Most trauma programs tend toward using low molecular weight heparin (LMWH) products for VTE prophylaxis over plain, old-fashioned unfractionated heparin (UH). How did this happen? LMWH is more expensive than UH, and there is precious little high quality research supporting it.
But, LMWH is very convenient, as it only needs to be given only once or twice daily via subq injection, whereas UH is given as a continuous infusion or subq three times a day. And a fair amount of lower quality data suggests that it is effective in decreasing deep venous thrombosis (DVT) and pulmonary embolism (PE).
This abstract comes from Sunnybrook in Toronto. The authors used sophisticated statistical models to compare centers that predominantly use LMWH to prevent VTE vs those that use UH.
Here are the factoids:
This was a huge data analysis from the ACS Trauma Quality Improvement Program database (~ 110,000 records from 214 trauma centers)
LMWH was most commonly used, 74% of the time
Patients who were more likely to need rapid reversal were more often given UH (older patients, severe TBI, early intracranial interventions)
Pulmonary embolism was significantly lower with LMWH (1.8% vs 2.4%)
This significant effect was present across all subgroups, including patients with shock, blunt multisystem injury, penetrating trunk injury, isolated orthopedic injury, and severe TBI
Trauma centers that predominantly used LMWH had significantly lower PE rates compared to UH (1.2% vs 1.8%)
Bottom line: Even given the vagaries of using huge, retrospective database reviews, this is pretty good data. The use of LMWH appears to be superior to UH in reducing the incidence of pulmonary embolism. It does not prevent it completely. But it’s a good start.
What the authors do not say, and I am curious about, is the impact on DVT. That is a much more common problem than PE. Was there any difference? Did they run out of room to comment on it in the abstract? I kind of doubt it. The devil will be in the details. Listen in on the presentation at the meeting!
Reference: Efficacy of low molecular weight heparin vs unfractionated heparin to prevent pulmonary embolism following major trauma: results from the American College of Surgeons Trauma Quality Improvement Program. AAST 2016 Paper #5.
For a long time, we “knew” that pulmonary emboli were a possible and dreaded complication of deep venous thrombosis (DVT). However, we are beginning to discover that this is not always the case. The group in San Diego decided to see if there really are two different types of PE in trauma, and what that means.
Here’s another VTE paper from Scripps Mercy Hospital, a level I trauma center in San Diego. It looked at 5 ½ years of their experience with adult trauma patients who were routinely screened for DVT. Any of these patients who developed a PE within 6 weeks of admission were evaluated further.
Here are the factoids:
Duplex screening from groin to ankle was carried out twice weekly in ICU patients, and once weekly in ward patients
Surveillance was carried out if the patient would be non-ambulatory for more than 72 hours, or were at moderate or higher risk for DVT using the ACCP guidelines
Nearly 12,000 patients were evaluated by the trauma service and 2,881 underwent surveillance
31 patients (1%) developed a PE
12 of these 31 had DVT identified before or immediately after their PE. Clot was below-knee in 9 (!), above-knee in 2, and in the IJ in one.
19 patients had PE but no DVT identified (de novo PE, DNPE)
DNPE tended to be single and peripherally located, and associated with rib fractures, pulmonary contusions, blood transfusions, and pneumonia
DVT + PE were more often found in multiple lobes or bilaterally
Bottom line: Like most, this is not a perfect study, but it’s a really good one. It is looking more and more likely that some PEs arise de novo, without any associated DVT. These clots are more likely to be linked to some type of inflammatory process, and have a tendency toward causing more of the classic signs and symptoms of PE. There are still lots of questions to be answered, like do you need to anticoagulate the de novo PEs? But for now, no change in practice. Just be aware that these might not be as bad as they seem.
Reference: Pulmonary embolism without deep venous thrombosis: de novo or missed deep venous thrombosis? J Trauma 76(5):1270-1281, 2014.
Our current technology for identifying venous thromboembolism (VTE) / deep venous thrombosis (DVT) consists of duplex ultrasonography, and sometimes, CT angiography. Both are relatively noninvasive and painless (unlike the old-fashioned venography of days gone by.
Researchers at the Massachusetts General Hospital have been working with different chemical probes that could adhere to clot and allow it to be identified on a PET scan. After experimenting with a number of fibrin-targeting peptides they settled upon one called copper fibrin-binding peptide 8 (Cu-FBP8). It was found to have a high affinity for clot, remain stable, and clear quickly from the animal.
A series of rats were subject to a surgically induced thrombus in the carotid or femoral arteries, or a sham operation. The animals were then imaged by CT/PET scan after injection with the Cu-FBP8 probe. The authors found that the probe worked as expected, identifying clot immediately. They were also able to follow resolution over the days following induction.
