PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS
James Huffman Thanks to Dr. Gil Curry, Dr. Nadim Lalani

Outline Epidemiology / Pathophysiology DVT Real-Life Algorithm
Anatomy Clinical Presentation Diagnostic Approach Pre-test probability Labs Imaging Real-Life Algorithm Treatment

Outline PE Clinical Presentation Diagnostic Approach
Pre-test probability Labs EKG Imaging X-ray, CT, MR Real-Life Algorithm

Focus: the bottom line

Epidemiology VTE is a ‘spectrum’ : Simple superficial thrombophlebitis to fatal PE Est incidence : 100 / 1/3 of cases are PE Increases dramatically with age (sharp increase after the age of 45) DVT: Only 1/3 of pts investigated for DVT have it “silent” PE present in 40-60% of pts with DVT In asymptomatic pts w/ proven DVT, up to 1/3 will have undiagnosed PE With treatment 50% have residual clot up to 1y Without treatment 50% recurrence w/ in 3 mo Cases/ in those younger than 15 500 cases/ in those older than 80 SHARP increase after the age of 45

Epidemiology PE: Complications: 10% fatal w/ in 1st Hour
75% pt w/ PE have DVT (2/3 proximal vein) Classic presentations are less common than atypicals and asymptomatic VTE is common 20% have “pleuritic CP” in ED 5-10% PE have shock as initial presentation Despite treatment, kills 1-8% Complications: postphlebitic syndrome [40%] pulmonary HTN [4%] PE has an untreated mortality of 26-30% and one autopsy review found that 70% of PE’s were not suspected clinically

Pathophysiology of Thrombosis
Fibrinogen is converted to fibrin in response to vasc. Injury and inflammation Fibrin is 1° structural framework of embolized clots and excessive fibrin deposition provides the nidus of VTE VTE is the end-product of imbalanced clot formation and breakdown What promotes this imbalance of fibrin deposition and removal?

Injury to the vascular endothelium Alterations in blood flow
Virchow’s Triad White, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003. Injury to the vascular endothelium Alterations in blood flow Hypercoagulability Anything else associated with imbalanced clot formation? Age – likely through a combination of the above mechanisms Vascular injury initiates release of tissue factor that activates factor 10a and leads to increased fibrin formation and deposition. Venous stasis allow for increasd fibrin cross-linking Clinical states that involve the presence of Virchow’s triad result in a higher incidence of VTE

Coagulation Cascade

Coagulation Cascade PTT Heparin PT/INR Warfarin

Anatomy Depth Proximal Distal Popliteal v. or higher
Deep Superficial* Proximal Popliteal v. or higher Distal *Superficial femoral vein is a member of the deep group Superficial Femoral Vein is indeed a member of the deep group. Although thrombosis can occur anywhere in the venous system, it typically forms at locations of injury or stasis, particularly in the valve cusps in the venous sinuses of the calf veins. Only thrombus from deeper and more proximal vessels are believed to embolize to the lungs. For this reason, the venous system is divided by proximity and depth. Although distal DVTs are generally not thought to pose an immediate threat to embolization, there is a 20% to 30% incidence of propagation to the proximal venous system. Clinically significant thrombosis can also involve pelvic veins, upper extremity veins, and venous sinuses of the skull.

Case 1 55♀: Referred to ED for pain, redness and swelling of right calf WIC today: Sent to ED with note: Nurse tells you it says “please r/o DVT”. Where do you want to start?

History Started 3/7 ago Denies previous DVT
Has been on IV combo chemotherapy for ovarian Ca diagnosed six months ago (extensive pelvic lymph node involvement – which has improved as per recent U/S) Fell day before this started and “twisted her knee” All this is good – what are your main goals with history? Determine pre-test probability of DVT Look for other causes The history and physical examination are helpful in suggesting the diagnosis, but no one sign or symptom in isolation maintains significant sensitivity or specificity for DVT

DVT: History is Risk Assessment
Hypercoagulability: Autoimmune Disease and Immune Deficiency Not just SLE! Remember IBD Cancer Chemotherapy: especially breast CA Coagulopathy:  Factor V Leiden. Present in 7% pop = 50%  Protein C, protein S & antithrombin III deficiency = 15% DVT.  Resistance to aPC  Lupus anticoagulant  Prothrombin G20210A  antiphospholipid antibodies  others

DVT: History is Risk Assessment
Stasis: Immobility: Not just surgery – remember other conditions (oldies!) Heart Disease (AMI & CHF): independent of bedrest Travel ?Duration / proximity? Hyperlipiedmia Polycythemia Endothelial Injury: Stroke Vascular surgery PVD Others: Age, race, prior DVT, blood types, tissue antigens, homocysteine

Case 1 Continued When you examine her what do you expect to find? P/E:
Generalised tenderness to her calf Exquisite pain in popliteal fossa along vein Edema, erythema and warmth Swollen 3.5 cm Homan’s Sign + What do you think of this?

Neither sensitive nor specific OR’s between 2- 4
Physical is Risk Assessment Anand, SS, Wells, PS, et al Does this Patient have deep vein thrombosis? JAMA:279(14) Classically: Leg tenderness , Homan’s Sign Swelling Pitting edema Dilated superficial veins Erythema Calor Neither sensitive nor specific OR’s between 2- 4 Although symptoms are less frequent with smaller and more distal clots, large proximal clots may also be asymptomatic in the presence of adequate collateral veins and patency of vessels. The clinical signs and symptoms of DVT are often found in many other conditions affecting the lower extremity including musculoskeletal injuries, cellulitis, ruptured Baker’s cyst, vasculitis, congestive heart failure, lymphedema, and other nonthrombotic conditions. Laboratory and radiologic testing are fundamental in the diagnosis of DVT

Physical is Risk Assessment Anand, SS, Wells, PS, et al. 1998
Physical is Risk Assessment Anand, SS, Wells, PS, et al Does this Patient have deep vein thrombosis? JAMA:279(14)

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 We need to remember that although making the diagnosis of DVT by history and physical examination alone is inadequate, performing radiologic testing on all patients is unnecessary and inefficient. Implementation of clinical prediction rules to assess a patient’s pretest probability could reduce the need for formal radiologic studies to rule out DVT.

