Testing for DVT/PE Steve Kizer MD

Why do the strategies for testing for thromboembolic disease seem so difficult? Confusion as to the goals of treatment Poor understanding of the tests Confusion by proxy

The goals of therapy By far, most patients presenting with PE are stable. For those that are critical, attention is directed to removing the embolus. But for nearly all patients, our goal is to prevent a second PE with little regard to the existing PE. In some series, 60% of those presenting with DVT will already have a PE at the time of presentation.

The Goals of therapy, (cont’d) If we can show that the deep venous system is empty, or becomes empty, then PE will not recur. (Hull & Hirsch, 1997) Calf vein thrombi (below the popliteal space) are not a cause of PE and are a risk factor for PE only if they extend proximally. Most pelvic disease will also propagate distally. In a patient suspected of PE, studies of the proximal veins are often negative because the clot has moved.

The goals of therapy, (cont’d) Therefore the goal of therapy is straightforward: If the deep venous system is empty in a patient diagnosed with PE, then we treat to assure that the venous system remains empty. If there is clot in the deep venous system, then we treat to assure that extension and embolization of existing clot is minimized. Thus, DVT and PE are the same disease.

Goals of treatment (cont’d) How certain does one have to be that a patient has DVT/PE before undertaking treatment? 90%? 60%? 30%? 10%?

The notion of thresholds There are four decision nodes for treating any disease. What happens if I DON’T treat someone with the disease? What happens if I DO treat someone with the disease? What happens if I DO treat someone who does not have the disease? What happens if I DON’T treat someone who does not have the disease?

What happens if I don’t treat someone with the disease? 10% die. Quality adjustment 0, value = 0 30% complication (SOB, post-phlebitic leg,etc) Quality adj. 0.9, value = % alive and well. QA 1.0, value = 0.6 Total quality adjusted survival 0.87 for this decision

What happens if I treat someone with the disease? Dead 0.5%, Quality adjst 0, value = 0 Complications 12% (bleeds, post-phlebitic leg, SOB, etc.) QA 0.9, value = 0.11 Alive and well 87.5%, QA 1, value = Total survival value for this decision. NET benefit of treatment – 0.87 = 0.116

What happens if I treat someone who does not have the disease? Dead 0.05%, QA 0, value = 0 Complications 5% (minor, major bleeds, etc) QA 0.9, value = Alive and well, 94.9% QA 1, value Total quality adjusted survival value of this decision = 0.994

What happens if I don’t’ treat someone and they don’t have the disease? This is the perfect decision Dead 0%, QA 0, value = 0 Complications 0%, QA 0.9, value = 0 Alive and well, 100%, QA 1.0, value = 1 Total value of this decision = 1.00 Thus, harm of treating patients who don’t have the disease 1.00 – = 0.006

Finally, the threshold Threshold defined as ratio of harm to benefit. Total harm = Total benefit = Harm/benefit (this is an odds) = 0.006/0.116 Harm/benefit (probability) = 0.006/0.122 = 0.05 or 5%. This means if the patient that I am caring for has a greater than 5% chance of DVT/PE when all is said and done, then I treat!

Now, understanding the tests Why do we test? To increase or diminish the probability of disease In many cases we test sequentially, but this demands that the tests perform independently - an unproven assumption in most cases. Nevertheless, we can probaby come close to the truth with such an assumption in DVT/PE since the tests are unrelated physiologically.

The tests Multiple slice CT (corrected for indeterminate scans) +LR 7.8 -LR 0.2 V/Q scan High prob LR 17.8, Indeterminate 1.0, Normal or near normal 0.10 D-dimer (high sens and depends on cut-off) + LR 2.4 -LR 0.10 (only useful in outpatients!!!) Compression US (symptomatic pts) +LR 24 –LR 0.06

Using the tests The purpose of testing is to get above or below the treatment threshold This requires knowing the test characteristics as in the two previous slides and: Estimating pretest probability of PE/DVT.

Well’s Rule for Pretest probability of PE, applied when the clinical complaint may be PE. Previous DVT 1.5 pts Recent hosp/leg trauma 1.5 pts Pulse > pts Clinical evidence of DVT 3 pts No other reasonable Dx 3 pts Malignancy 1 pt Hemoptysis 1 pt For a score less <1 Prob <5%, %, 7+ 70%.

