Tag Archives: VTE

Abstracts, Pharmacy

Best of AAST #1: Aspirin Vs Low Molecular Weight Heparin For VTE Prophylaxis

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The 82nd Annual Meeting of the American Association for the Surgery of Trauma begins next week. As is my custom, I will be reviewing some of the more interesting (to me) oral presentation abstracts until the last day of the meeting.

When reading abstracts, keep in mind that you are seeing just a snippet of a finished manuscript. The authors are given very little print space to fully describe their research idea, their methods, and their results’ significance. Sometimes, what is seen in the abstract varies significantly from what is actually heard at the meeting. But mercifully, this does not happen often. The abstract is usually an intriguing look at some new and exciting work.

Having said all that, an abstract should not be a reason to change your practice! It is usually early work and needs to be fully vetted at peer review. Even then, it needs to be taken in context with past, similar research before trickling down to patient care.

The first abstract is fascinating. Our orthopedic surgery colleagues have been trying to use aspirin for venous thromboembolism (VTE) prophylaxis for decades. Frequently, they are thwarted by the trauma surgeons, who are thoroughly indoctrinated in the low molecular weight heparin (LMWH) camp.

This work comes from the Shock Trauma Center in Baltimore and is a follow on to a paper published in the New England Journal of Medicine earlier this year. The paper demonstrates that aspirin is not inferior to LMWH when used for VTE prophylaxis of patients. There was no difference in death from all causes, VTE occurrence, wound complications, or bleeding events.

The abstract is a follow-on to that manuscript. The authors performed a secondary analysis of the initial data to see if aspirin provided the same apparent level of protection in patients with high risk for VTE as measured by the Caprini score.

Here are the factoids:

  • A total of 12,211 patients were enrolled in this multi-center, and the same outcomes listed above were monitored for 90 days
  • Of the total group, 3052 were judged to be high risk: 46% had a femur fracture, 42% had a pelvic/acetabular fracture, 48% had a thoracic injury, 39% had a spinal injury, and 35% had a head injury
  • There was no difference in death, deep venous thrombosis, pulmonary embolism, or bleeding in the two groups
  • Patient-reported satisfaction was significantly better by 68% in the aspirin group

The authors concluded that outcomes for aspirin vs. LMWH are similar, even in patients at high risk for VTE.

Bottom line: This is an intriguing abstract, pointing me to the original paper published in NEJM. This multi-center study was performed in conjunction with the research coordinating center at Johns Hopkins, which designs some top-notch research. This study was no exception.

I am fascinated with this work because it shows that our orthopedic colleagues were right! They’ve been trying to get us to use aspirin for a long time. It’s very cheap compared to LMWH, by a ratio of about 50,000:1. 

If you’ve followed me for a long time, you would know I have been skeptical of the VTE prophylaxis establishment. Looking historically at its evolution over the last 40+ years, the incidence of DVT and fatal PE have changed very little despite the introduction of heparin, low molecular weight heparin, and anti Factor Xa monitoring. But it’s been established practice, so we’ve had to abide by the rules. Now, a cheaper alternative to all of this is being shown to be just as (in)effective. 

I suspect that if others bear out this work, we will be able to use a cheaper prophylaxis drug that does not require injection. But we still need to work on figuring out the basis for this problem to hopefully reduce it to near zero someday.

References: 

  • Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopaedic trauma patients. AAST 2023 Plenary Paper 3.
  • Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med 2023; 388:203-213.
Complications

Predicting VTE Risk In Children

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There’s a lot of debate about if and at what age injured children develop significant risk for venous thromboembolism (VTE). In the adult world, it’s a little more clear cut, and nearly every patient gets some type of prophylactic device or drug. Kids, we’re not so certain about at all.

The Children’s Hospital of Wisconsin tried to tease out these factors to develop and implement a practice guideline for pediatric VTE prophylaxis. They prospectively reviewed over 4000 pediatric patients admitted over a 6 year period.

It looks like the guideline was developed using some or all of this data, then tested using regression models to determine which factors were significant. The guideline was then tweaked and a final model was implemented.

