysis of 23 studies– Negative CT PE who didn’t receive AC– 4657 patients
• Results (3 month follow up)– VTE: 1.4% (1.1-1.8%)– Fatal PE: 0.51% (0.33-0.76%)
• Conclusions– CTPA has similar rates of recurrence as angiography– Appears safe to withhold anticoagulation based on negative
CTPA
Outcomes: Multi-detector Row CTMoores, L., et al. Ann Intern Med. 2004; 141:866-874
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Bottom Line
Multi-detector row CTPA should be considered the “gold standard”
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Magnetic Resonance AngiographyFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83• Advantages:
– Eliminates radiation– Probably safer in pregnancy– Decreased nephrotoxicity
• Disadvantages:– Cost– Availability– Failure to demonstrate adequate SN in
preliminary studies
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PIOPED III – MR-A
• Purpose
– Determine accuracy of Gd-MRA of pulmonary arteries with MRV of the thigh veins in pts with clinically suspected PE
– Rationale: In PIOPED II, 25% had contraindications to CTPA/Angio such patients could benefit from safer MR
– Expect 1250 pts (lots of exclusions incl Pregnant)
– Calgary is one of the Centres
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Case 3 Continued
• Recall…• Low probability (Wells 1.5)• D-Dimer: Positive• Therefore...
– CTPE Positive
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Treatment Emergency Medicine Reports. 2004;25(12)Houman et al. J Thromb Thrombolysis. 2009. 28:270-7
1. First decide primary therapy– Significant clot burden immediate removal
• Chemical - thrombolysis
• Mechanical – embolectomy
– Less Significant Anticoagulation• UFH, LMWH, (Fondaparinux) Coumadin
• Next decide prevention against future emboli– Anticoagulation– IVC filters
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Spectrum of PEKearon et al. 2008 Chest.
• Massive (PE + shock)– Thrombolysis + ICU
• Submassive (PE + NBP + RV Dysfxn)– Admission, anticoagulation, +/- thrombolysis
• Symptomatic– probable admission, anticoagulated, +/- echo
• Asymptomatic– You probably don’t even know about it ….
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Fibrinolysis Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)
• Massive PE:– PE with systemic arterial hypotension, cardiogenic
shock, severe dyspnea or respiratory failure• Multiple case reports/series of improved outcomes and
ROSC• Kucher et al. 2006: no change in mortality or recurrence of
PE
• Submassive PE:– PE occurring in hemodynamically stable patients
with evidence of right ventricular heart strain, as seen on ECG or echocardiography
• NEJM 2002; 347(15) –100mg alteplase in addition to heparin improves clinical course (ARR = 13.6%, P=0.006)
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Fibrinolysis in sub-massive PERamakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)
Results of randomized trials comparing the addition of thrombolytic therapy to standard heparin therapy for treatment of submassive pulmonary embolism fail to show any significant differences in clinically important outcomes. [Ann Emerg Med. 2007;50:78-84.]
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Fibrinolytics – Bottom Line
Consider in PE with hypotension or systemic hypoperfusion or in the rapidly deteriorating patient
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Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016
1. Is it technically possible?– Newer treatments allow out-pt treatment of VTE
• LMWH• SC UFH
2. Is it safe?– Pts at high risk of “badness” shouldn’t go home
• Massive & Submassive PE – no brainers• Risk stratify the rest:
– Geneva Risk Score– Pulmonary Embolism Severity Index (PESI)
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V. Low Risk = 1.1% 30d Mortality
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GRS vs PESI
• GRS– Sn 34% (18-51)– Sp 85% (82-88)– PPV 11% (5-18)– NPV 96% (94-98)
• PESI– Sn 81% (68-95)– Sp 37% (33-41)– PPV 7% (4-9)– NPV 97% (95-99)
Jimenez. Chest 2007
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Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016
3. Is outpatient treatment appropriate in THIS patient?
– Medical and Social Issues:
• Bleeding risk, underlying malignancy, renal status, obesity, heart failure, thrombophilia, and concomitant medications that interact with anticoagulants (aspirin, clopidogrel, NSAID etc)
• Medication compliance, availability of home-care, living situation, logistics of bloodwork
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Out-Pt Treatment of PE
• Bottom Line:
There is no consensus on who can safely be treated at home
If the patient is hemodynamically stable, with no signs of R heart strain and otherwise completely healthy,
consideration of out-pt treatment is reasonable.
