Tag Archives: Prophylaxis

How Early Can We Start Chemoprophylaxis In TBI Patients?

We’ve learned a couple of things in the last two posts by reviewing recent systematic review / meta-analysis studies. First, low molecular weight heparin provides better prophylaxis against venous thromboembolism (VTE) than unfractionated heparin. And giving prophylaxis within the first 72 hours of admission significantly decreases the incidence of VTE with no increase in existing intracranial bleeds or mortality.

So the only remaining question is, how low can you go? That is, how soon can you safely start chemoprophylaxis? The trauma group at George Washington University in DC put together a study to examine this question.

They, and one other Level I trauma center, performed a retrospective cohort study of adult, blunt TBI patients over a three year period. Patients with penetrating brain injury, and those with any other body region with significant injury (AIS >1) were excluded so this group truly represented isolated brain injury. Other exclusion criteria were progression of blood on CT within 6 hours, and crani or death within 24 hours. Early VTE prophylaxis was defined as occurring within 24 hours, and late was > 24 hours.

All patients had hourly neuro evaluations and a repeat head CT at six hours after admission. All had compression devices applied to their legs, and received either low molecular weight (LMWH) or unfractionated heparin (UH) at a fixed dose regarding of body habitus. Anti-Factor Xa levels were not measured.

Here are the factoids:

  • Between the two centers, 264 met inclusion criteria
  • About 40% received early prophylaxis and the remaining ones received their drug after 24 hours
  • ISS was higher (18 vs 15) and GCS was lower (13 vs 14) in the late therapy group
  • About 88% of patients in the early prophylaxis group received LMWH vs only 63% in the late group
  • Average time to prophylaxis start in the early group was 17 hours vs 47 hours in the late group
  • There were no differences in bleed progression between early and late groups (5.6% vs 7%)
  • The craniotomy / craniectomy rates were the same in early and late groups (1.9% vs 2.5%)
  • VTE rate was the same in early vs late groups (0% vs 2.5%)

Bottom line: The authors concluded that there was no additional risk in giving early VTE prophylaxis in TBI patients with a stable CT seven hours after arrival. This was true for patients with subdural, epidural, subarachnoid, and intraparenchymal bleeds.

But there are some limitations to consider. This was a retrospective study, and was a “how we do it” study” as well in terms of the choice of LMWH vs UH. This means there was not protocol for the form of heparin used; that was determined by surgeon preference. 

There was also a difference in ISS and GCS between groups. However, the difference may not have been clinically significant, and it could have made the late group look worse if it were. Statistically, it did not.

And finally, the numbers are small and there was no power analysis. So there is the question of whether a significant difference could have even been detected.

What does it all mean? Well, it suggests that early (within 24 hours) chemoprophylaxis does not cause harm compared to later administration. But the study is not definitive enough to change practice yet. It should definitely prompt discussions and practice guideline development for starting prophylaxis after 24 hours of CT scan stability now. And hopefully these authors (or others) are planning a better prospective study to help us start even sooner!

Reference: Early chemoprophylaxis against venous thromboembolism in patients with traumatic brain injury. Am Surgeon 88(2):187-193, 2021.

VTE Prophylaxis And TBI

There has been a tremendous amount of gnashing of teeth regarding venous thromboembolism (VTE) prophylaxis in patients with blood in their head. This means any kind of blood: subarachnoid / epidural / subdural hematomas as well as intraparenchymal hemorrhage.

Trauma professionals have traditionally been hesitant to give any type of anticoagulant to a patient who has just bled, or who may be at risk for bleeding in the very near future. This becomes even more important in areas like the brain where management is a bit more difficult and adverse events can be devastating.

For this reason, our neurosurgical colleagues frequently like to steer the ship and dictate what type of VTE prophylaxis can be given, and when. Unfortunately, much of their advice may be driven by dogma and what they learned about the subject during their training. Having studied hundreds of TQIP reports over the past few years, I’ve learned to pick out hospitals that are relying on the advice of non-trauma surgeons to direct the prophylactic regimen.

Here are two dead giveaways that something is amiss. First, look at your TQIP report table titled “Pharmacologic VTE Prophylaxis Type.”

Compare the use of unfractionated heparin vs low molecular weight heparin (LMWH). This hospital has a huge variance from the norm compared to other comparable trauma centers. This means that “someone” is dictating its use for some subset of patients.