Well’s rules for Pretest probability of DVT, when presenting complaint may be DVT. * May not be fully valid in primary care. Recent casting/hemiparesis 1 pt Recent surgery/hospitalization 1 pt Malignancy 1 pt Calf circumference > 3cm diff 1 pt Swelling of leg by measurement 1 pt Unilateral edema 1 pt Past hx of DVT 1 pt Unilateral swelling superficial veins 1 pt Tenderness along the venous system 1 pt Another equally likely dx -2 pts 0 or less 5% prob of DVT, %, 3+ 50%.

Using the tests. SJ 32 yo healthy woman presents to clinic with pleuritic chest pain, no fever, cough. No trauma. Exam is normal, HR 97. CXR wnl. Pretest Prob? (score?) ~30% Prob (no other dx) What test to order?

Patient SJ – Can we decrease the Probability? Pretest Prob 30%, odds 3/7 Neg D-dimer 3/7 x 0.10 = 0.30/7 odds Post test prob = 0.3/7.3 = ~5% V/Q scan (normal or near normal) 3/7 x 0.10 = 0.3/7 odds Post test prob = 0.3/7.3 = 0.04 ~ 4% Multislice CT 3/7 x 0.2 = 0.6/7 odds Post test prob = 0.6/7.6 = ~ 8% What would you order?

Pt SJ – Can we increase the probability? D-dimer 3/7 x 2.4 = 7.2/7odds Post test prob 7.2/14.2 = 0.5 ~50% V/Q scan (high prob) 3/7 x 17.8 = 53.4/7 odds Post test prob 53.4/60.4 = 0.88 = ~ 88% Multislice CT 3/7 x 7.8 = 23.4/7 odds Post test prob 23.4/30.4 = 0.77 ~77%

Unanswered questions Can patient with high probability of PE be left untreated if deep venous system is, and remains, empty by US? This has been verified as a viable strategy for those at intermediate probabilities. If so this changes strategy dramatically. Then approach to patients with PE would be to verify empty proximal veins.

Patient RJ 56 yo man, recent MVA, frx of left tibia, casted, also in hospital for 2 wks for ruptured spleen and kidney. Develops SOB, fever, HR 115. CXR clear, U/A wnl, no evidence for abdominal infection. Left leg swollen. Rt calf 31 cm left 34 cm Pretest prob? Score 4, 60% probability

Testing RJ Pretest prob is so high, that our goal is to try to reduce probability to level not requiring treatment (5%). If we cannot, then we treat. D-dimer (not useful in inpatients) V/Q (normal/near normal) 7/3 x 0.1 = 0.7/3 odds Post test prob 0.7/3.7 = 0.19 = ~19% Multislice CT 7/3 x 0.2 = 1.4/3 odds Post test prob 1.4/4.4 = 0.32 = ~32% Now what?

Thinking further about RJ Pretest probability for DVT for RJ, Wells score is 4, ~50% prob of DVT. Duplex US positive 1/1 x 25 = 25/1 odds of DVT or post test prob of 25/26 = 0.97 or 97% prob > Treat Duplex US negative 1/1 x 0.04 = 0.04/1 odds of DVT or post test prob of 0.04/1.04 = or ~4%. > No treatment. Repeat US in 1-2 weeks

Further thinking about RJ This is based on empirical trials of Hull and Hirsch that show for intermediate probability PE if the deep venous system is empty, the risk for PE (even if patient may have had one) is less than 2%.

What have we learned? Possibly nothing Make a reasonable estimate of pretest probability of disease. Then based on your knowledge of the 4 available tests, try to obtain a post test probability less than 5%. If you can, do not treat. If you cannot, then treat.

One final point The threshold will change depending on treatment risks. For example, as the risks of bleeding or complications of therapy increase, the threshold will rise. This means, if a 90 yr old man with a hx of GI bleeding 5 yrs ago is considered, the threshold may go up to 12% or more.

One final, final point Filters, removable or not are not particularly effective or durable treatments for preventing PE. If the filter cannot be removed, the risk for long term complications such as DVT of lower extremities is about 30-35% and after 9mos – 1 year, any protection afforded by the filter wanes.