Category Archives: Complications

Best Of EAST #9: Is TXA Associated With VTE?

Most trauma programs can be divided into two types: those that believe in tranexamic acid (TXA) and those that don’t. I won’t get into the details of the CRASH-2 study here. But those centers that don’t believe usually give one of two reasons: they don’t think it works or they think the risk of venous thromboembolism (VTE) is too high.

EAST put together a multi-institutional trial to see if there was an association between TXA administration and subsequent VTE. The results are being reported as one of the paper presentations at the meeting this week. A retrospective study of the experience of 15 trauma centers was organized. A power analysis was preformed in advance, which showed that at least 830 patients were needed to detect a positive result.

Adult patients who received more than 5 units of blood during the first 24 hours were included. There were a lot of exclusionary criteria. They included death within 24 hours, pregnancy, pre-injury use of anticoagulants, interhospital transfer, TXA administration after 3 hours, and asymptomatic patients that had duplex VTE surveillance (huh?). The primary outcome studied was incidence of VTE, and secondary outcomes were MI, stroke, length of stay, and death.

Here are the factoids:

  • There were 1,333 eligible patients identified, and 887 (67%) received TXA
  • Females were significantly (over 2x) more likely to receive TXA (46% vs 19%)
  • 80% of patients given TXA received VTE prophylaxis, whereas only 60% of those who did not receive TXA got prophylaxis (also significant)
  • TXA patients had a statistically significantly higher ISS (27) compared to non-TXA patients (25) but this is not clinically significant
  • Mortality in the TXA group was significantly lower (17% vs 34%)
  • The number of units of blood, plasma, and platelets transfused were significantly lower in the TXA group
  • VTE rate appeared lower in the TXA group, but once multivariate analysis was applied, there was no difference

The group concluded that there was no association between TXA and VTE, but that it was linked to decreased mortality and transfusion need.

My comment: This was a study done the way they are supposed to be! Know your objectives and study outcomes up front. Figure out how many patients are needed to tease out any differences. And use understandable statistics to do so.

But, of course, it’s not perfect. No retrospective study is. Nor is any multi-institutional trial. There are lots of little variations and biases that can creep in. But the larger than required sample size helps with reducing the noise from these issues.

Basically, we have a decent study that shows that the clinical end points that we usually strive for are significantly improved in patients who have TXA administered. We don’t know why, we just know that it’s a pretty good association.

This study shows that the usual reasons given for not using TXA don’t appear to hold true. So hopefully it will convert a few of the TXA non-believers out there. I’m excited to hear more details during the presentation at the meeting.

Reference: Association of TXA with venous thromboembolism in bleeding trauma patients: an EAST multicenter study. EAST Annual Assembly, Paper #13, 2020.

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Best Of EAST #8: Early vs Late Full Anticoagulation In TBI

Trauma professionals are always reluctant to anticoagulate TBI patients with demonstrated blood in their head. In recent years, we’ve become more comfortable providing prophylactic doses of low molecular weight heparin after a suitable period. This is typically 24-48 hours after a stable head CT in patients with select types of intracranial hemorrhage (ICH) who are at increased risk for venous thromboembolism.

But what about therapeutic dose anticoagulation in these patients? Let’s say that you have a patient with ICH who has developed a significant pulmonary embolism (PE)? Is is safe to give full dose anticoagulation? And if so, when?

The group at Shock Trauma in Baltimore attempted to answer this in one of the EAST Quick Shot presentations scheduled for this week. The did a retrospective review of 4.5 years of their own data on these patients. They specifically selected patients who had both ICH and PE and compared those who received full anticoagulation within 7 days of injury vs those who were dosed after 7 days. Outcomes studied included death, interventions for worsening ICH, and pulmonary complications.

Here are the factoids:

  • A total of 50 patients had both ICH and PE, but only the 46 who received therapeutic anticoagulation were analyzed
  • 19 patients (41%) received early anticoagulation, and 27 received it late (59%)
  • There were 4 deaths in the early group (2 from the PE, 1 from multi-system organ failure, 1 from the TBI) vs none in the late group, and this was statistically significant
  • 3 patients in the early group (18%) vs 2 in the late group (7%) had an increase in their ICH (p=0.3), and none required intervention

The authors concluded that their study failed to show any instances of clinically significant progression of ICH after anticoagulation, and that it is not associated with worse outcomes, even if started early. Thus they recommend that ICH should not preclude full anticoagulation, even early after injury.

My comment: I always say that you shouldn’t let one paper change your practice. Even a really good one. In order to ensure that you are providing the best care, more work must always be done to confirm (or refute) the findings of any provocative research. And this little Quick Shot, with little opportunity for questions from the audience, should definitely not change it!