Here are the factoids:

  • 588 of the patients (14%) were admitted to the ICU, and 199 of these were identified as high-risk by the guidelines
  • Median age was 10 (this is always important in these studies)
  • VTE occurred in 4% of the ICU patients, and 10% of the high-risk ones
  • Significant risk factors included presence of central venous catheter, use of inotropes, immobilization, and GCS < 9

Bottom line: This abstract confuses me. How were the guidelines developed? What were they, exactly? And the results seem to pertain to the ICU patients only. What about the non-ICU kids? The abstract just can’t convey enough information to do the study justice. Hopefully, the oral presentation will explain all.

I prefer a very nice analysis done at the Oregon Health Science University in Portland. I wrote about this study earlier this year. The authors developed a very useful calculator that includes most of the risk factors in this model, and a few more. Input the specific risks, and out comes a nice score. The only issue is, what is the score threshold to begin prophylaxis and monitoring? Much more practical (and understandable) than this abstract. Check it out at the link below.

References:

  1. Evaluation of guidelines for injured children at high risk for venous thromboembolism: A prospective observational study. J Trauma Acute Care Surg. 2017 May;82(5):836-844.
  2. A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients. JAMA Surg 151(1):50-57, 2016.
Abstracts, Complications, Head

Best Of EAST 2023 #12: VTE Prophylaxis In Severe TBI

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Time for another abstract on venous thromboembolic disease (VTE) prophylaxis, but this time in patients with severe head injury. VTE is a significant problem for trauma patients. Those with a potential source of bleeding from their injuries cause us to hesitate and consider the timing of chemical prophylaxis closely. Do we really want to cause more bleeding?

This is particularly problematic with intracranial hemorrhage, as the treatment is major brain surgery. Over recent years, the literature has been leaning toward earlier prophylaxis as soon as the intracranial blood has stopped evolving.

The EAST Multicenter Trials Group performed a seven-year retrospective review at 24 Level I and II trauma centers to assess the safety and efficacy of VTE chemoprophylaxis.  They divided patients into three groups: no prophylaxis, early prophylaxis (within 24 hours), and late prophylaxis (after 24 hours).

The authors assessed two endpoints: VTE occurrence and expansion of intracranial hemorrhage (ICH). They used several regression models to check their hypotheses.

Here are the factoids:

  • A total of 2,659 patients met the inclusion criteria. This averages out to 15 eligible patients per month per center. This is probably reasonable when combining a few high-volume centers with more lower volume centers.
  • Compared to early prophylaxis, patients who received late prophylaxis were twice as likely to develop VTE, although this was not statistically significant (p = 0.059)
  • Compared to early prophylaxis, patients who received no prophylaxis were a third less likely to develop VTE, although this, too, was not statistically significant (p = 0.39
  • About 25% of patients who received either early or late prophylaxis suffered an extension of their ICH, but only 17% of the no-prophylaxis group did
  • The regression model showed that the no prophylaxis group was 36% less likely to develop ICH extension compared to either early or late prophylaxis groups.

The workgroup concluded that the development of VTE was not dependent on the timing of the start of prophylaxis. Furthermore, patients who did not receive any prophylaxis had significantly decreased odds of ICH extension. The group recommended larger randomized studies to extend this work.

Bottom line: Shocker! This multicenter study suggests that the no prophylaxis and early prophylaxis groups had fewer VTE events than the late group, although these results were not statistically significant. This means that there wasn’t an advantage to giving the shot.

And the other major conclusion was that both early and late prophylaxis was associated with a significantly higher incidence of ICH extension. 

Roll these together, and you will find that neither early nor late prophylaxis help prevent VTE, yet they are both associated with additional bleeding in and around the brain! 

Heresy! I am trying to figure out what to make of these results. Perhaps the retrospective nature of the study and the wildcards this introduces influenced the results. It could be a study power problem, except the numbers were approaching significance that was unfavorable for prophylaxis.

