Extended Thromboprophylaxis in Medically Ill Patients - Episode 5

Role of Biomarkers, Lifestyle Modifications, and LMWH at Discharge

December 12, 2019

Deepak Bhatt, MD, MPH: Is there a role for biomarkers in this sort of risk stratification? Patients made it to hospital, they discharge. Why not just check a D-dimer? If it’s totally normal, probably won’t be, but if it were?

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: The D-dimer has some predictive value, and Mike has done some nice seminal work on incorporating it into a clinical score. I don’t think it’s as useful as being incorporated into a clinical model like IMPROVE. The weight of D-dimer to be predictive of VTE [venous thromboembolism] is I would say in the moderate range or intermediate range. So it’s not as strongly weighted as let’s say a prior history of VTE. I think a combination of a D-dimer embedded into a clinical risk score is the way to go. To be honest, I don’t think we’re quite ready yet for a case finding strategy using screening, ultrasonography. We’ve seen that especially surgical patient populations, having failed multiple times. I really think a pound of prevention is worth an ounce of cure at this point.

Where we’re really dropping the ball in US health systems is saying, well, now that you finished your 3-or 4-day length of stay, you’re good, and you’re discharged home and you don’t need anything. I think the next critical step in my view is formalizing what Gary said, at admission in the discharge planning process. We should formalize VTE risk assessment, not just at admission, but at discharge. If patients continue to have high VTE risk features, either give them an extra week of anticoagulants or if they’re higher risk than that, maybe they would be candidates for extended prophylaxis. That’s the paradigm shift that we’re talking about.

Gregory Piazza, MD, MS: I would echo that. It’s really a struggle to get systematic assessment of VTE risk on admission. But when it’s done it’s terrific. The next frontier is to get it done at the time of discharge, which very few guidelines call for and very few clinicians actually do. For some of these patients, the risk score is not going to change or it may even be worse.

Deepak Bhatt, MD, MPH: Let’s say we’ve made it through discharge, the patient is ready to go. What advice can we give them in terms of lifestyle, should they exercise, assuming they can? Should they get up every couple of hours if they’re watching TV [television]? If it’s a flight we say get up every couple of hours. Should they do that at home? Should someone massage their calves? What exactly are the practical things that we can tell them?

Gregory Piazza, MD, MS: I think a push for early mobility is something that we can all agree is important. There’s a tendency to recommend to patients to take it easy, bed rest, and we want to do the opposite of that. We want to encourage mobility. We want to encourage return to some semblance of regular daily activity, as long as they’re capable of doing it. We know, as Alex said, immobility is, no matter what analysis, what subset of data you look at, immobility always comes up as very predictive.

Deepak Bhatt, MD, MPH: But specifically, what practical advice would you give someone? Someone who’s had a sternotomy, for example, you might say take the incentive spirometer home if it’s a really early discharge. Do it every couple of hours. What do you recommend practically to patients? Of course, some of it’s titrated to their ability to ambulate and just how good shape they are or aren’t in. Do you have any tips or tricks in terms of what you say?

Gregory Piazza, MD, MS: Staying hydrated. More recently we’ve understood that dehydration can increase the risk of VTE 2-fold in some studies.

Deepak Bhatt, MD, MPH: Probably something that’s operative on long distance flights as well.

Gregory Piazza, MD, MS: Right.

Deepak Bhatt, MD, MPH: Drinking coffee, alcohol, or not drinking at all.

Gregory Piazza, MD, MS: Exactly. That’s actually what people think may be the key factor in that. And as I’ve mentioned, get moving, those are 2 lifestyle things that can be helpful.

Deepak Bhatt, MD, MPH: Yes, that’s good stuff.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: What I was going to say actually, in a quarter of your patients, the answer might be simply take your direct oral anticoagulant.

Gregory Piazza, MD, MS: That’s right.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: The one issue in the post-discharge phase is that we’ve only had parenteral options. Trying to tell an 80-year-old female patient with rheumatic disease who can barely hold a pen to actually self-inject for the next 2 weeks was an exercise in futility. I think the beauty now and the paradigm shift that we’ve seen with the trials that we’ll be discussing is the fact now that we have oral-only options. We can give these oral agents not just during their hospitalization but in the post-hospital discharge period. The business of prophylaxis from the patient point of view becomes a lot easier.

Deepak Bhatt, MD, MPH: Since you’ve taken us there, let’s go there. When the patient’s at discharge, we’ve given that lifestyle advice. What are going to discharge the patient on? What is the anticoagulant? You’ve already said you don’t favor parenteral anticoagulation at that point, low molecular weight heparin and so forth. What would you all recommend and what do the data show?

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: I guess I’ll start because everyone is looking at me. I’m not sure why.

Deepak Bhatt, MD, MPH: I was trying to go down the lifestyle route, but then you brought up medicine, so it’s on you.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: You’re absolutely right. I think the 1 thing that we can tell is, yes, if the patients are at risk, they can always have an option to take low molecular weight heparin. Very few of these patients do take it. Number 2) We do have a prior trial using extended low molecular weight heparin, the EXCLAIM trial, with enoxaparin 40 mg once daily. It was a difficult trial. It was actually a pioneer trial, and I really take my hat off to the investigators to have pioneered the way, a difficult trial to do with respect to finding the kind of the real at-risk population. Even that trial suggested that patients who were elderly, had immobility, and were female, may be these key subgroups. That pioneered the way. I think more importantly now, we have positive trials from both the APEX trial that Michael headed, as well as the MAGELLAN and MARINER trials that Gary and I headed and others that show us, in key subgroups of these populations, one could give extended prophylaxis with rivaroxaban.

Deepak Bhatt, MD, MPH: I want to talk about the data from all 3 trials, but just before leaving low molecular weight heparin here, what about if the patient has a history of cancer, does that influence anything in terms of low molecular weight heparin versus going to an oral agent, as you were otherwise endorsing?

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: It’s an interesting paradigm, isn’t it? Because if they’re a cancer outpatient, all of a sudden now the data are really pointing to the way that there’s a subset of these cancer outpatients that would benefit from either low molecular weight heparin in the past but more importantly from a direct oral anticoagulant. These data really don’t apply to the hospitalized cancer patient population, simply because these patients tended to clot but also bleed. So we don’t have the right benefit-risk balance I think in that particular population.

Deepak Bhatt, MD, MPH: I’m glad you made that distinction. It’s a little bit subtle. What about aspirin, any role for aspirin here before we get into oral anticoagulants? Does anyone?

Gary Raskob, PhD: Not for VTE prevention.

Gregory Piazza, MD, MS: Not really in the medical patient.

Deepak Bhatt, MD, MPH: So nobody is a taker for aspirin.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: A lot of head-shaking. That’s pretty unanimous.

Transcript edited for clarity.