Tag Archives: VTE

Abstracts

Best Of EAST 2024 #8: Whole Blood And VTE

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The pendulum has swung from the use of whole blood in the early 20th century, to component therapy in the 1960s, and now a gradual move toward incorporating whole blood again. More and more papers are being published, and many trauma centers are looking for ways to integrate whole blood into their massive transfusion protocols.

Much of the literature has been dedicated to safety and effectiveness, but little has examined thrombotic complications from its use.  The trauma group at the University of Texas in Houston performed what looks to be a retrospective review of whole blood usage at two Level I trauma centers. Adult patients receiving at least one emergency-release whole blood unit were compared with those receiving only component therapy. They looked at the incidence of venous thromboembolic (VTE) complications such as pulmonary embolism (PE) or deep venous thrombosis (DVT).

Here are the factoids:

  • Nearly 3,500 patients were enrolled and were fairly evenly split between whole blood and component therapy only
  • Whole blood patients were slightly younger, were much more likely to have penetrating injury, and had significantly higher ISS (26 vs 19)
  • The whole blood patients were also significantly more likely to receive TXA, VTE chemoprophylaxis within 48 hours (86% vs. 79%) and lower 30-day survival (74% vs 84%)
  • Crude incidence of VTE was similar (7% whole blood vs. 9% component), but logistic regression “revealed that whole blood was protective of VTE,” while red cell transfusion and TXA increased VTE risk
  • Each unit of red cells increased VTE risk by 3%

The authors concluded that whole blood was associated with a 30% reduction in VTE, and TX was associated with a 2.5x increase in risk. They cautioned against the use of TXA in the setting of whole-blood resuscitation.

Bottom line: A lot is going on here. First, this is a retrospective study, which limits the number of variables that can be collected reliably. It also makes it much more difficult to perform regression analysis because there are many other possible variables to control for than just the ones collected. 

Next, as quoted in bullet point 4 above, this study can’t show that whole blood was protective, only that it was (maybe) associated with decreased VTE when the variables they collected were controlled. 

Most of the confidence intervals for the “significant” results were very close to the 1.0 line. This leaves the possibility that the result could easily be changed by adding other pertinent variables not included in the data. The only impressive one was the association of TXA exposure and VTE. I think this demands further work.

The authors need to answer several questions in their presentation to help explain the results:

  • Was there any relationship between the number of units of packed cells given and the likelihood of VTE?
  • Similarly, was there a relationship between the number of units of whole blood and possible “protection” from VTE?
  • Did you examine other physiologic or anatomic variables and their relationship with VTE? Specific ones that come to mind are shock, long bone or spine fractures, and TBI. These are some of the variables that need to be included in the regression model to improve it.

Overall, this is an interesting abstract that makes one think. But it either needs some good explanations during the presentation or additional data analysis to make it even more interesting.

Reference: Does whole blood resuscitation increase risk for venous thromboembolism in trauma patients? A comparison of component therapy vs whole blood in 3468 patients. EAST 2024, Podium paper 33.

Abstracts

Best of EAST 2024 #3: VTE Prophylaxis For Pediatric Trauma

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Venous thromboembolism (VTE) after trauma in adults has generated a considerable body of literature for guidance. However, there is much less information available regarding pediatric trauma. High-risk criteria for pediatric VTE after trauma have recently been released.

These criteria have not yet been evaluated prospectively or coupled with the administration of chemoprophylaxis. The Medical College of Wisconsin trauma group organized a prospective, multi-institutional study involving eight pediatric trauma centers. They studied VTE events within 30 days and bleeding complications. The children were stratified into three groups: no prophylaxis, early prophylaxis (within 24 hours), and late prophylaxis.

Here are the factoids:

  • A total of 460 patients were enrolled during a three-year period
  • The number of VTE events was very low at 25 (5.4%)
  • Patients who developed VTE had a median of 4 of the high-risk criteria, most commonly ICU stay>48 hours and TBI.
  • Half of patients received prophylaxis
  • VTE occurred in 1.6% receiving an early dose and 6.7% with late dosing
  • There were no bleeding complications

The authors concluded that prophylaxis in children at high risk for VTE was safe, but they could not demonstrate any risk reduction for those who had received chemoprophylaxis compared to those who had not.

Bottom line: This is another study that was cursed by low numbers. See the breakdown chart below:

There is a trend toward higher VTE in children receiving prophylaxis late or never. However, the number of subjects is far too low to detect significance. The good news is that there were no bleeding events in this modest sample of 257 patients. 

So what next? The authors state that “further subgroup analysis is ongoing to refine the high-risk criteria.” Good luck with that because subgrouping will deplete the numbers even further.

