Tag Archives: DVT

Pharmacy

Battle of the Heparins: Unfractionated vs Low Molecular Weight

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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.

Pharmacy

Enoxaparin And Pregnancy

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Pregnant women get seriously injured, too. And pregnancy is an independent risk factor for deep venous thrombosis. We reflexively start at-risk patients on prophylactic agents for DVT, the most common being enoxaparin. But is it safe to give enoxaparin during pregnancy?

Studies have looked at drug levels in cord blood when the mother is receiving enoxaparin, and none has been found. No specific bleeding complications have been identified, either. So from the baby’s standpoint, administration is probably safe.

However, there are two other issues to consider. In a study looking at the use of enoxaparin for prophylaxis in women with a mechanical heart valve, 2 of 8 women (and their babies) died. Both suffered from clots that developed and blocked the valves. Most likely, the standard dose of enoxaparin was insufficient, so monitoring of anti-Factor Xa levels must be done.

The other problem lies in the multi-dose vial of Lovenox (Sanofi-Aventis). Each 100mg vial contains 45mg of benzyl alcohol, which has been associated with a fatal “gasping syndrome” in premature infants. The individual dose syringes do not have this preservative.

Bottom line: It is probably safe to give enoxaparin to pregnant women after trauma. However, it is unclear if the dose needs to be increased to achieve adequate prophylaxis. Only consider using this medication after consultation with the patient’s obstetrician, and use only the individual dose syringes. Otherwise fall back to standard subcutaneous non-fractionated heparin (even though it is a Category C drug by FDA; it is still considered the anticoagulant of choice during pregnancy).

General

Where Do Pulmonary Emboli Really Come From?

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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.

General

Does Aspirin Add Anything To DVT Prophylaxis?

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Venous thromboembolism (VTE) is an ongoing problem for trauma professionals. Most trauma programs have settled on their own flavor of screening, prophylaxis, and treatment once the problem actually surfaces in a patient. Most prophylaxis centers around a combination of mechanical (leg squeezers) and chemical (some type of heparin) management.

Aspirin has been used for prophylaxis for elective orthopedic surgery, and occasionally in trauma patients managed by orthopedic surgeons for years. Existing literature supporting this has been sparse and unconvincing. But since VTE involves platelets as part of the process, why not have another look?

A recently published paper from Scripps in San Diego looked tried to gauge the effect of aspirin on trauma patients where taking it before they were injured. Novel idea. Can the findings be useful? The authors performed a retrospective, case-controlled study of patients who developed post-traumatic deep venous thrombosis (DVT). The patients were matched for 7 covariates, and the authors looked at an additional 26 risk factors. Those taking aspirin pre-injury were compared with those who were not.

Here are the factoids:

  • 172 cases were identified over the 5 ½ year study, and 62 (36%) were excluded because a matched control could not be found
  • 7% of the remaining110

    patients were taking aspirin (why?)

  • 13% of controls were taking aspirin
  • 7% were taking warfarin, and 4% were taking clopidogrel
  • The mean age was 52, ISS was 13-14, and hospital stay was 7-10 days (!)
  • Multivariate analysis showed a significant protective effect from DVT with a risk ratio of 0.17 (!!)
  • But this effect was found only when used in conjunction with heparin prophylaxis after admission

Bottom line: Interesting findings. What does it mean? First, this is a very small retrospective study. It was conducted over 5+ years, so changes in VTE screening and prophylaxis may have occurred at this hospital. But even so, the finding were compelling. The biggest problem is that we can’t expect people to predict that they will need to start taking aspirin. But the study does raise the interesting question of whether it might be helpful to start taking it as soon as the patient arrives at the hospital. This is one of those thought provoking studies that should prompt someone (hint hint) to design a nice prospective study to see if this ultra-cheap drug might help us bring down our VTE rates even more.

Reference: Aspirin as added prophylaxis for deep vein thrombosis in trauma: A retrospective case-control study. J Trauma 80(4):625-630, 2016.

General

A Scan That Can Find Clots Anywhere In The Body

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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.

Reference: 

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.