Tag Archives: Aspirin

Abstracts, Pharmacy

Best of AAST #1: Aspirin Vs Low Molecular Weight Heparin For VTE Prophylaxis

Leave a comment

The 82nd Annual Meeting of the American Association for the Surgery of Trauma begins next week. As is my custom, I will be reviewing some of the more interesting (to me) oral presentation abstracts until the last day of the meeting.

When reading abstracts, keep in mind that you are seeing just a snippet of a finished manuscript. The authors are given very little print space to fully describe their research idea, their methods, and their results’ significance. Sometimes, what is seen in the abstract varies significantly from what is actually heard at the meeting. But mercifully, this does not happen often. The abstract is usually an intriguing look at some new and exciting work.

Having said all that, an abstract should not be a reason to change your practice! It is usually early work and needs to be fully vetted at peer review. Even then, it needs to be taken in context with past, similar research before trickling down to patient care.

The first abstract is fascinating. Our orthopedic surgery colleagues have been trying to use aspirin for venous thromboembolism (VTE) prophylaxis for decades. Frequently, they are thwarted by the trauma surgeons, who are thoroughly indoctrinated in the low molecular weight heparin (LMWH) camp.

This work comes from the Shock Trauma Center in Baltimore and is a follow on to a paper published in the New England Journal of Medicine earlier this year. The paper demonstrates that aspirin is not inferior to LMWH when used for VTE prophylaxis of patients. There was no difference in death from all causes, VTE occurrence, wound complications, or bleeding events.

The abstract is a follow-on to that manuscript. The authors performed a secondary analysis of the initial data to see if aspirin provided the same apparent level of protection in patients with high risk for VTE as measured by the Caprini score.

Here are the factoids:

  • A total of 12,211 patients were enrolled in this multi-center, and the same outcomes listed above were monitored for 90 days
  • Of the total group, 3052 were judged to be high risk: 46% had a femur fracture, 42% had a pelvic/acetabular fracture, 48% had a thoracic injury, 39% had a spinal injury, and 35% had a head injury
  • There was no difference in death, deep venous thrombosis, pulmonary embolism, or bleeding in the two groups
  • Patient-reported satisfaction was significantly better by 68% in the aspirin group

The authors concluded that outcomes for aspirin vs. LMWH are similar, even in patients at high risk for VTE.

Bottom line: This is an intriguing abstract, pointing me to the original paper published in NEJM. This multi-center study was performed in conjunction with the research coordinating center at Johns Hopkins, which designs some top-notch research. This study was no exception.

I am fascinated with this work because it shows that our orthopedic colleagues were right! They’ve been trying to get us to use aspirin for a long time. It’s very cheap compared to LMWH, by a ratio of about 50,000:1. 

If you’ve followed me for a long time, you would know I have been skeptical of the VTE prophylaxis establishment. Looking historically at its evolution over the last 40+ years, the incidence of DVT and fatal PE have changed very little despite the introduction of heparin, low molecular weight heparin, and anti Factor Xa monitoring. But it’s been established practice, so we’ve had to abide by the rules. Now, a cheaper alternative to all of this is being shown to be just as (in)effective. 

I suspect that if others bear out this work, we will be able to use a cheaper prophylaxis drug that does not require injection. But we still need to work on figuring out the basis for this problem to hopefully reduce it to near zero someday.

References: 

  • Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopaedic trauma patients. AAST 2023 Plenary Paper 3.
  • Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med 2023; 388:203-213.
Pharmacy

Platelet Transfusion In Patients Taking Anti-Platelet Drugs

Leave a comment

These days, trauma professionals see quite a few patients who take antiplatelet agents for cardiovascular comorbidities. These drugs can be problematic when the patients sustain injuries that result in bleeding in problematic areas like the cranial vault.

Aspirin and clopidogrel are the most common medications, and they irreversibly inhibit platelet aggregation.  All exposed platelets essentially quit working for the remainder of their 10-day lifespan. Platelet aggregation improves slowly over time after cessation of the drug as new platelets are added to the circulation from the bone marrow.

But what can you do if you are concerned that your patient is bleeding after injury because their platelets are not working? It seems logical that you would just transfuse some new platelets. But you should know by now that not everything that makes sense really works. A group in France designed a study to test this premise in patients taking either aspirin or clopidogrel. They performed a prospective, observational study on patients presenting with potentially life-threatening hemorrhage.

The authors used the Verify Now device to measure platelet response to the two drugs. Patients who had normal platelet function in the first place (not compliant or not a responder to the therapy) were excluded. All patients had initial platelet counts greater than 100K/ml. They underwent platelet transfusion for management of hemorrhagic shock, intracranial hemorrhage, or an emergent neurosurgical procedure.