Clinical Prediction Rule: Evolution Landefeld et. Al 1990
354 pts suspected of DVT that underwent venography 5 clinical predictors identified: 1 or more  95% Sens [92-100] 20% spec [15-25] Swelling above the knee Swelling below the knee Recent immobility Fever Cancer Absence of all  only 5% DVT Relatively small study

Pretest Probability Wells, P. , et al. 1995
Pretest Probability Wells, P., et al Accuracy of Clinical Assessment of Deep Vein Thrombosis. Lancet:345; First Wells Criteria Based on literature review and clinical experience of investigators Study showed value in stratifying pretest probability with respect to eliminating need for repeat u/s

Pretest Probability Wells, P, et al. 1997. Lancet:350;1795.
Revised Wells score through logistic regression analysis Prospectively validated using same treatment algorithm (next slide) 593 patients from two Canadian tertiary care centres Score ≥ 3 (high risk), 1 or 2 (moderate risk), <1 (low risk)

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]

Pretest Probability The N’Dimer!
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 Dec 2;280(21): What’s missing? D-dimer - Use evolving concurrently with above studies The N’Dimer!

D-Dimer Testing U/S not a perfect test 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 90 95% 40 R apid ELISA 95 100% 30 60% D-dimer is an end product of clot lysis. When it’s there, it signifies the existence of thrombus with an active deposition and degradation of cross-linked fibrin by plasmin somewhere in the body. Small amounts of D-dimer are normally present in the serum; however, elevated D-dimer levels correlate with increased thrombus volume. The problem with the test is that it doesn’t discriminate between physiologic (eg, postoperative or post-trauma) and pathologic (eg, deep vein) thrombus. D-dimer levels may also be elevated in cancer, late pregnancy, recent trauma or surgery, sepsis, and many other medical conditions, limiting its use. For these reasons the D-dimer is a sensitive, but nonspecific test. QUESTION: Causes for a false-negative D-dimer test include small amounts of thrombus, old thrombus, and impaired fibrinolysis. CHR uses

D-Dimer Testing Wells, P., et al. 2003. NEJM: 349(13); pp1227-35
RCT (N=1096) D-Dimer vs no D-Dimer DVT Likely = Wells ≥ 2 # of U/S per pt decreased in D-dimer group (0.78 vs 1.34) In 2003, Wells and colleagues showed that a negative whole-blood agglutination or immunoturbidimetric D-dimer test eliminated the need for ultrasound in low-risk patients. Although a negative D-dimer test does not eliminate the need for ultrasound in the intermediate and high-risk population.

D-Dimer Testing Wells, P., et al. 2003. NEJM: 349(13); pp1227-35
“Modified” Wells Criteria Used SimpliRED and IL-Test assays (less sens) Conclusion: Clinical prediction rule + D- Dimer can safely r/o DVT

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”) What about the D-Dimer – Would you order it? Doesn’t matter – it was sent already Level positive at 1.77C Both CMAJ and Well’s protocols would have you order it anyway (we’ll discuss) So she gets either 4 or 2 points = DVT likely Nursing should not be ordering D-dimer – not part of the protocol *possible discussion around what to do with the positive Dimer you didn’t order (handover, nursing, etc)

What next Einstein?

Bottom line: U/S is the test of choice for DVT
Ultrasound American Journal of Respiratory Critical Care Medicine. 1999: 160; Well studied Widely available Proven accurate for Dx symptomatic prox DVT Like CT/PE provides other Dx: hematomas, baker’s cysts, lymphad, aneurism, thrombophlebitis and abscess Has been advanced by the combination of compression and doppler Bottom line: U/S is the test of choice for DVT Ultrasound is the test of choice for diagnosis of DVT. It is fast, accurate, and readily available in most EDs. Since the 1990s, ultrasound has replaced venography as the gold standard for DVT because it provides nearly equal diagnostic information while avoiding the risks of invasive venography, (which has a 2% chance of inducing DVT.)

Duplex Ultrasound Stork, A. 2005. Calgarian J of PPT Slides. 1(1) pp1
Two parts i) Compression - Tech applies pressure - clot  not compressible ii) Doppler (B mode) Shows blood flow The two methods of ultrasound commonly used when assessing DVT are compression and duplex. Compression ultrasound works by the principle that normal veins collapse when extrinsic pressure is applied by the sonographer. When a vein fails to collapse, it indicates the presence of an intravascular mass (thrombus by default). Duplex ultrasound is compression ultrasound with the addition of spectral and color flow Doppler to assess respiratory variation and augmentation.