The major issues to consider here are common ones: 

  • This was a retrospective study and it does not appear that any guideline was followed to determine who got early vs late anticoagulation. So who knows what kind of selection bias was occurring and how the surgeon decided to prescribe anticoagulation? It’s very possible that patients with a “bad CT” were put into the late group, and the not so bad ones in the early group. This would bias the results toward better outcomes in the early anticoagulation group.
  • It’s also a very small study that is extremely underpowered. The authors comment on the fact that the outcomes of the early group were not worse than the late group. However, looking at their sample size (46) shows that they would only be able to show differences if they were about 5x worse in the early group. They would realistically need about 350 total patients to truly show that the groups behaved the same. Their small numbers also preclude saying that there were no ICH progressions. There very well could have been if 300 more patients were added to the series.
  • And isn’t death a significant outcome? The authors indicated that 2 of the 4 deaths were a result of the PE. Yet there was a significant association (p=0.02) of increased death in the early anticoagulation patients that can’t be discounted.

Bottom line: It’s way too early to consider giving early anticoagulation to patients with ICH and pulmonary embolism. It may very well be shown to be acceptable, eventually. But not yet. And a much bigger prospective study will be required to confirm it.

Reference: Therapeutic anticoagulation in patients with traumatic brain injuries and pulmonary emboli. EAST Annual Assembly Quick Shot #7, 2020.

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Best Of EAST #7: Is There A Relationship Between Number Of Transfusions And Infection?

It has long been known that blood transfusion decreases immunocompetency for a period of time. This has been taken advantage of in transplant surgery for decades. And blood transfusions are used liberally in major trauma. So could blood transfusion make it more likely for a trauma patient to suffer complications such as pneumonia, sepsis, and surgical site infections?

The group at the Massachusetts General Hospital explored this possibility. The analyzed four years of TQIP data, examining patients who received blood transfusions within four hours of arrival. They excluded transfers in, patients with incomplete transfusion counts, and those who died within 48 hours.

They focused on pneumonia, sepsis, and surgical site infections and statistically controlled for demographics, comorbidities, injury severity, and surgical/procedural interventions.

Here are the factoids:

  • A million patients (!) were reviewed and about 41,000 met study criteria
  • The odds ratio of infectious complications increased from 1.23 after 2 units to 4.89 after 40 units
  • Each additional unit after 40 increased the odds of an infection by another 4.9%

The authors concluded that blood transfusion is associated with a dose dependent risk of infectious complications and that patients should be resuscitated to achieve prompt hemorrhage control (really?).

My comment: Well, this certainly looks fairly straightforward. Of course, it suffers from the usual drawbacks of massaging large databases. And remember, it shows an association, not cause and effect. How can we tease out whether the higher infection risk is due to badly hurt patients who need major surgery and prolonged ICU stays with pneumonia? The authors have tried to reduce this as much as possible using logistic regression. Unfortunately, many of the variables are very interdependent and I don’t believe the methods can fully overcome this. And there may be other factors not available for analysis in the TQIP data.

Here is my only question for the authors and presenter:

    • How can you be sure that you have fully controlled for the key variables that might influence your final analysis? Yes, you considered demographics, three listed comorbidities (cirrhosis, diabetes, and steroid use), injury severity, and some interventions. But might there be other factors not listed and maybe not even in the TQIP data? Ideas?

This is one of those papers that makes you say “hmm”. But don’t we always try to stop the bleeding promptly. I’m not sure what alternative we have to giving blood.

Reference: Overtransfusion comes at a significant cost: the dose-dependent relationship between blood transfusions and infections after major trauma. EAST Annual Assembly abstract #26, 2020.

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Best Of EAST #4: Cannabis And Venous Thromboembolism

Cannabis and cannabidiol (CBD) are all over the news these days. CBD is legal everywhere, and it seems that more states are legalizing cannabis every few months. There are a few hints in PubMed that cannabinoids (THC) may have some impact on clotting, possibly causing hypercoagulability.

The group at the University of Arizona in Tucson decided to look into this in trauma patients. They did a two year scan of the TQIP database and stratified patients based on their THC status. They matched up THC positive and negative patients and examined thromboembolic events (deep venous thrombosis, pulmonary embolism, stroke, MI) and mortality.

Here are the factoids:

  • Nearly 600,000 patients records were in the database pull, but only 226 patients were THC+
  • They were matched at a 1:2 ratio with similar THC – patients (452)
  • No differences were found in the usual demographics, injury severity, use of DVT prophylaxis, and hospital length of stay
  • The THC+ group had a significantly higher incidence of overal thromboembolic complications (9% vs 3%)
  • Both DVT ( 7% vs 2%) and PE (2.2% vs 0.2%) were significantly higher in the THC+ group
  • No differences were seen in strokes or MI

The authors concluded that THC increases the risk of DVT and PE and that early identification and treatment for thromboembolic complications is required to improve outcomes in this high risk subset of trauma patients.

My comment: Seems compelling, right? But this is one of those abstracts that you have to read really closely. You have two groups of patients that are being compared, and a few statistical differences were found. The groups are small, but even so these differences are great enough to reach statistical significance. Great!