Here is a whole-body fused CT/PET scan of one of the animals with both carotid artery (yellow arrow) and femoral artery (blue arrows) clot.
Bottom line: This is a potentially exciting tool that could make it much easier for us to identify DVT and VTE. It could also help us understand the etiology and incidence of PE as well. But as with all animal studies, it remains to be seen whether this will translate into a useful test for humans. Stay tuned, as it will probably take about 3 years to find out the answer.
Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats. Arterioscler, Thromb, Vasc Biol 35(10):2114-2121, 2015.
We have long assumed that pulmonary emboli start as clots in the deep veins of the legs (or pelvis), then break off and float into the branches of the pulmonary artery in the lungs. A huge industry has developed around how best to deal with or prevent this problem, including mechanical devices (sequential compression devices), chemical prophylaxis (heparin products), and physical devices (IVC filters).
The really interesting thing is that less than half of patients who are diagnosed with a pulmonary embolism have identifiable clots in their leg veins. In one study, 26 of 200 patients developed DVT and 4 had a PE. However, none of the DVT patients developed an embolism, and none of the embolism patients had a DVT! How can this kind of disparity be explained?
Researchers at the Massachusetts General Hospital retrospectively looked at the correlation between DVT and PE in trauma patients over a 3 year period. DVT was screened for on a weekly basis by duplex venous ultrsonagraphy. PE was diagnoses exclusively using CT scan of the chest, but also included the pelvic and leg veins to look for a source. A total of 247 patients underwent the CT study for PE and were included in the study.
Here are the factoids:
Forty six patients had PE (39% central, 61% peripheral pulmonary arterial branches) and 18 had DVT (16 seen on the PE CT and 2 found by duplex)
Of the 46 patients with PE, only 15% had DVT
All patient groups were similar with respect to injuries, injury severity, sex, anticoagulation and lengths of stay
Interestingly, 71% of PE patients with DVT had a central PE, but only 33% of patients without DVT had a central PE.
The authors propose 4 possible explanations for their findings:
The diagnostics tools for detecting DVT are not very good.FALSE: CT evaluation is probably the “gold standard”, since venography has long since been abandoned
Many clots originate in the upper extremities. FALSE: most centers do not detect many DVTs in the arms
Leg clots do not break off to throw a PE, they dislodge cleanly and completely. FALSE: cadaver studies have not shown this to be true
Some clots may form on their own in the pulmonary artery due to endothelial inflammation or other unknown mechanisms. POSSIBLE
An invited critique scrutinizes the study’s use of diagnostics and the lack of hard evidence of clot formation in the lungs.
Bottom line: this is a very intriguing study that questions our assumptions about deep venous thrombosis and pulmonary embolism. More work will be done on this question, and I think the result will be a radical change in our use of anticoagulation and IVC filters over the next 3-5 years.
Reference: Pulmonary embolism and deep venous thrombosis in trauma: are they related? Arch Surg 144(10):928-932, 2009.
In my last post, I described a case where a fresh trauma patient was found to have an incidental finding of small, distal pulmonary embolus (PE) on her initial trauma evaluation. What should you do when you see this? Reflexively anticoagulate for months?
There are only a few papers dealing with this topic. One is from the MGH, which looked at their experience in screening for deep venous thrombosis (DVT) with duplex ultrasound and diagnosing PE with chest CT. They found that quite a few PEs were found that had no associated DVT in the legs or with clot in the pelvic veins. They also noted an interesting distribution: PEs with no DVT tended to be more distally located, and vice versa for those with DVT. This suggested that some PEs may not be emboli at all, but clot that forms spontaneously in the distal lung circulation.
Scripps Hospital in San Diego did some similar work. Only 31 of some 12,000 patients developed PE, and 19 of these had no identifiable DVT as a source. They also noted that these “de novo” PEs tended to be single and peripherally located. PE associated with DVT tended to be multiple and more central. They also noted an association with chest trauma (pulmonary contusion, rib fractures), blood transfusion, and pneumonia.
Bottom line: As usual, the literature is of little help in this relatively recently identified phenomenon. So what’s the trauma professional to do? Here’s my take. If a PE is found incidentally on the initial trauma evaluation, take a good history to see if there are any family members with clotting problems. Failing that, search for DVT using duplex ultrasound. If the PE is central or multiple, or there is a positive history or duplex screen, anticoagulate as you would any other patient with this problem. If not, carry out the usual prophylaxis and screening as laid out in your usual protocol (you have one, don’t you?), but don’t consider it a “real” PE. At least until we know more about this phenomenon.