Ultrasound Fields, JM, & Goyal, M. Venothromboembolism
Ultrasound Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: In contrast to compression ultrasonography, duplex is relatively complicated, time consuming, and expensive. Despite these characteristics, it adds little to compression ultrasonography in the diagnosis of DVT. When performing compression ultrasonography, assessment of the entire proximal venous system is unnecessary to rule out proximal DVT. In a study of 562 venograms performed on patients with DVT, no cases of isolated superficial femoral or pelvic vein thrombosis were identified. All DVTs involved either the popliteal, common femoral, or both veins. This has led to the development of limited compression ultrasonography (LCUS). LCUS is compression ultrasonography focused on the common femoral and popliteal veins. Despite rare case reports of isolated superficial femoral DVTs, studies have demonstrated the safety of withholding anticoagulation after negative LCUS. BUT – we don’t do this here

EDE Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32.
Retrospective analysis 1994 EPs trained to perform colour doppler US (20-30 studies each) 100% sensitive, 75% specific for acute DVT 2 false-positives were in chronic DVT Frazee BW, et al. J Emerg Med 2001;20(2):107–12. Prospectively demonstrated 95.7% NPV for EP performed LCUS Many clinicians, including emergency physicians (EPs), are performing bedside ultrasonography to evaluate for DVTs. Jolly and colleagues were the first to demonstrate the ability of EPs to perform color Doppler ultrasonography successfully in a retrospective observational analysis in Two EPs performed ultrasounds in the ED after training in a vascular laboratory (performing 25–30 studies each). The sensitivity and specificity of their color Doppler ultrasounds for acute DVTs were 100% (seven of seven) and 75% (six of eight), respectively. The two false-positives were patients with old DVT. In 1999, Frazee prospectively demonstrated a 95.7% negative predictive value (NPV) of EP-performed LCUS.

Naughty by Nature - “Feel me flow”

EDE – ED Flow 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 on same pts 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 So we know we can be accurate, but EPs can also maintain their goal of rapid throughput by performing LCUS. Blaivas demonstrated a median examination time of 3 minutes and 28 seconds of EP-performed LCUS, while maintaining a 98% correlation with vascular laboratory–performed studies on the same patients. Another study by Theodoro observed a 125-minute reduction in time to patient disposition with EP-performed US compared with radiology-performed US while also maintaining good correlation. Jang and colleagues prospectively studied the ability of eight emergency medicine residents with minimal training in LCUS and found a sensitivity and specificity of 100% and 91.8%, respectively, with an average scan time of 11.7 minutes.

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 % of studies return to normal at one year IP – 90% return to normal within a year

CT-Venography Goodman LR, Stein PD, Matta F, et al
CT-Venography Goodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6 PIOPED II Data 711 pts with CT-V and sonography Results: 95.5% concordance for dx or exclusion of proximal DVT Kappa = 0.809 Simlar results across all subgroups (asymptomatic, symptomatic, previous DVT) CT venography (CTV) is a diagnostic modality that evaluates the pelvis, thighs, and calves after injection of venous phase contrast material. It has near equal sensitivity and specificity to ultrasound for diagnosing proximal DVT. Because CT angiography (CTA) of the pulmonary vessels and CTV can be performed simultaneously, CTA-CTV is an attractive option for patients with concern for both DVT and PE. Furthermore, CTV can diagnose pelvic and calf DVTs. Cost, radiation exposure (particularly through the reproductive organs), intravenous contrast exposure, and needfor intravenous access are ongoing concerns about the use of CTV.

Bottom Line Thus Far? ‘Cause Stone Cold says so!
Hx/PE help us decide pretest probability (Wells) We add in a sensitive Test (D-Dimer) And a sensitive confirmatory test (U/S) ‘Cause Stone Cold says so!

Real-Life Approach Scarvelis, D. , and P. Wells. 2006
Real-Life Approach Scarvelis, D., and P. Wells Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087. All patients in the ‘‘DVT likely’’ group should undergo ultrasonography. In patients with a negative LCUS and positive D-dimer test, repeat ultrasonography is recommended to exclude the possibility of distal DVT, which have a 20% to 30% incidence of propagation. Another approach is to administer one dose of LMWH and arrange an outpatient ultrasound within 24 hours.

Or…the 1620h approach Fields, JM, & Goyal, M. Venothromboembolism
Or…the 1620h approach Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: This one get’s the US first

CHR Approach The next 4 slides describe the current Calgary Health Region approach Not many people use this as it is a bit outdated but I’ve kept the slides here for your interest

Wells Criteria for Probability of DVT
LOW PROB < 0 points Clinical Hx/Sign Criteria Points 1. Malignancy receiving active treatment for cancer OR have received treatment for cancer in past 6 mo. OR are receiving palliative care for cancer 1.0 2. Limb immobilization Paralysis OR Paresis OR Recent casting of lower extremity 3. Patient immobilization bedrest (except access to BR) > 3 days OR surgery in previous 4 weeks 4. Localized tenderness Along distribution of deep venous system 5. Entire leg swollen 6. Calf swelling >3cm when compared with asymptomatic leg Measured 10cm below the tibial tuberosity 7. Pitting edema Greater in the symptomatic leg 8. Collateral superficial veins dilated Non-varicose veins 9. Alternative Dx as likely or more likely than that of DVT No specific criteria – use Hx, Physical, CXR, EKG, and labs to decide -2.0 MOD PROB 1 or 2 points HIGH PROB >3 points

LOW PROBABILITY DVT D-Dimer Neg Positive STOP CUS legs Normal DVT STOP
TREAT

MODERATE PROBABILITY DVT
D-Dimer Neg Positive STOP CUS legs Normal DVT CUS leg in 1 week TREAT Normal Positive STOP TREAT

HIGH PROBABILITY DVT CUS legs Normal DVT Venography TREAT Normal
Positive STOP TREAT

Case 1 Continued Okay back to it… U/S shows popliteal vein DVT
Management Doctor?