But, now step back and look carefully at the larger patient group. There are almost 600,000 patients there, but am I to believe that only 226 patients (0.04%) were using cannabis? According to recent statistics, approximately 8% of the US population currently uses marijuana. So in theory, about 47,500 patients in the TQIP sample should have tested positive. For whatever reason, this data point was not collected. Could data from the other 47,274 have changed the study result? Probably. 

Here are my questions for the authors and presenter:

  1. What was the impetus for this study? I was not aware of clotting issues due to THC and there is little in the published literature. I’d love to hear some history and be able to read more about this.
  2. What about the long time interval that a patient will test THC+ after partaking? THC remains in body fat for a month or more, and the qualitative test commonly used will provide a positive for weeks after the last use. How long do the thrombogenic effects of THC last? The THC+ result recorded in the dataset could be from THC use well before the traumatic event.
  3. How do you think your small sample of THC+ patients impacts your results given the much larger number of expected marijuana users in the sample?

This is intriguing work. Let’s here more!

Reference: Impact of marijuana on venous thromboembolic events: cannabinoids cause clots in trauma patients. EAST Annual Assembly abstract #4, 2020.

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Best Of EAST 2020 #1: Treatment Of Blunt Carotid & Vertebral Injuries

The 33rd Annual Assembly of the Eastern Association for the Surgery of Trauma starts in just two weeks! As usual, I will select several interesting abstracts from the bunch to review. I’ll go over the findings of the research, critique it, and then provide a series of questions for the presenter to consider. These questions are ones that members of the audience may very well ask (hint, hint).

And FYI, I always send a heads-up to the presenters with a link to the post so they can study up beforehand!

So let’s get started with the first abstract that will be kicking off the meeting on January 15. Blunt cerebral / vertebral artery injury (BCVI) is one of those insidious injuries that trauma professionals don’t always think about. But they do occur in about 1% of major trauma patients. It’s one of those injuries that can’t be ignored because very serious complications may occur if it is not treated appropriately (think stroke).

Unless there are extenuating circumstances like bleeding or pseudoaneurysm, treatment is usually pharmaceutical. There are two camps: antiplatelet drugs vs anticoagulant drugs. But there is very little data to determine which one is better.

This abstract is a retrospective review from the National Readmission Database (NRD). This resource is maintained by the US government and provides information on patient readmissions nationally across all payors as well as the uninsured. They included all patients > 18 years old with a BCVI and minor injuries in other body regions. Patients who suffered a stroke complication during their initial hospital stay were excluded.

Patients were divided into two groups: those taking an antiplatelet agent and those prescribed an anticoagulant. Outcomes of interest were readmission with CVA and death, within six months.

Here are the factoids:

  • 725 patients with BCVI were found during the five year study period
  • Patients were propensity matched for a 1:1 ratio of patients taking antiplatelet vs anticoagulant drugs, leaving 370 patients for analysis
  • There was a lower rate of admission in the anticoagulant patients vs the antiplatelet ones (9% vs 26%)
  • There were fewer deaths within 6 months in the anticoagulated patients (1.3% vs 3.9%)
  • Median time to stroke was 6-9 days and was not significantly different between the two groups

The authors concluded that the overall stroke rate after BCVI is 6%. They also found an association with lower rates of CVA within 6 months of discharge in patients on anticoagulants. They recommend further studies to determine which type of chemoprophylaxis is best.

My comments: This is an interesting paper that addresses a problem that we don’t have good answers for. The study was well constructed and simple to follow. The two areas that I have questions about are data quality and statistical power.

The NRD is a powerful tool for research, but does have some shortcomings. It only contains information on readmissions, and may not contain some patients who had asymptomatic strokes or massively stroked and died at home. Not knowing these numbers injects some bias and could change the numbers and findings of the study.

The other issue has to do with statistical power. The overall eligible patient group (725 patients) was small in the first place. Propensity matching for a 1:1 ratio shrunk it to only 370, or 185 in each treatment group. My armchair power calculations show that this study would only be able to detect a 7x difference in mortality, and not the 3x difference seen. I’m glad the authors didn’t claim a “significant decrease in CVA” in the anticoagulated patients vs the antiplatelet drug patients.

Here are my questions for the authors:

  1. What do you see as drawbacks to data quality in your study due to use of the National Readmissions Database? How do you think that patients not included in it impacted your data?
  2. Is there anything you can do to improve the statistical power of the study to see if the mortality difference is truly different? Even though your statistical analysis shows significance, the number of subjects doesn’t allow you to claim this until the mortality in the antiplatelet group reaches 9%. 

This was a simple yet fascinating study, and is a start toward helping us determine which of the two drug classes is most appropriate for patients with BCVI.

Reference: Treatment of blunt cerebrovascular injuries: anticoagulants or antiplatelets? EAST Annual Assembly abstract #1, 2020.

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