Tag Archives: PE

IVC Filters: Another Nail In The Coffin?

IVC filter insertion has been one of our tools for preventing pulmonary embolism for decades. Or so we thought. Its popularity has swung back and forth over the years, and has been in the waning stage now quite some time. This pendulum like motion offers an opportunity to study effectiveness when coupled with some of the large datasets that are now available to us.

IVC filters have been used in two ways: prophylactically in patients at high risk for pulmonary embolism (PE) who cannot be anticoagulated for some reason, and therapeutically once a patient has already suffered one. Over the years, guidelines have changed, and have frequently been in conflict. Currently, the American College of Chest Physicians does not recommend IVC filters in trauma patients, while the Eastern Association for the Surgery of Trauma promote their use in certain subsets.

A Pennsylvania group performed a large, retrospective review of three databases, the  Pennsylvania Trauma Outcome Study (462K patients), the National Trauma Data Bank (5.8M patients), and the National Inpatient Sample. All were patients with an emergent trauma-related admission.

Here are the most interesting factoids:

  • About 2% of all patients underwent IVC filter insertion, and 94% were inserted prophylactically
  • About 90% of patients with a prophylactic filter had at least one predictor for PE, which means that the remaining 10% had none (!)
  • Conversely, about 86% of patients who developed a PE had at least one risk factor, meaning that 14% had no recognized risk factors (!!)
  • The use of IVC filters peaked in 2006-2008 at 2-4%, then falling steadily over the following 5-7 years to less than 1%
  • PE rates peaked in 2008, then declined by 30% in the PTOS sample and stayed steady in the NTDB

Bottom line: The use of IVC filters peaked in 2008 and has been in decline since then. But interestingly, the rates of PE and fatal PE have been steady to declining, depending on the data set. Obviously, there are always some shortcomings for studies like this. Remember, IVC filters are intended to prevent fatal PE. It is possible that some fatal PEs were not identified in these databases. Furthermore, it was not possible to obtain any information on the use of chemical prophylaxis in these patients. 

Overall, there has been no increase in PE and fatal PE rates over the time period that IVC filter usage has been decreasing. This suggests that these devices have not had their intended effect. Trauma professionals need to very seriously consider the specific indications in any patient they are considering for insertion. They may not have the protective effect you think.

Related posts:

Reference: Vena Cava Filter Use in Trauma and Rates of Pulmonary Embolism, 2003-2015. JAMA Surg 152(8):724-732, 2017.

Is Fine-Tuning Lovenox Dosage Using Anti-Factor Xa Worthwhile?

Deep venous thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are major concerns in all hospitalized patients. A whole infrastructure has been developed to stratify risk, monitor for the presence of, and provide prophylactic and/or therapeutic drugs for treatment. But if you critically look at the literature from the past 20 years or so, we have not made much progress.

One of the newer additions to our arsenal has been to figure a way to determine the “optimal” dose of enoxaparin. Three options are now available: weight-based dosing, confirmation by thormboelastography (TEG), and anti-factor Xa assay. Let’s look at another paper that focuses on the last item.

Anti-factor Xa levels provide a way to monitor low molecular weight heparin activity. A number of papers published have sought to determine a level that predicts adequate activity. Although they are not of the greatest size or quality, a range of 0.2-0.4 IU/ml seems to be the consensus.

A large number of patients at a busy Level I trauma center were retrospectively studied to see if achieving a peak anti-factor Xa level of at least 0.2 IU/ml would result in less VTE. All patients were started on enoxaparin 30mg SQ bid within 48 hours of admission. Anti-factor Xa was measured 4 hours after the third dose. If the level was less than 0.2 IU/ml, the dose was increased by 10mg per dose. The cycle was repeated until anti-factor Xa was therapeutic.

Here are the factoids:

  •  All patients with a Greenfield Risk Assessment Profile (RAP) of 10 or more (high risk) were included; duplex ultrasound surveillance for lower extremity DVT was performed weekly
  • 194 patients were included, with an average RAP of 9 and ISS of 23 (hurt!)
  • Overall VTE rate was 7.4%, with 10 DVT and 5 PE (!)
  • Median time to diagnosis was 14 days
  • Initial anti-factor Xa levels were therapeutic in only one third of patients, and another 20% reached it after dose increases. 47% never achieved the desired level, even on 60mg bid dosing.
  • There was no difference in DVT, PE, or VTE rates in patients who did vs did not achieve the goal anti-factor Xa level
  • Injury severity and obesity correlated with inability to reach the desired anti-factor Xa level

Bottom line: In this study, achieving or not achieving the goal anti-factor Xa level made no difference whether the patient developed VTE or not. And it was difficult to achieve anyway; only about half ever made it to the desired level. How can this happen?