Would make this decision in discussion with pulmonary or the patient’s FP.
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Wait, is she just a little hefty or…?
• Common – VTE most frequent cause of death in pregnancy
– 0.5-3.0 / 1000 pregnancies
• Most trials exclude pregnant pts
• D-Dimer is less specific!
– More false positives more work-up
• US is great…if there’s a DVT
– + in 13-15% with suspected PE
• What about CTPE? V/Q?
• MRI/A not studied yet
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PE in PregnancyWiner-Muram HT, et al. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology 2002;224(2):487–92.
• Historically, V/Q recommended less radiation
• Newer scanners supposed to be better?• V/Q still gives indeterminate results
Average fetal radiation dose with helical CT is less than that with V/Q lung scanning during all trimesters. Pregnancy should not
preclude use of helical CT for the diagnosis of PE.
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PE in PregnancyCook JV, Kyriou J. Radiation from CT and perfusion scanning in pregnancy. BMJ. 2005;331:350.
• Compared maternal and fetal-absorbed doses (16-slice)
• Maternal whole body effective dose:– CTPE: 2 mSv
– V/Q: 0.6 mSv
• Fetal absorbed doses:– CTPE: 0.01mGy (1/1 000 000 risk of Ca by age
15)
– V/Q: 0.12 mGy (1/280 000)
• Breast absorbed doses:– CTPE: 10 mGy
– V/Q: 0.28 mGy
CTPE: less risk to fetus, more to mom’s breasts
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PE in Pregnancy - Treatment
• Same as other populations except Warfarin– Known Teratogen don’t use.
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Bottom Lines
• History and Physical are insensitive and non-specific
– Use them to determine pretest probability
• D-dimer is a sensitive screening test
– But not benign – use your head
– Remember PERC “rule” – only a guideline
• CTPE is very powerful
– If neg – safe to withhold treatment
• Fibrinolysis if hypotensive, hypoperfused or circling
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Pretest Probability Wells, P, et al. 1997. Lancet:350;1795.
593 pts w/ suspect DVT Stratified low, mod, high risk compression U/S /veno 3% of Low risk, 17% of moderate risk, 75% of high risk pts
had DVT Concluded that Clinical probability + U/S safe [0.6% missed]
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Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolismVan Dongen C. Cochrane Review 2005
• 22 studies (n = 8867)
• Thrombotic complications (18 trials)– LMWH = 151/4181 (3.6%)– UFH 211/3941 (5.4%)– OR 0.68; (0.55 to 0.84
• Thrombus size was reduced (12 trials)– LMWH= 53%– UFH 45%– OR 0.69 (0.59 to 0.81)
• Major hemorrhages (19 trials)– LMWH = 41/3500 (1.2%)– UFH 73/3624 (2.0%)– OR 0.57 (0.39 to 0.83)
• Mortality (18 trials)– LMWH 187/4193 (4.5%)– UFH 233/3861 (6.0%) – OR 0.76 (0.62 to 0.92)
• BID dosing ? Better– CI for OR crossed 0
Aric 2005
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FondaparinuxMatisse Investigators. Ann Intern Med. 2004;140:867-73.
• Synthetic polysaccharide• Anti Factor Xa• DBRCT Fondaparinux vs Enoxaparin in symptomatic DVT
– 2205 pts with symptomatic DVT from 154 centres worldwide– Fondaparinux 7.5mg*sc od vs Enoxaparin 1mg/kg sc bid– Outcomes:
• Symptomatic recurrent VTE• Bleeding• Death
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Fondaparinux Matisse Investigators. Ann Intern Med. 2004;140:867-73.
• At least as safe and effective as LMH• To date: no reported heparin-induced
thrombocytopenia
• However, not available in Canada at this time
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