In my experience, this is typically a neurotrauma thing. Now take a look at the TQIP table titled “Pharmacologic VTE Prophylaxis.” Specifically, look at the “Severe TBI” cohort for time to VTE prophylaxis.

It is very clear that there is a significant delay to administering VTE prophylaxis to TBI patients. These two data points indicate that there is some reluctance to giving appropriate treatment to these patients.

The literature is clear that VTE prophylaxis is important in many trauma patients, including those with serious head injury. There are three questions that need to be answered to settle on optimal care:

  1. Which chemoprophylaxis is best, unfractionated or low molecular weight heparin?
  2. Is it better to give the selected agent earlier or later?
  3. If earlier is better, how early can we give it?

I will address each of these questions in this series of posts, focusing on neurotrauma patients. In order to try to toss out dogma, the literature I cite will be recent, no more than about two years old. So join me for battle next week as we have unfractionated vs low molecular weight heparin face off.

Thanks to Jim Sargent from Beth Israel Deaconess Medical Center for suggesting this topic.

Best Of EAST #6: How Long Does Risk For VTE Last After Spine Fracture?

Most trauma centers use an existing venous thromboembolism (VTE) guideline or have developed their own injury-specific one. These include risk factors, contraindications, specific agent, and dosing recommendations. But one thing most do not include is duration of prophylaxis!

The length of time a patient is at risk for VTE is not well delineated yet. The group at the University of Arizona decided to tackle this program using the National Readmission Database. This dataset is a comprehensive resource for critically analyzing patients who are discharged and readmitted, even for multiple occurrences. It covers 30 states and almost two thirds of the population.

The authors focused on VTE occurring during the first six months after injury. Patients who died on the initial admission, were taking anticoagulants, had spinal surgery, or sustained a spinal cord injury were excluded. Over 41,000 records from the year 2017 met these criteria.

Here are the factoids:

  • The average age was 61, which shows the skew toward the elderly with these injuries
  • Spine areas injured were cervical in 20%, thoracic in 19%, lumbar in 29%, sacrococcygeal in 11%, and multiple levels in 21%.
  • During the initial admission, 1.5% developed VTE: 0.9% were DVT and 0.7% were PE
  • Within 1 month of discharge, 0.6% of patients were readmitted for VTE: 0.4% DVT and 0.3% PE
  • In the first 6 months, 1.2% had been readmitted: 0.9% DVT and 0.6% PE
  • Mortality in the first 6 months was 6.7%
  • Factors associated with readmission for VTE included older age, discharge to a skilled nursing facility, rehab center, or care facility

The authors concluded that VTE risk remains high up to 6 months after conservatively managed spinal fractures. They recommend further study to determine the ideal prophylactic agent and duration.

Bottom line: This is a creative way of examining a difficult problem. We know that VTE risk does not stop when our patient is discharged. This is one of the few ways to get a sense of readmissions, even if it is not to the same hospital. And remember, this is an underestimate because it’s possible for a patient living near a state border to be re-hospitalized in a state not in this database.

This study might prompt us to prescribe up to six months of prophylaxis, particularly in seniors who are discharged to other care facilities.

Here are my questions for the author and presenter:

  • Is there any way to extrapolate your data to the entire population of the US, or to compensate for the “readmission over state lines” problem?
  • Is the odds ratio of 1.01 for risk of VTE in the elderly age group significant in any way? It seems like a very low number that would be easily overwhelmed by the “noise” in this data set.
  • Is the mortality number for all causes, or just VTE?

This is an intriguing study, and one that should influence the VTE guidelines in place at many trauma centers!

Reference: THE LONG-TERM RISKS OF VENOUS THROMBOEMBOLISM AFTER NON-OPERATIVELY MANAGED SPINAL FRACTURE. EAST 35th ASA, oral abstract #28.

VTE Prophylaxis After Solid Organ Injury

Venous thromboembolism (VTE)  is a common potential complication after traumatic injury. But typically, injury is associated with bleeding, so the trauma professional has to strike a balance between preventing bleeding and preventing clots.