Treatment Scarvelis, D. , and P. Wells. 2006
Treatment Scarvelis, D., and P. Wells Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087. Goals: Short Term: Prevent extension of thrombus and/or PE Long Term: Prevent recurrent events Prevent complications Chronic Venous Insufficiency Pain Vericose Veins Ulcers Postphlebitc syndrome Pulmonary Hypertension

Medical Management Rosen’s Emergency Medicine 6th Edition
Used to be  admit  start UFH and Warfarin Now know that LMWH equally efficacious and ?more safe Many centres now go for either tinzaparin (175 U/kg OD) or Enoxaparin (1mg/kg BID) UFH (80U/kg IV bolus then 18U/kg/h infusion) Unless contraindications, can start AC in ED [Warfarin (10mg) Required for at least 3 months] not all cases Goal INR is usually 2-3 The cornerstone of VTE treatment is pharmacologic anticoagulation. Anticoagulants work by inhibiting the clotting cascade and shifting the imbalance back in favor of endogenous fibrinolysis. No randomized controlled trial has ever been performed proving the usefulness of heparin, and it was accepted as standard therapy before the widespread use of current diagnostic modalities. Treatment with either fixed-dosing LMWH or adjusted-dosing unfractionated heparin (UH) is generally acceptable. Benefits of LMWH include easier dosing, no required serial laboratory studies, and easier transition to the outpatient setting potentially decreasing hospital length of stay.

Thrombotic complications (18 trials)
Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism Van 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 A meta-analysis of LMWH versus UH found LMWH more efficacious with significantly less complications including major bleeding events and death, suggesting superiority of LMWH. One major limitation of LMWH is cost. Two studies have now demonstrated that subcutaneous UH can be used alone to treat VTE with similar efficacy and safety as LMWH. Furthermore, Kearon and colleagues validated a safe and effective method of fixed-dosing subcutaneous UH that does not require following activated partial thromboplastin times. Pending further studies, subcutaneous UH may provide a significantly cheaper and promising alternative to LMWH. Aric 2005

Case 1 Continued Pt started on Enoxaparin
Arranged to see her oncologist and a hematologist as out-patient 2 days later

Discharge Scarvelis, D. , and P. Wells. 2006
Discharge Scarvelis, D., and P. Wells Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087. Outpatient treatment is safe and effective in a wide variety of patients Admission may be required if: Co-morbidities: Renal failure, high bleeding risk Extensive DVT (painful blue leg) Necessity for parenteral narcotics Inability to have injections at home

Special Circumstances

Superficial Thrombophlebitis
Uncommonly evolves into a thromboemboic event BUT, many patients have synchronous DVT (~8%) Consider treatment with ASA or LMWH Then symptomatic treatment with: NSAIDS Heat Graded compression stocking (30-40 mmHg) Ambulation Superficial thrombophlebitis in the absence of proximal DVT is not known directly to lead to PE. Approximately 8% of superficial thrombophlebitis can extend into the deep venous system, however, usually at the site of the proximal greater saphenous vein, and potentially embolize to the lung. The main concern in the ED is to rule out superficial thrombophlebitis extension into the deep venous system by ultrasonography. Isolated superficial thrombophlebitis does not require admission, but treatment should be initiated to prevent propagation to deeper veins. Aspirin and LMWH both decrease superficial thrombophlebitis propagation and recurrence with similar efficacy and safety, and either is an acceptable option for superficial thrombophlebitis of the legs. Graded compression stockings, heat pads, and elevation of the affected extremity may help provide symptomatic relief.

How do you want to manage this?
Case 2 44♂, painful swollen right calf Hx/PE: 3/7 days ago – dull ache No trauma/previous DVT Calf swollen 4cm, generally tender No other risk factors U/S: Isolated calf DVT How do you want to manage this?

Isolated Calf or Saphenous DVT Canadian Medical Associan Journal
Rarely causes leg symptoms (80% of symptomatic DVT involve proximal veins) Rarely cause clinical significant PE ~25% of untreated calf DVTs will extend to involve the proximal veins Vast majority of those that will progress do so within a week of presentation Previously, it was believed that isolated calf DVTs did not pose a thromboembolic risk. Longitudinal studies have since shown a 20% to 30% incidence of clot propagation to the proximal venous system with a 20% incidence of embolization. In symptomatic patients, LCUS provides only 73% sensitivity for distal DVTs. High-risk patients with a negative LCUS and positive D-dimer test should undergo repeat ultrasound in 7 days to exclude propagation of a distal clot. In addition to clot propagation and PE, distal DVTs result in postthrombotic complications, such as pain, edema, and hyperpigmentation, in 10% to 38%of patients. Treatment of distal DVT is controversial and either aspirin or low-dose LMWH therapy is currently acceptable. Given the incidence of clot propagation and postthrombotic complications, many clinicians recommend treating distal DVTs the same as proximal DVTs with full anticoagulation therapy. When aspirin therapy is used alone, serial ultrasonography is recommended to ensure lack of propagation to proximal vessels. Clinically this means that you can re-U/S them and hold the LMWH (+/- ASA)

Phlegmasia Cerulea Dolens (Painful Blue Leg)
Massive iliofemoral occlusion results in swelling of the entire leg with extensive vascular congestion and associated venous ischemia Leg is extremely painful and cyanotic Vascular surgery consult If timely consult not available, early thrombolytic therapy maybe limb-salvaging Phlegmasia cerulea dolens is a severe form of DVT in which venous obstruction of the major deep veins and collateral veins leads to a sharp rise in venous pressure, massive interstitial fluid shifts, decreased arterial perfusion, compartment syndrome, and gangrene. Recognition of phlegmasia cerulea dolens is important in the ED for consideration of time sensitive interventions, including anticoagulation, catheter-directed thrombolysis, and vascular surgical consultation

Upper Limb Venous Thromboses Bernardi, E., et al. 2001. Semin Vasc Med. 1;105-10.
Catheter related vs non ALL require treatment High embolization rate If present, central venous catheters should be removed Upper-extremity DVT includes thrombosis in the internal jugular, innominate, subclavian, or axillary veins. It occurs in approximately 16 per 100,000 persons in the United States. Central access devices represent the largest risk factor and are associated with 80% of all upper extremity DVTs. Peripherally inserted central catheters, frequently used for their lower incidence of infectious complications, have a 10% to 40% incidence of upper-extremity DVT. It is unclear why some patients form spontaneous (noncatheter associated) upper-extremity DVTs. An analysis of one large registry found younger age, lower body mass index, non-white race, and smoking to be factors more common in spontaneous upper-extremity DVTs, suggesting this entity has a different pathophysiology from other forms of VTE

What’s new and exciting?