I will be very interested to hear how the authors explain these findings. And yes, a well-powered randomized study would be great, but I don’t think many institutional review boards will be keen on a no-treatment group given our current fear of VTE. So don’t count on any real answers soon.

Reference: EARLY VTE PROPHYLAXIS IN SEVERE TRAUMATIC BRAIN INJURY: A PROPENSITY SCORE WEIGHTED EAST MULTICENTER TRIAL. EAST 2023 Podium paper #38.

Abstracts, Pharmacy, Solid organ

Best Of EAST 2023 #10: Early VTE Prophylaxis In Adolescents With Solid Organ Injury

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Chemoprophylaxis against venous thromboembolism (VTE) is routine in trauma care. In most cases, it can be initiated shortly after admission in most trauma patients. However, there are a few major exceptions, including eye injuries and brain injuries with intracranial hemorrhage.

Solid organ injury used to be cause for concern when considering prophylaxis, but most trauma centers are now comfortable beginning within 24 to 48 hours after injury. Having said that, those numbers are for adult patients. What about the younger ones?

The University of California Irvine group queried the TQIP database (3 recent years) to examine outcomes for adolescent patients (12-17 years old) given VTE prophylaxis after injury to liver, spleen, and/or kidney. They excluded patients who had TBI, anticoagulation or coagulopathy, immediate laparotomy, transfers in, and patients who died or were discharged within 48 hours. They matched patients for age, comorbidities, grade of injury, overall severity of injury, and hypotension/need for transfusion.

Eligible patients who received chemoprophylaxis early  (within 48 hours) vs. late were reviewed to identify any differences in complications, length of stay, failed non-op management, and mortality.

Here are the factoids:

  • A total of 1,022 cases were isolated from the TQIP database, and 417 adolescent cases were matched to adults
  • VTE rate was statistically the same, 0.6% in the early group vs. 1.7% in the delayed group
  • Failed non-op management was identical at 5.9% vs. 5.6%
  • There was one death in the delayed group and none in the early group (not significant)
  • ICU LOS was the same at 3-4 days
  • One item not mentioned in the body of the abstract: hospital length of stay was significantly longer in the early group: 9 days vs. 6 days

The authors concluded that early VTE prophylaxis in adolescent trauma patients did not increase failure of nonoperative management, nor did it decrease the incidence of VTE.

Bottom line: This is a study that needed to be done. Due to IRB restrictions, it is typically more challenging to perform actual studies on children and adolescents. Retrospective use of databases helps overcome this problem, although it always introduces a few unwanted wrinkles.

We frequently assume that adolescents behave physiologically like adults. Although often true, you can’t always count on it. Those of us who take care of children and young adults know that they tend to do better than adults by most measures. But again, this is an assumption and needed to be studied.

This database study was limited to three years of data and only produced 417 matched cases for study. This is a small number, and I always worry about statistical power. If the results of such a study are negative, one is left wondering if a proper power analysis was done.

One puzzling result left me wondering about the power question. Patients who received early prophylaxis had exactly the same rate of VTE as those who received it late. Adult data indicates that early use should decrease this complication. Is this another indication of a statistical power problem? Would the inclusion of more patients have shown a real difference?

The other result that struck me (and was not commented upon in the body of the abstract) was the statistically significant 50% increase in hospital length of stay for the early prophylaxis group. Is there some unknown variable that was not matched that caused it? This is one of the known pitfalls of these retrospective database studies.

Here are my questions and comments for the presenter/authors:

  • Broken record question: Did you have enough cases to provide adequate statistical power? This study showed a negative result. Did you have enough matched cases to actually be able to detect a difference if there was one? Why not add a few more years of data and recalculate?
  • How do you explain the failure of early VTE prophylaxis to protect these patients from DVT or PE? Is this also a statistical power problem?
  • Why is the hospital length of stay significantly longer in the early prophylaxis group?

This intriguing paper follows my bias toward treating these patients exactly the same as adults with early chemoprophylaxis. I just need a few of the loose ends tied up.