There are several things the authors could do to improve this work:

  • Get more subjects! Increase the number of centers participating, and consider sending it through the EAST Multicenter Trial process.
  • Streamline the list of high-risk criteria. There are quite a few of them. Try to focus on the most obvious ones and make sure each one has clear definitions. And set a threshold of how many must be present to trigger chemoprophylaxis.
  • Define the pediatric patient precisely. As children approach puberty, they behave more like adults as it pertains to VTE. State an explicit age cutoff.

This presentation should be a springboard to soliciting help from other pediatric trauma centers so this group can return to this meeting with compelling information.

Reference: The No Clot VTE study in high-risk pediatric trauma patients. EAST 2024 Podium paper #6.

Complications, Device

Should I Apply Compression Devices To Patients With DVT?

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Everyone knows that venous thromboembolism (VTE) is a potential problem in hospitalized patients, and especially so in trauma patients. Several groups of them are at higher risk by virtue of the particular injuries they have sustained and the activity restriction caused.

Nearly every trauma program uses some form of screening and prophylaxis in an attempt to reduce the occurrence of this problem, which can result in deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Screening looks at patient factors such as age, obesity, and previous VTE, as well as injury risk factors like spine and pelvic fractures and decreased mobility.

Based on the screening protocol, prophylaxis may be prescribed depending upon the level of VTE risk, which is then balanced with bleeding risk from the brain, solid organ, or other injuries. The choices we have are primarily mechanical vs chemical and consist of compression devices (sequential or not) and various heparins.

But an age-old question continues to resurface: if a patient breaks through their prophylaxis and develops DVT, is it safe to apply compression devices to the extremity?

There has always been the fear that doing things that increase flow in the affected extremity may cause clots to dislodge and ultimately cause a PE. Seems logical, right? But we know that often, our common sense about things is completely wrong.  Couldn’t just moving around cause pieces to break off? A meta-analysis of 13 studies published in 2015 showed that early ambulation was not associated with a higher incidence of new PE. Furthermore, patients who suffered from pain in the affected extremity noted significant improvements with early ambulation.

If ambulation makes the pain better, could the veins be recanalizing more quickly? Another study examined a small group of 72 people with DVT receiving anticoagulants, half of whom were prescribed exercise and compression stockings and the other half stockings only. There was a huge amount of variability in the rates of recanalization, but ultimately, there were no significant differences with or without exercise.

So just lying in bed is not good, and exercise/ambulation may actually make people feel better. But interestingly, bedrest alone does not appear to increase the likelihood of PE! It does decrease the risk of developing problems other than the VTE, like pulmonary complications.

But what about compression devices? Common sense would say that you are intermittently  increasing pressures in the leg veins, which could dislodge any loose clots and send them flying to the lungs, right?

Unfortunately, I couldn’t find a paper from anyone who had the courage to try this. Or perhaps no institutional review board (IRB) would approve it. But the key fact is that every compression device manufacturer includes existing DVT as a contraindication in their product documentation. They don’t have any literature either, so I assume it’s an attempt to limit litigation, just in case.

Bottom line: Walking provides at least as much muscle compression as compression devices. But the simple truth is that we have no solid research that either supports or condemns the use of active compression devices in patients with known DVT. And we probably won’t, ever.

Compression stockings seem to be safe, but they really don’t do much. They are white, but don’t do much more than contribute to hospital clothing fashion. Since the manufacturers define existing DVT as a contraindication, application of their product would be considered an off-label use. So it looks like we cannot in good faith use these devices in patients with diagnosed DVT.

References:

  • Bed Rest versus Early Ambulation with Standard Anticoagulation in The Management of Deep Vein Thrombosis: A Meta-Analysis. PLOS One , April 10, 2015, https://doi.org/10.1371/journal.pone.0121388
  • Bed Rest or Ambulation in the Initial Treatment of Patients With Acute Deep Vein Thrombosis or Pulmonary Embolism: Findings From the RIETE Registry. Chest 127(5):1631-1636, 2005.
  • Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study. J Thrombosis Thrombolysis 23:25-30, 2006.
Abstracts, Pharmacy

Best Of AAST #5: Door-To-Prophylaxis Time

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Today’s abstract continues the theme of VTE prophylaxis. The authors introduce another timing parameter in this one: the “door-to-prophylaxis” time. Just as it sounds, this is the time interval between admission to the ED and initiating chemo-prophylaxis. Just like some centers struggle with how long to wait to start it after a solid organ injury (see previous post here), many find it challenging to get it ordered in the first place.

The authors retrospectively reviewed their registry data over four years. They compared adult patients who arrived as a highest-level of activation and received blood during their resuscitation. They were divided into two groups: those with DVT or pulmonary embolism (VTE group) and those without (no VTE group). The door-to-prophylaxis time was defined as the time from hospital arrival to the first dose of medication.