Fondaparinux Matisse 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

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

Other topics for you to think about
Superficial Thrombophlebitis Thrombolysis IVC filters

Pulmonary Embolus (PE)

Background Rosen’s Emergency Medicine: 6th Edition
PE results from a clot that formed hours, days, or weeks earlier in the deep veins which has traveled to the lungs Presentation is highly variable EP’s probably correctly identify about half of pts with PE ~10% of ED pts die within 30 days even with prompt diagnosis If no cardiopulmonary disease, 30% obstruction can be tolerated with minor symptoms only PE occurs when a thrombus breaks free from the endothelial wall, travels through the right side of the heart, and lodges into the narrowing pulmonary arteries. Depending on the size and shape of the clot, it may come to rest in the main pulmonary artery, in a tiny subsegmental artery, or anywhere in between. The shape may allow for normal blood flow or it may obstruct an entire vessel. Minute differences within the vasculature can lead to a myriad of pathophysiologic consequences resulting in a wide range of clinical signs and symptoms.

Case 3 61♀ presents to ED complaining of mild pleuritic chest pain
Total knee arthroplasty 5/12 ago. Healthy otherwise Tell me about: History Physical Investigations

Risk Assessment Emergency 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 Symptoms associated with PE depend on the degree of vascular obstruction, the magnitude of inflammatory response, and the patient’s physiologic reserve. V/Q mismatch manifests as dyspnea, hypoxemia, and increased A-a gradient. Extravasation of blood into alveoli can cause pleuritic pain, cough, or hemoptysis. Increased pulmonary vascular resistance can lead to strain patterns on EKG; pleural effusions; right ventricular dilatation or hypokinesis; or severe right heart outflow obstruction manifesting as hypotension, syncope, or pulseless electrical activity cardiac arrest. It may also manifest as hypoxia if previously closed atrial septal defects open and cause significant transcardiac shunting. The natural history of PE is to present atypically and can include any combination of these findings or none at all.

Risk Assessment Emergency 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 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 Similar to clinical signs and symptoms, most tests used in the ED have poor sensitivity and specificity for PE and are nondiagnostic. Nondiagnostic tests that may be abnormal in PE include electrocardiogram, chest radiograph, arterial blood gas, echocardiography, brain natriuretic peptide, and troponin-T. CXR Often abN (one study says 76%, but the changes are often nonspecific EKG The EKG occasionally reveals manifestations of right heart strain, usually in patients with massive PE. The most common finding in patients with non-massive PE is normal sinus rhythm. In patients with massive PE, anterior T-wave inversions were found more frequently (68%) than sinus tachycardia (28%) or S1Q3T3 (50%). In a population of patients with confirmed PE studied by Kosuge and colleagues, T-wave inversions in both leads V1 and III had 99% specificity. Some authors suggest that the finding of simultaneous T-wave inversions in the anterior and inferior leads should prompt consideration of PE even when it had not been previously suspected.

Bottom Line By themselves, H&P can help to stratify patients
But like w/ DVT, we now have standardized criteria

Pretest Probability Emergency Medicine Reports. 2004;25(11)
All decision trees start here Several exist Wells and Geneva validated Wells NPV: 99.5% Others more cumbersome to use Geneva (Wicki): add ABG, CXR PISA-PED: Add ECG

Case 3 Continued HR: 104 Nil else She gets 1.5 points Now what?
Do you even start to work her up for PE?

Pretest Probability Rosen’s Emergency Medicine. 6th Edition
One approach is to compare pretest prob with the “test threshold” Theoretical cutoff is pretest prob above which some workup should be initiated and below which the pt would be harmed by further testing Test Threshold for PE is ~1.8-2% Canadian (Wells) score <2 had probability of 1.3% but not repeated How then? Unstructured  variable PE Rule Out Criteria  Developed and validated in two populations … To avoid this problem, Kline and colleagues developed the pulmonary embolus rule out criteria rule to identify which low-risk patients do not need D-dimer or other testing, essentially a close to no-risk group. When all eight criteria are present there is less than 2% possibility of PE.

PE Rule-Out Criteria (PERC Rule) Kline, JA. et al. J Thromb Haemost
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 interobserver agreement used to narrow to rule of 8. The PERC criteria have been validated in two separate patient populations.

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

Validation Phase: 2 Groups 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 Very low risk (chief complain dyspnea – PE not suspected) n = 382, 9 (2.4%) had VTE diagnosed within 90d

Endpoint: VTE before 90 days. Good follow-up Both Wells score and PERC rule functioned relatively well Wells better with very low risk population and included more patients in both groups Both had very wide confidence intervals

PERC Rule – Bottom Line Pause before ordering a D-dimer in a patient
Compliments clinical judgement 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

Case 3 Continued Age > 50 HR >100
Does not meet PERC criteria. Wells 1.5  Send the D-dimer Result: 0.59 mg/L (↑) Does this mean anything? What if it was 1.9 mg/L?

D-dimer in PE Does D-dimer level correspond to clot burden in PE?
What about mortality?