Well, there are still many things we don’t understand about the genesis of VTE. There are probably genetic factors in every patient that modify their propensity to develop it after trauma. And there are certainly additional mechanisms at play which we do not yet understand. 

For now, we will continue to struggle, adhering to our existing protocols until we can figure out the real reason(s) VTE happens, the best ways to prevent, and the best methods to treat.

Related posts:

Reference: Relation of Antifactor-Xa peak levels and venous thromboembolism after trauma. J Trauma accepted for publication Aug 2, 2017.

Aspirin For DVT Prophylaxis In Trauma

The use of mechanical and pharmacologic prophylaxis for prevention of deep venous thrombosis (DVT) and venous thromboembolism (VTE) in trauma patients is nearly universal. However, no matter how closely we adhere to existing guidelines, some patients will develop these conditions. Indeed, about 80% of patient who suffer some type of VTE event were receiving prophylaxis at the time.

Trauma is a major factor in causing hypercoagulability. Although current chemoprophylaxis focuses on clotting factors, platelets play a big part in the clot formation process. Our usual drugs, though (various flavors of heparin), have no effect on them.

What about adding aspirin to the regimen? My orthopedic colleagues have been requesting this for years. There is a reasonable amount of data in their literature that it is effect in patients with knee arthroplasty only. As usual, it is misguided to try to generalize management based on experience from one specific body region or operation.

A single Level I trauma center reviewed its data on aspirin prophylaxis for trauma patients. They reviewed their registry data from 2006 to 2011. They identified 172 trauma patients with duplex ultrasound proven DVT. These patients were matched with 1,901 control patients who underwent at least one duplex and never developed DVT. Matching was performed carefully to ensure that age, probability of death, number of DVT risk factors, and presence of TBI were similar. The total number of matched patients studied was 110.

And here are the factoids:

  • About 7% of patients with DVT were on aspirin at the time of their injury, vs 14% of the matched controls
  • 7% were taking warfarin, and 4% were taking clopidogrel
  • Analysis showed that patients taking aspirin had a significantly decreased chance of DVT after injury
  • On further analysis, it was found that this effect was only significant if some form of heparin was given for prophylaxis as well.

Bottom line: So before you run off and start giving your patients aspirin, think about what this study really said. Patients taking aspirin before their injury and coupled with heparin after their injury have a lower rate of DVT. It gives us no guidance as to whether adding aspirin after the fact, or using aspirin alone, are useful.  And we still don’t know if any of this decreases pulmonary embolism or mortality rates.

Related posts:

Reference: Aspirin as added prophylaxis for deep vein thrombosis in trauma: a retrospective case-control study. J Trauma 80(4):625-30, 2016.

Enoxaparin And anti-Xa Levels: Who Cares? Part 3

Today is the final installment in a series about the use of anti-Factor Xa levels to titrate enoxaparin dosing to prevent venous thromboembolism (VTE). This is another study that tries to show that “hitting the number” actually makes a difference in patient care. You decide.

This study identified a subset of patients at high-risk for VTE based on a commonly used and very good risk screening tool, the Risk Assessment Profile (RAP). It takes some 17 factors into account to arrive at a numerical score. In this paper, the authors chose a score of 10 or greater to denote high risk. The patients were all seriously injured, and were in the trauma ICU of this established Level I trauma center.

This retrospective study excluded non-ICU patients, ones who did not receive enoxaparin or anti-Xa levels, and two patients with DVT on admission. This brought the number of eligible patients from 621 to 127 (the treatment group). They then narrowed the field down to the high-risk treatment group by excluding patients with a RAP score < 10. Now we are down to 86. But then 30 more (35%) were excluded because they did not undergo duplex ultrasound screening, leaving only 56 to study (!).