Solid organ injury (liver and spleen, typically) is a common diagnosis after blunt trauma. Most trauma centers have protocols for VTE prophylaxis which apply to patients with those injuries. Older literature that I wrote about eight years divided the time frames for prophylaxis into early (within 3 days), late (greater than 3 days), and none. The authors of that article found that there was no association with untoward bleeding in the early group. And interestingly, there seemed to be less in that group. Unfortunately, the selection of the groups was biased, and the early VTE prophylaxis group had less severe injuries.

The surgery group at the Massachusetts General Hospital tried to clarify current practice by performing a deep dive into the Trauma Quality Improvement Program database. They searched the database to identify patients with “isolated” liver, spleen, kidney, and pancreas injury. They did this by excluding TBI, femur and pelvic fractures, spinal cord injury, and penetrating trauma. They also excluded patients with other other severe injuries with an abbreviated injury scale score of 3 or more.

The authors stratified patients into three groups: early VTE prophylaxis receiving the drug within 48 hours of arrival, intermediate within 48-72 hours, and late after 72 hours.

Here are the factoids:

  • A total of 3,223 patients met inclusion criteria
  • Prophylaxis was classified as early in 57%, intermediate in 22%, and late in 21%
  • About 3/4 received low molecular weight heparin and the remainder received unfractionated heparin
  • Late prophylaxis was associated with a 3x increase in both VTE and pulmonary embolism (PE)
  • Intermediate prophylaxis patient had a 2x increase in VTE but no increase in PE
  • Early prophylaxis showed a 2x increase in bleeding complications, especially in those with diabetes (?), spleen, and high-grade liver injury
  • A total of 60 of the 1,832 patients in the early group had bleeding events: 39 failed nonop mangement and were taken to OR, 8 underwent angioembolization, and 21 received blood transfusions

The authors concluded that early prophylaxis should be considered in patients who do not fall out as higher risk (spleen, high-grade liver, diabetics).

Bottom line: This retrospective study is probably as good as it’s going to get from a data quality standpoint. It’s larger than any single-institution series will ever be, although it suffers from the usual things most large database studies do. 

But it does show us strong associations with DVT and PE as the consequences of waiting to start VTE prophylaxis beyond 48 hours. The caveat is to be careful in certain patients, most notably diabetics and those with liver and spleen injuries, as they are at higher risk to develop complications leading to the OR or interventional radiology suite. 

I urge all of you to re-examine your VTE prophylaxis guideline and modify it to start your drug of choice as early as possible given the cautions for patients with spleen and high-grade liver injuries. The diabetes thing, well, that’s a mystery to me and I will wait for further confirmation to break those patients out separately.

If you are interested, you can see the Regions Hospital trauma program VTE guideline by clicking here.

References:

  • Thromboembolic prophylaxis with low-molecular-weight heparin in patients with blunt solid abdominal organ injuries undergoing nonoperative management: current practice and outcomes. J Trauma 70(1): 141-147, 2011.
  • Timing of thromboprophylaxis in patients with blunt abdominal solid organ injuries undergoing nonoperative management. J Trauma pulish ahead of print, October 12, 2020, doi: 10.1097/TA.0000000000002972

How To Predict Venous Thromboembolism In Pediatric Trauma

As with adults a decade ago, the incidence of venous thromboembolism (VTE) in children is now on the rise. Whereas adult VTE occurs in more than 20% of adult trauma patients without appropriate prophylaxis, it is only about 1% in kids, but increasing. There was a big push in the early 2000′s to develop screening criteria and appropriate methods to prevent VTE. But since the incidence in children was so low, there was no impetus to do the same for children.

The group at OHSU in Portland worked with a number of other US trauma centers, and created some logistic regression equations based on a large dataset from the NTDB. The authors developed and tested 5 different models, each more complex than the last. They ultimately selected a model that provided the best fit with the fewest number of variables.

The tool consists of a list of risk factors, each with an assigned point value. The total point value is then identified on a chart of the regression equation, which shows the risk of VTE in percent.

Here are the factors:

Note that the highest risk factors are age >= 13, ICU admission, and major surgery.

And here is the regression chart:

Bottom line: This is a nice tool, and it’s time for some clinical validation. So now all we have to do is figure out how much risk is too much, and determine which prophylactic tools to use at what level. The key to making this clinically usable is to have a readily available “VTE Risk Calculator” available at your fingertips to do the grunt work. Hmm, maybe I’ll chat with the authors and help develop one!

Reference: A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients. JAMA Surg 151(1):50-57, 2016.