D-dimer in PE Grau, E. et al. Crit Care Med. 2007; 35:1937-41
Observational study of 588 pts with symptomatic PE Quantitative D-dimer performed on admission (Automated Latex agglutination test) and clinical follow up for 90 days

D-dimer in PE Grau, E. et al. Crit Care Med. 2007; 35:1937-41
= mg/L Compared to pts with D-dimer ng/mL, OR of 90d mortality: 1.91 (0.91 – 4.09) in pts with D-dimer 2.94 (1.42 – 6.45) in pts with D-dimer ≥ 5000 Pts with D-Dimer ≥ 5000 ng/mL: Higher risk of death from fatal pulmonary embolism OR 4.4 (0.5-33) than from other causes OR 2.1 ( ) 95% CIs for odds ratios cross 1 More of a point of interest = mg/L = ≥ 5 mg/L

Confirmatory Testing Evaluation divided between screening and confirmatory testing “Screening” is H&P, D-dimer Confirmatory: Gold Standard ?still Angiography Landmark Articles used: V/Q [Pioped I] CTPA [Pioped II] MRA [Pioped III]

PIOPED I – V/Q Scanning PIOPED Investigators. JAMA. 1990;263:2753
Multicentre study Sens/Spec of V/Q in setting of pre-test prob Reference standard was Angio/autopsy Before single and MDR-CT, the V/Q scan was the first-line imaging modality for PE. It is a nuclear imaging test that assesses for areas of ventilation without perfusion as evidence of PE. Scan results include normal, low probability, intermediate probability, or high probability.

The appropriate interpretation of results depends on assessment of pretest probability. Here, a high probability scan was 96% accurate when the clinical probability was high, but only 56% accurate when clinical probability was low. Furthermore, 57% of patients with PE had low- or intermediate-probability V/Q scans.

Most important finding was that PE often present in non-diagnostic scans w/ high clinical probability Except in low probability pts, low probability scans require additional testing CT or repeated Dupplex U/S (Rosen’s) Because of frequent indeterminate results, V/Q scans do not affect management 40% to 60% of the time, making it a less popular test in the ED. A normal chest radiograph increases the likelihood of a diagnostic V/Q scan, whereas patients with abnormal chest radiographs have diagnostic scintigraphy only 9% of the time in one report. Still, the V/Q scan is useful and needed in a subset of patients with a contraindication to CT. Data from PIOPED II are more promising for V/Q scan than PIOPED I, finding a determinate result of ‘‘PE’’ or ‘‘no PE’’ in 77.4% of patients.

PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
Prospective multicentre study, N = 824 Looking at the accuracy of CTA/CTV in setting of clinical prediction tool (Wells) Composite reference standard (incl V/Q, Angio neg U/S) CTA Report 51/824 inconclusive (6%) CTA Sens 83%, Spec 96% CTA-CTV inconclusive 87/824 CTA-CTV 90% and 95% Mostly 4-slice CT (didn’t have enough 8 & 16 slice to comment)

PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
Data from PIOPED II shows that CTA follows the rules of Bayes’ theorem similarly to other diagnostic tests in VTE. That is to say that the positive and negative predictive values of CTA are affected by the pretest probability of disease. A negative CTA is more likely a true-negative in the low-risk group, and a positive CTA is most likely a true-positive in the high-risk group. In high-risk patients, the NPV is a disappointing 60%. In this group, the addition of CTV to CTA augments the NPV to 82% and is recommended by the PIOPED study group.

Didn’t really give us the answers that we wanted
PIOPED II – Bottom Line Lalani, N. Don’t Feed Me BS and Call it Candy. 2006 Didn’t really give us the answers that we wanted Didn’t enroll 2/3 of eligible pts CT Scanners have evolved since Compared with V/Q, reports are far more ‘binary’ CT is probably better than this  The weakness of CTA is its poor ability to detect small peripheral PEs. Further interpretation of this data as well as those from other studies go into this further, but in the interest of time, we’ll move on. Many of these studies bring on the question of whether these additional subsegmental PEs found on MDR-CTA are clinically relevant. No study has demonstrated safety in withholding anticoagulation to patients with diagnosed isolated subsegmental PEs, but some authors liken them to distal DVTs that do not necessarily warrant full anticoagulation. Given the dynamic balance of fibrin formation and breakdown in the body, some believe that one of the natural functions of the lung vasculature is to filter the blood and prevent clots from traveling to other end-organs. Others believe, however, that diagnosis of subsegmental PE is evidence of a prothrombotic state and increased risk for further VTE.

Dutch study 510 pts all got spiral CT +/- U/S
Gold standard: 90d follow-up False Neg Rate 0.4%, Sens 99.6% 8/510 scans indeterminate  angio

Multi-detector Row CT Stork, A. Knows Too Much for Own Good. 2005
4,8,16, 64 row scanners Resolution <1mm Visualization to 6th order vessels Entire chest scanned in <10seconds Reduce number of non-diagnostic scans Less intravenous contrast Can be formatted to 2D and 3D images Result Increased sensitivity for subsegmental PE

8-bit vs 64-bit resolution

CT vs Angiography Wlner-Muram, HT. et al. Radiology
Prospective study of 93 pts (emerg and ward) in whom PE was suspected 4-slice CT and pulmonary angiography within 48h SN: 100% SP: 89% Limitations: Not huge numbers Had 3 independent reviews of all studies

Outcomes: Multi-detector Row CT Moores, L. , et al. Ann Intern Med
Meta-analysis of 23 studies Negative CT PE who didn’t receive AC 4657 patients Results (3 month follow up) VTE: 1.4% ( %) Fatal PE: 0.51% ( %) Conclusions CTPA has similar rates of recurrence as angiography Appears safe to withhold anticoagulation based on negative CTPA

