Symptoms compatible with DVT followed by PE: A case study

Dr Mark Crowther is a professor and chair of the Department of Medicine and the Leo Pharma Chair in Thromboembolism Research at McMaster University.

A 23-year-old woman with an ovarian cyst treated with oral contraceptives develops lower limb edema 3 months after starting treatment. A diagnosis of deep vein thrombosis (DVT) is established based solely on a D-dimer level >50,000 microg/L. The patient receives low-molecular-weight heparin (LMWH) and is sent home. After a few hours she develops pulmonary embolism (PE).

In a local survey 20% of Polish physicians said they start their diagnostic workup of DVT with D-dimer evaluation. Could you comment on that? Should such patients be admitted for treatment?

Mark Crowther, MD, MSc: It is a great clinical question. I will just make a couple of comments about the case. The first is, the patient presents with clinical symptoms compatible with DVT, but the D-dimer by itself cannot establish the diagnosis of DVT. That person could have a bleed into their leg, which would cause leg pain, swelling, and an elevated D-dimer. They could have osteomyelitis of their leg that would cause swelling and an elevated D-dimer. They could have a fracture. There are many things that can cause both an elevated D-dimer and compatible symptoms.

In the world that we live in we have easy access to ultrasound, so if a patient has an episode of suspected DVT, there is a couple of different strategies you should follow. Again, I would refer the listener to look at the recently published American Society of Hematology guidelines because there is an entire chapter on diagnostic approaches to venous thromboembolism (VTE).

The way that we would approach that patient is we would do a history and physical examination and based on an established scoring system, such as the Wells score, we would establish a pretest probability of VTE. If the pretest probability was low, which it will not be in this case because of the clinical presentation, then a D-dimer that is normal and a low pretest probability rule out the diagnosis and further testing is not required.

But essentially, in all other circumstances, a D-dimer is actually not required. If a patient shows up with leg pain and swelling that is compatible with DVT, a D-dimer does not meaningfully inform your care of the patient. They need to have an ultrasound done. And if you do not have ultrasounds immediately available, you need to figure out the way of getting them.

People make the assumption that the bigger the thrombus, the more serious it is. There is not really evidence for that. The larger the thrombus is, the higher the likelihood of postthrombotic syndrome (PTS). That is real. But there is no evidence that the risk of, for example, PE is affected by the size of the clot.

We frequently get calls that say, “The person has a giant clot extending into their iliac.” We would treat them exactly the same as we would treat someone else because I am not aware of evidence that the extent of the clot predicts acute complication rates. It does probably predict PTS but not acutely. And I am certainly not aware of any indication that the extent of the initial clot should dictate treatment strategies.

There is no evidence I am aware of that the extent of DVT should dictate treatment strategies. We treat all deep vein thrombi—unless the patient has another complicating factor—at home. We would not ever admit a DVT unless the patient had another reason to be in the hospital. We are very confident in the use of therapeutic doses of direct oral anticoagulants as an outpatient to treat acute DVT. I am not aware—there may be, but I am not aware—of any scoring systems that suggest that certain characteristics of a DVT of the leg should predict need for hospitalization.

For PE, the story is a little bit different. There are validated scoring systems for PE that suggest that there is a group of patients who can be safely treated at home and a group of patients who should be admitted to the hospital. If the patient has certain risk characteristics—you can look at the different scoring systems—then that person should probably be admitted to the hospital for PE. But, again, a large fraction of patients with PE can be safely treated at home and can be safely treated with apixaban, rivaroxaban in a way that we would treat anybody else with rivaroxaban or apixaban. There is a strong hesitation because people believe that coming in to the hospital is somehow better for the patient, but in fact there is no evidence for that; it increases health-care costs. And, you know, my hospital had a bad Clostridioides difficile problem in the past. You do not want to admit people to the hospital unless they really need to be in the hospital.

The question of whether or not a patient should be admitted to the hospital and, in this particular case, the fact that she came back shortly with a PE… We know that about a half of patients who present with acute proximal DVT will have a PE if you do screening and they do not have symptoms; and we know that about more than 90% will have a PE if they have any symptoms.

We would always make the assumption that a patient with a DVT has a PE. The treatment is exactly the same. I would be very comfortable sending her home. We would tell her about the signs and symptoms of PE and to come back for an evaluation. If she had symptoms of PE like some chest pain and shortness of breath but was otherwise well, we would probably send her home again with her PE.

The key, though, is not to think that because she had an event 3 hours later, she had a failure of rivaroxaban. She did not. It is just the natural history of the disease.