Here are the factoids:

  • Just over 2,000 patients met inclusion criteria, with 106 experiencing VTE and 1,941 without it
  • VTE patients had higher ISS (29 vs. 24), higher lactate levels (4.6 vs. 3.9), and more post-ED blood transfusions (8 vs. 2)
  • There was no difference in the need for dose adjustment or missed doses between the groups
  • Door-to-prophylaxis time was significantly longer in the VTE group (35 vs. 25 hours)
  • When controlling for age, sex, ISS, lactate, and post-ED transfusions, each hour of delay increased the likelihood of VTE by 1.5%

The authors concluded that the door-to-prophylaxis time was significantly associated with increased incidence of VTE. They suggest that the door-to-prophylaxis time should be utilized as a performance improvement metric for this condition.

Bottom line: Unfortunately, we need a lot more information here. There was not enough room for details about the statistical analysis in the abstract, but they will be essential to know. And the authors remind us that this study shows association, not causation. 

Severe injury and blood transfusion are already known to be associated with a higher likelihood of VTE. The fact that the longer door-to-prophylaxis group had more frequent VTE may very well be due to their higher ISS and greater number of transfusions. Those events themselves may have led to the hesitation in starting a heparin.

Early prophylaxis is certainly a desirable goal in any trauma patient. But we need more than a new metric. We need more concrete information on the specific reasons for the delay and to prove that it is safe to give the drug early in patients who have those potential delaying factors.

Reference: “Door-to-prophylaxis” time as a novel quality improvement metric in preventing venous thromboembolism following traumatic injury. AAST 2023, Plenary paper #38.

Abdomen, Abstracts, Pharmacy

Best Of AAST #4: Starting VTE Prophylaxis After Solid Organ Injury

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Venous thromboembolic disease (VTE) continues to be a major issue in trauma patients. Most trauma centers have prophylaxis guidelines to try to reduce this problem. These guidelines typically recognize specific injuries that increase the risk of bleeding if anticoagulants are given. Typical ones include hemorrhagic injuries to the brain, pelvic and spine fractures, and solid organ injuries.

Typically, VTE prophylaxis starts immediately upon admission. But when these high-risk injuries are present, it is usually delayed for a period of time. Unfortunately, that period may be highly variable. Many centers have adopted 2-3 days to delay administration of low molecular weight heparin in patients with solid organ injury.

The AAST initiated a prospective multi-institutional trial comparing early (<48 hours after admission) and late (>48 hours) administration of prophylactic agents. Patients were older than 16 years, had any number of liver, spleen, or kidney injuries, and were initially treated nonoperatively. Patients who were transferred, died in the ED, were pregnant, had a bleeding disorder, or were taking anticoagulants or platelet inhibitors were excluded. A power analysis was performed, and more than the needed number of patients were enrolled.

Here are the factoids:

  • A total of 1173 patients were enrolled, and there were 589 liver injuries, 569 spleen injuries, and 289 kidney injuries
  • About 75% of patients (864) had early prophylaxis
  • Patients were younger (median 34 years), and two-thirds were male, with a median ISS of 22
  • Early VTE prophylaxis patients had significantly lower rates of VTE (3% vs. 7%)
  • There was no significant difference in failure of nonoperative management (5% early vs. 7% late)
  • The early prophylaxis group received fewer units of blood after prophylaxis started (17% vs. 23%)
  • Patients receiving VTE prophylaxis after 48 hours were 2.2x more likely to develop VTE

The authors concluded that early VTE chemoprophylaxis was associated with lower rates of VTE with no increase in complications. They recommended that it should become the standard of care for these patients.

Bottom line: Seeing such a well-designed and nicely executed study is refreshing. If the facts are borne out in the final manuscript review, this should become the standard of care for VTE prophylaxis in patients with solid organ injuries. 

I wish the authors would have stipulated that the chemoprophylaxis was required to be low molecular weight heparin. Unfortunately, there are still more than a few centers using unfractionated heparin. There could be a difference in efficacy and failure rates between the two. This could complicate the statistical analysis. Hopefully, the presenter will address this during the meeting.

I would also like to see a breakdown of when the early VTE prophylaxis actually started. Were they all close to 48 hours? Or were there enough at 24 hours to show this is also safe and effective?

It’s time for everyone to review their VTE prophylaxis guidelines. Get ready to make some major changes in your patients with solid organ injury!

Reference: When is it safe to start VTE prophylaxis after blunt solid organ injury? A prospective AAST multi-institutional trial. AAST 2023, Plenary paper #23.