Outcomes: Multi-detector Row CT Quiroz, R. , et al. JAMA
15 Studies Reviewed, N=3500 Studies excluded: D-Dimer used as initial triage tool Insufficient F/U (needed at least 3 months) Poor quality study (objective criteria) NPV: 99.1% ( ) NLR: (0.05 – 0.11)

CTPE Quick Widely available Relatively non-invasive
Performs similarly to angiography Provides a “binary” outcome (interpreter dependent) Can offer alternative diagnosis when PE is absent

CTPE - Weaknesses Poor ability to detect small, peripheral PE’s
?Clinically relavence Protocol variability (slices, legs, venogram included) Interpretation variability (day/night, staff/resident) Radiation Contrast (anaphylactoid reactions, nephropathy) Pts may have contraindications The weakness of CTA is its poor ability to detect small peripheral PEs. Further interpretation of this data as well as those from other studies go into this further, but in the interest of time, we’ll move on. Many of these studies bring on the question of whether these additional subsegmental PEs found on MDR-CTA are clinically relevant. No study has demonstrated safety in withholding anticoagulation to patients with diagnosed isolated subsegmental PEs, but some authors liken them to distal DVTs that do not necessarily warrant full anticoagulation. Given the dynamic balance of fibrin formation and breakdown in the body, some believe that one of the natural functions of the lung vasculature is to filter the blood and prevent clots from traveling to other end-organs. Others believe, however, that diagnosis of subsegmental PE is evidence of a prothrombotic state and increased risk for further VTE.

CT Scanning: Bottom Line
CTPA should be considered as good as the gold standard When used with DD and U/S, NPV of >95%

Magnetic Resonance Angiography Fields, JM, & Goyal, M
Magnetic Resonance Angiography Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: Advantages: Eliminates radiation Probably safer in pregnancy Decreased nephrotoxicity Disadvantages: Cost Availability Failure to demonstrate adequate SN in preliminary studies MRA provides another diagnostic choice in PE diagnosis. Multiple MRA techniques exist with varying degrees of accuracy. The most common is gadolinium-enhanced MRA, which accurately identifies proximal clots,but poorly detects subsegmental emboli. One study found a sensitivity of 77% and specificity of 98% of gadolinium-enhanced MRA for PE. Recently, MR perfusion scanning was developed, which uses signals from gadolinium to estimate blood volume in regions of the lung. Identification of decreased blood volume represents indirect evidence of PE. Although studies are few, one study found a sensitivity and specificity of 100% and 91%, respectively, when perfusion MRI was compared with MDR-CTA. Role still needs to be defined – my take: don’t hold your breath! (Sorry, bad joke)

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

Real-Life Aproach Fields, JM, & Goyal, M. Venothromboembolism
Real-Life Aproach Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: There is some debate to the use of D-dimer in the intermediate probability group. Although some studies have demonstrated that a single D-dimer may safely be used in the intermediate-risk group, the clinician must be aware that the posttest probability from a negative D-dimer in this group was still 5% (assuming a pretest probability of 30% and a NLR of 0.1) *Prevalence rates of PE for each pretest probability group based on multiple clinical prediction rules

CHR Approach Again, the next 4 slides describe the current Calgary Health Region approach Even fewer people use this than the DVT model: Released before PIOPED II (CTPE not included) V/Q results don’t tend to be this straightforward

Wells Criteria for Probability of PE
Clinical Hx/Sign Criteria Points 1. S/S of DVT leg swelling – objectively measured AND pain with palpation in the deep vein region 3.0 2. Pulse>100/min 1.5 3. Immobilization bedrest (except access to BR) > 3 days OR surgery in previous 4 weeks 4. Previous DVT or PE Must have been objectively diagnosed 5. Hemoptysis 1.0 6. Malignancy receiving active treatment for cancer OR have received treatment for cancer in past 6 mo. OR are receiving palliative care for cancer 7. PE as likely or more likely than an alternative Dx. No specific criteria – use Hx, Physical, CXR, EKG, and labs to decide Total Points Probability LR < LOW MODERATE > HIGH

LOW PROBABILITY PE: D-Dimer Neg Positive STOP VQ Scan Normal Non-high
CUS legs Pulm Angio Normal DVT Normal Positive CUS In 1 week TREAT STOP TREAT

MODERATE PROBABILITY PE:
D-Dimer Neg Positive STOP VQ Scan Normal Non-high High CUS legs TREAT Normal DVT Pulm Angio CUS In 1 week TREAT OR

HIGH PROBABILITY PE: VQ Scan Normal Non-high High Pulm Angio OR
CUS legs OR Pulm Angio TREAT Normal DVT Pulm Angio OR CUS In 1 week TREAT

What does the expert say. Wells, PS. J Thromb Haemost
What does the expert say? Wells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50 Divide pts into PE likely (Wells >4) or unlikely (≤4)

Case 3 Continued Recall… Low probability (Wells 1.5) D-Dimer: Positive
Therefore... CTPE  Positive

Treatment Emergency Medicine Reports. 2004;25(12)
First decide primary therapy Significant clot burden  immediate removal Chemical - thrombolysis Mechanical – embolectomy Less Significant Anticoagulation UFH, LMWH, Coumadin Next decide prevention against future emboli Anticoagulation IVC filters On diagnosis or high suspicion of PE, rapid initiation of therapy can be lifesaving. Treatment with either UH or LMWH is acceptable and the principles are similar to treatment of DVT. When PE is strongly suspected (ie, high probability), initiation of heparin therapy before radiologic confirmation likely provides more benefit than risk. Clots can enlarge at an exponential rate. Furthermore, normotensive patients who die from PE do so within the first 24 hours, underscoring the importance of rapid assessment and treatment. In patients with PE and an absolute contraindication to anticoagulation or patients already on full anticoagulation, an emergent inferior vena cava filter should be considered.

