Category Archives: Pharmacy

Battle of the Heparins: Unfractionated vs Low Molecular Weight

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.

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Enoxaparin And Pregnancy

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).

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How To Manage TBI In Patients On Warfarin

We all know that the combination of traumatic brain injury (TBI) and warfarin can be dangerous. Here at Regions, we developed a reversal protocol a few years ago. However, we found that just having a list of preferred “antidotes” to give was not enough. The time factor is very important, and we found that we needed to ensure prompt use of these medications when indicated.

So we added features that ensured timely response and reversal. You can download the protocol by clicking the image above or the link at the bottom of this post.

First, we recognized that any patient with a known or suspected TBI who was taking warfarin was at risk. If the initial GCS was <14, then a full trauma team activation is called. This gives the patient priority lab processing and immediate access to the CT scan. In addition, 2 units of thawed plasma are administered while in the resuscitation room. If the head CT is negative, plasma is stopped.

For patients with a GCS of 14 or 15, a “Code RED” is called, ensuring that an ED physician sees the patient immediately. A point of care INR is drawn and the patient is sent for stat head CT. If the head CT is negative with INR>2.5, the patient is admitted for observation and a repeat head CT is obtained 12 hours later. We have seen patients develop delayed hemorrhage when they have high INR.

We apply a restrictive set of criteria to determine if a patient may go home from the ED, which causes us to admit most for observation. And if they do have a positive CT, we use the algoritm listed below for comprehensive management and reversal.

Bottom line: Patients with any head trauma and an elevated INR are a walking time bomb. They need prompt assessment and reversal of their anticoagulation if indicated. Feel free to share your protocols here as well by posting a comment.

Download the full protocol; click here.

Related post:

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Another Anticoagulant To Watch Out For

In May, I wrote about a new direct thrombin inhibitor named dabigatran (Pradaxa). This drug appears beneficial for patients who need ongoing anticoagulation without the hassle of blood testing to check drug levels. The danger for trauma patients is that there is no antidote or rapid reversal possible. This means that significant traumatic bleeding, particularly in and around the brain, cannot be stopped! At Regions Hospital, we have seen a few patients on this drug, but luckily they have not had bleeding from trauma.

Late last month, Bristol-Myers Squibb and Pfizer announced that a new drug has shown very favorable results in preventing strokes in patients with atrial fibrillation (apixaban, Eliquis). Indeed, it cut the relatively low risk of stroke in half, compared to warfarin. It also had about a third fewer bleeding complications. It looks like it may also give dabigatran a run for its money.

This drug is a Factor Xa inhibitor, and also has no antidote other than time. There is some evidence that activated charcoal given orally within 3 hours of apixaban dosing may be somewhat helpful in reducing blood concentrations.

Trauma professionals need to be on the lookout for patients who use this drug. Any trauma patient who admits to being on a “blood thinner” needs to be questioned carefully to determine which one it is. If it is one of the newer drugs without an antidote, they need to be monitored continuously for signs of bleeding (read: ICU), especially if they have experienced head trauma.

Bottom line: Be on the lookout for these drugs. If any patients who have fallen are taking this drug (elderly, frequently intoxicated, etc.), contact their primary physician so that the risks vs benefits of continuing it can be considered.

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References

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Medication Alert! Dabigatran and Head Trauma

First, there was warfarin, a cheap and effective way of treating deep venous thrombosis (DVT) and pulmonary embolism (PE) in trauma patients. Unfortunately, there is plenty of literature that shows the added risk that this drug poses in injured patients, particularly in head injury. Because of this, many trauma centers have developed “rapid reversal protocols” to quickly restore vitamin K dependent clotting factors in an attempt to improve outcomes. To see our protocol, click here.

Next came clopidogrel (Plavix), which is used to prevent clotting in vascular disease. It irreversibly inhibits platelet aggregation. Counteracting this drug is more complicated due to its long half-life. Platelet infusions are required, but the infused platelets are inhibited by any remaining drug in the plasma. This requires the use of lots of platelets to get some meaningful clot to form again.

Now, we have direct thrombin inhibitors (DTI). Hirudins were the first used, and were never an issue in trauma patients. And their short half-lives obviate the need for reversal. The newest DTIs (argatroban and dabigatran) are a real problem in trauma. Argatroban is not a problem, because it is given by IV only. But dabigatran (Pradaxa) has just been approved for oral use within the last year.

According to the package insert, “there is no antidote to dabigatran etexilate or dabigatran.” And also “dabigatran can be dialyzed (protein binding is low), with the removal of about 60% of drug over 2 to 3 hours; however, data supporting this approach are limited.”

We will be seeing patients taking this drug in the near future. What do we do if they are trauma victims with bleeding in critical places, like the brain? At Regions, we have developed a proposed guideline that combines oral charcoal, dialysis, transfusions and optionally, activated Factor VII. Click here to download the protocol.

If anyone has any experience with these patients, please comment below. And everyone else, keep your fingers crossed!

Related posts:

Protocols:

Thanks to Colleen Morton MD for developing the dabigatran reversal protocol

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