Reference: SIMILAR RATE OF VENOUS THROMBOEMBOLISM AND FAILURE OF NON-OPERATIVE MANAGEMENT FOR EARLY VERSUS DELAYED VTE CHEMOPROPHYLAXIS IN ADOLESCENT BLUNT SOLID ORGAN INJURIES: A PROPENSITY-MATCHED ANALYSIS. EAST 2023 Podium paper #27.

Abstracts, Prevention

Best of AAST 2022 #3: VTE Risk After Spinal Cord Injury

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Venous thromboembolism (VTE) is always a concern in trauma patients. But patients with spine fractures are at much higher risk and those with spinal cord injuries on top of it even more so. The best tool we have right now for prevention is chemoprophylaxis with some type of heparin. Unfortunately, VTE prophylaxis is commonly interrupted or delayed due to concern for causing bleeding. These concerns may relate to concomitant injuries (e.g. solid organ injury) or necessary surgical procedures.

About five years ago, the Army provided a $4.25M grant to fund the Coalition of Leaders in Thromboembolism (CLOTT) study group. It involved contributions from 17 Level I trauma centers attempting to look at the incidence, treatment, and prevention of VTE after trauma. Additional phases are now under way to look at offshoot discoveries from the original research.

A group from the University of California – Sand Diego performed a secondary analysis of a subset of the CLOTT study in patients age 18-40 over a three year period. Patients with a diagnosis of spinal cord injury who were admitted for at least 48 hours were analyzed. The authors focused on timing of the start of VTE prophylaxis, VTE rates, and missed prophylactic dosing. They also reviewed any bleeding complications.

Here are the factoids:

  • From the entire CLOTT study group, 343 met criteria and had sustained a spinal cord injury
  • Most subjects were young (mean 29) and male (77%) and had sustained blunt injury (79%)
  • A total of 44 patients (13%) developed VTE – 30 DVT, 3 pulmonary embolism, and 11 pulmonary thrombus
  • Only one in five patients started chemo-prophylaxis prior to 24 hours, and this increased to about 50% at 48 hours (!)
  • VTE rate overall was 9.6% (?)
  • The rate trended lower in patients who received their prophylaxis within 48 hours (7% vs 13% but not significant)
  • Missed doses of chemo-prophylaxis were common (30%) and were associated with higher VTE rates

The authors concluded that VTE rates are high in these patients and early chemoprophylaxis is critical in limiting thrombotic events.

Bottom line: Hmm. This abstract confuses me a little. Actually, I had expected a higher VTE rate in this patient group. I’ve seen reports 2x to 3x higher than reported here. But yes, I do believe that these patients are at high risk.

And looking at the chart, it appears that there is a trend toward higher rates in patients who missed doses rather than those who did not. But the real questions are:

  1. Is it real? That is, are those differences significant? The only analysis in the abstract compares early vs late administration and that is trending toward significance but didn’t quite make it there. And remember that the graph you are looking at cuts off at 18% which makes the differences look much bigger.
  2. What can we do about it? Many trauma professionals are still uncomfortable giving prophylaxis early because of fear of bleeding. This is probably unwarranted, but we just don’t have enough hard data to say so. Anecdotal data about surgeons operating uneventfully through chemoprophylaxis is growing, though.

My impression of this study is that it shows some interesting trends, but probably doesn’t include enough subjects to know the real answer for sure. 

Here are my questions for the authors / presenter:

  1. Tell us about the statistics. How did you calculate the rates that are cited in the paper? I can’t figure out the math.
  2. What is the difference between a pulmonary embolism and pulmonary thrombus? Is it merely the presence or absence of concomitant clot in the legs or pelvis? Why distinguish between the two if you are lumping them all together as “VTE?”
  3. What are we to do with this data? Obviously, everyone wants to provide VTE prophylaxis in a timely manner. But there are a raft of reasons why clinicians are “not comfortable” doing it. Any suggestions?

Reference: VENOUS THROMBOEMBOLISM RISK AFTER SPINAL CORD INJURY: A SECONDARY ANALYSIS OF THE CLOTT STUDY. Plenary Paper 23, AAST 2022.