Fibrinolysis Ramakrishnan, N
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) Fibrinolytics rapidly dissolve clot by active breakdown of fibrin, but they are nonselective and can cause severe bleeding. Fibrinolysis involves the administration of recombinant or bacterial tissue plasminogen activators that increase circulating plasmin and accelerate fibrin breakdown. Their use is generally recommended for massive PE with hemodynamic instability where the risk of bleeding is overshadowed by the potential benefits, but the benefit is unclear. Multiple case reports and small case series suggest potential improved outcomes and return of spontaneous circulation following fibrinolytic administration In a study by Kucher and colleagues fibrinolytic therapy did not decrease 90-day mortality or recurrence of PE in patients with massive PE. The data are equally as unimpressive in patients with submassive PE. Still, fibrinolysis should be considered in patients who show signs of clinical deterioration with worsening respiratory distress or hypotension because PE-related cardiac arrest has a dismal prognosis.

Fibrinolysis in sub-massive PE Ramakrishnan, N
Fibrinolysis in sub-massive PE Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4) In the NEJM paper, the primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter. When you separate out the important clinical outcomes….this is what you see – obviously not as impressive! 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.]

Fibrinolytics – Bottom Line
Consider in PE with hypotension or systemic hypoperfusion or in the rapidly deteriorating patient I’m not going to present any data specifically on massive PE, but basically, if they’re going down the tubes, consider lytics. With respect to embolectomy, in patients with massive PE refractory to fibrinolysis, surgical embolectomy performs better than repeat fibrinolysis. Embolectomy provides a reasonable and potentially lifesaving final therapeutic pathway in massive PE. When successful, patients have excellent long-term results.

Out-Patient Treatment of PE Merli, GC. et al
Out-Patient Treatment of PE Merli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi: Is it technically possible? Newer treatments allow out-pt treatment of VTE LMWH SC UFH 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)

V. Low Risk = 1.1% 30d Mortality 
The Geneva Risk Score (Table 4) is a clinical scoring system that has undergone both internal and external validation. The Geneva Risk Score was developed using multi-variate analysis of clinical factors present at the time of admission in 296 consecutive patients with pulmonary embolism. During the 3 month follow-up, 2.2% (4 of 180) of low risk patients (a score <2) experienced an adverse clinical outcome, including death, recurrent thromboembolism, or bleeding, compared with 26% in the high-risk patients (score of >3). Aujesky et al developed and validated the pulmonary embolism severity index to classify patients with acute pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. In this study of 15,531 inpatients discharged with pulmonary embolism from 186 Pennsylvania hospitals, 11 factors were found to be independently associated with 30 day mortality. The risk class specific mortality varied from 1.1% in Risk Class I to 24.5% in Risk Class V. V. Low Risk = 1.1% 30d Mortality 

Out-Patient Treatment of PE Merli, GC. et al
Out-Patient Treatment of PE Merli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi: 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 So, Is it technically possible to treat somebody at home? Yes Can it be safe? In the right, low-risk patients – probably Now you need to look at your patient and decide if it’s appropriate to treat them out of hospital. That requires consideration of their other medical conditions and their unique social factors

There is no consensus on who can safely be treated at home
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.

Wait, is she just a little hefty or…?
Common – VTE most frequent cause of death in pregnancy / 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 VTE is the most frequent cause of death in pregnancy with the highest risk in the postpartum period. As with non-pregnant patients, symptoms and signs of VTE can be highly variable. Because many trials exclude pregnant patients, questions arise as to the correct usage of diagnostic testing in this population. Use of D-dimer testing in pregnancy is controversial. As in non-pregnant patients, D-dimer tests provide good sensitivity, but specificity decreases as gestational age increases. Lower specificity means more false positives and more patients needing imaging. When signs of DVT are present, ultrasound is the recommended diagnostic strategy because it poses no known risk to the fetus. When PE is suspected, presence of DVT clinches the diagnosis, but when symptoms of DVT are absent, ultrasound is rarely positive. What about CTPE or V/Q?

Average fetal radiation dose with helical CT is less than that with
PE in Pregnancy Winer-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 Study used US to determine fetal geometry Monte Carlo method for measuring radiation dose of helical CT 2.5mm cuts to 4cm below xiphoid Previously, V/Q scan was recommended over CTA as the initial diagnostic study for PE in pregnant patients because of decreased radiation exposure. Newer-age CT scanners have significantly less radiation delivered to the fetus to near equal or even lower doses of radiation from V/Q scanning. Fetal radiation dose from lung scanning is approximately 100–370 Gy, which is apparently a relatively low exposure. For helical CT, estimated mean fetal doses in micrograys at varying gestational ages were as follows: 3.3–20.2 Gy, first trimester; 7.9–76.7 Gy, second trimester; and 51.3–130.8 Gy, third trimester 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.

PE in Pregnancy Cook JV, Kyriou J
PE in Pregnancy Cook 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/ risk of Ca by age 15) V/Q: 0.12 mGy (1/ ) Breast absorbed doses: CTPE: 10 mGy V/Q: 0.28 mGy Less risk to fetus, more to mom (particularly breast Ca) Pregnant women with a family history of breast cancer or who have had previous computed tomography for pulmonary angiography may wish to elect for lung perfusion scans, despite the slightly higher risk to the fetus. CTPE: less risk to fetus, more to mom’s breasts

PE in Pregnancy - Treatment
Same as other populations except Warfarin Known Teratogen  don’t use.

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 All upper limb DVT require treatment CTPE is very powerful when combined with DD, U/S If neg – safe to withhold treatment

PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

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PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

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