The control group was a “similar” historical cohort from a two year period from 2009 to 2012. You can tell that this group is getting a little stale, because the only patients included were those who received unfractionated heparin for prophylaxis (remember those days?). Of the 106 patients in the control group, 20 (28%) were reported as have VTE. However, it included 6 patients with DVT on admission, which were excluded in the study group. This makes the DVT rate look higher in the control group. It also included 2 upper extremity DVT and 1 septic pelvic venous thrombosis. Excluding all of these brings the historical VTE rate down to only 10%. Remember this.

So let’s get on to the factoids:

  • Only 35% of the 127 patient treatment group “hit the number” for anti-Xa (0.2-0.4 IU/ml) after three 30mg doses of enoxaparin
  • An additional 25% managed to achieve the desired anti-Xa level after dose adjustment, but 51 patients (40%) never did get there
  • There were 10 VTE events in the 127 treatment group patients, 9 of whom had high RAP scores, giving them a 7.8% rate of VTE
  • Nine of the 10 VTE patients occurred in patients with low anti-Xa levels
  • The authors compared their 7.1% DVT rate with the 21% in their historical controls, concluding that titrating anti-Xa levels reduced this rate. They did not include PE for some reason, and do not claim a statistical difference. They admit that the study was underpowered to detect differences in VTE. There is no significant difference in VTE rates in the study or control groups.

Bottom line: This is the last paper on the topic. I promise. At least for a while. Here’s what we know:

  • VTE is a problem in trauma patients, particularly seriously injured ones
  • We are not very good at sticking to a prophylaxis or screening regimen (note how many patients are excluded in all of these studies)
  • We can’t seem to generate the numbers to conduct a good study that can detect differences in what we do
  • It’s difficult to “hit the number” for anti-Xa using standard enoxaparin dosing
  • We don’t even know if it makes a difference if we do “hit the number”. VTE rates seem to be the same regardless.

So we are struggling to make a lab test look right to adjust enoxaparin dosing, and we don’t even know if it makes a difference. Will somebody put a good, multi-center study together and help us to figure all of this out?

Related posts:

Reference: Anti-Xa-guided enoxaparin thromboprophylaxis reduces rate of deep venous thromboembolism in high-risk trauma patients. J Trauma 81(6):1101-1108, 2016.

Enoxaparin And anti-Xa Levels: Who Cares? Part 1.5

Oops, I’ve got to backtrack a little. I just ran across a newly published study from the authors mentioned in Part 1 of this series a few days back. I pointed out some of the issues that surfaced as they tried to “hit the numbers” for factor anti-Xa levels in patients from their hospital. Here’s a breakdown of the new study.

First, I love the beginning of the title:

“If some is good, more is better”

Really?

Recognizing that 30% of patients had low anti-Xa trough levels when given the standard 30mg bid dosing regimen for enoxaparin, the authors engaged in some fancy predictive and statistical models to come up with a new one. A good portion of the methods section of the paper is devoted to explaining the machinations of exactly how they did this.

They used a patient dataset that was a little fresher than from Part 1. Three years of data from 2011 to 2014 were reviewed, and 275 patients were used to generate the new models. They selected one of seven candidates, based on a combination of simplicity and fewer supranormal levels of anti-Xa. They used this model to guide dosing to the next 145 patients. Here is the new regimen:

Weight Dose (q 12 hrs)
50-60 kg 30 mg
61-99 kg 40 mg
> 100 kg 50 mg

And here are the factoids:

  • Of the 275 patients used to create the model, 70% were subtherapeutic. (This is exactly the same number as in the first paper, but a different number of patients. Hmm.)
  • With the new dosing regimen in place, only 21% were subtherapeutic
  • Patients with supratherapeutic anti-Xa levels increased from 2 to 5% using the new routine
  • VTE was the same, at about 3-4%
  • Four patients developed VTE on the new regimen, and 3 of them had therapeutic anti-Xa levels (!)

Bottom line: A lot of modeling and statistical work went into the production of this paper. I still wonder why the number of patients included over 3 years is so low for such a busy center. But the authors certainly showed that they could improve the rate at which they “hit the number.” But how important is this, really?

The concluding sentence of the abstract reads, “further studies are needed to determine whether such dosing decreases venous thromboembolism rates.” Perhaps we should figure that out before continuing to spend lots of time playing with dosing changes and blood tests.

Reference: If some is good, more is better: an enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis. J Trauma 81(6):1095-1100, 2016.