Here are the factoids:

  • Only 25 patients were enrolled during the three year study; 13 were receiving only aspirin, 8 clopidogrel only, and 4 combined therapy
  • Average transfusions were 1-2 apheresis packs of platelets (6-12 units)
  • For aspirin patients, all showed significant platelet dysfunction before transfusion, and all but one showed recovery of function post-transfusion
  • For clopidogrel patients, platelet function remained impaired; the percent of inhibited platelets decreased but remained above the study threshold for “normal” of 20%

Bottom line: This is a very small study, but drives home the point that clopidogrel and its relatives may be problematic in bleeding patients. The active metabolites of this drug class are not well understood. But they are most likely still circulating in the blood in patients actively taking them, and deactivate new platelets as soon as they are transfused (assuming that the transfused platelets have good function in the first place). 

This issue requires further study so we can really tease out the actions of the drugs and their effect on transfused platelets. Until then, carefully consider whether platelet transfusion will be helpful in your bleeding patients, and if it is even worthwhile giving them or waiting for them to finish prior to going to the operating room.

Reference: Is platelet transfusion efficient to restore platelet reactivity in patients who are responders to aspirin and/or clopidogrel before emergency surgery? J Trauma 74(5):1367-1369, 2013.

Pharmacy

DVT Prophylaxis At Home: Do Our Patients Do What They Are Told?

Leave a comment

Deep venous thrombosis (DVT) is a big potential problem for many trauma patients, particularly those with orthopedic injuries. Patients at high risk are frequently given a prophylaxis regimen to take home after discharge while they are still at higher risk for clots. The particular choice of medication typically comes down to oral (warfarin or aspirin) vs injectable (low molecular weight heparin (LMWH)).

There is quite a bit of literature on patient compliance with their medication routines, or should I say noncompliance? The group at ShockTrauma in Baltimore evaluated how well orthopedic surgery patients adhered to their prescribed DVT prophylaxis schedule after discharge.

They conducted a randomized, prospective trial on all patients who underwent operative management of extremity or pelvic fractures. These patients were prescribed either oral low dose aspirin (81mg) or subcutaneous injections of LMWH (30mg bid). All completed a standardized 8-question tool to gauge their compliance with the medication regimen. Nicely, a power analysis was performed to identify the minimum number of patients needed to achieve statistical significance ( 126 total patients).

Here are the factoids:

  • Of 1450 potential patients undergoing operative fracture fixation, 329 were eligible for the study. All but 150 were excluded primarily due to no need for prophylaxis or inability to contact.
  • Overall adherence to the prophylaxis plan was fairly high, with 65% of patients having high adherence, 21% medium, and 20% low.
  • A quarter of the LMWH patients felt “hassled” by their regimen, while only 9% of the aspirin group did
  • LMWH prophylaxis was associated with low or medium adherence
  • Having to self-administer the prophylactic agent, being a male, and young was also associated with lower compliance

Bottom line: Interesting study. And unfortunately it suggests that our patients don’t always do what they are told, especially if they have to stick themselves with needles. So they may not be getting the prophylaxis we think they are. Furthermore, we’re not even sure if aspirin (or LMWH for that matter) make a difference in the incidence of death or major pulmonary embolism in these patients.

There are a lot of opportunities for mayhem in this study. A third of the enrolled patients were not even compliant with completing the survey. This is certainly a source of bias, and most likely suggests that the overall compliance rates would have been even lower if they had. 

Keep in mind the risk factors for compliance (age, sex, drug route) when deciding how and what to provide for DVT prophylaxis. Your patient may not be doing what you assume they are!

Complications, General, Pharmacy

Aspirin For DVT Prophylaxis In Trauma

Leave a comment

The use of mechanical and pharmacologic prophylaxis for prevention of deep venous thrombosis (DVT) and venous thromboembolism (VTE) in trauma patients is nearly universal. However, no matter how closely we adhere to existing guidelines, some patients will develop these conditions. Indeed, about 80% of patient who suffer some type of VTE event were receiving prophylaxis at the time.

Trauma is a major factor in causing hypercoagulability. Although current chemoprophylaxis focuses on clotting factors, platelets play a big part in the clot formation process. Our usual drugs, though (various flavors of heparin), have no effect on them.

What about adding aspirin to the regimen? My orthopedic colleagues have been requesting this for years. There is a reasonable amount of data in their literature that it is effect in patients with knee arthroplasty only. As usual, it is misguided to try to generalize management based on experience from one specific body region or operation.

A single Level I trauma center reviewed its data on aspirin prophylaxis for trauma patients. They reviewed their registry data from 2006 to 2011. They identified 172 trauma patients with duplex ultrasound proven DVT. These patients were matched with 1,901 control patients who underwent at least one duplex and never developed DVT. Matching was performed carefully to ensure that age, probability of death, number of DVT risk factors, and presence of TBI were similar. The total number of matched patients studied was 110.

And here are the factoids:

  • About 7% of patients with DVT were on aspirin at the time of their injury, vs 14% of the matched controls
  • 7% were taking warfarin, and 4% were taking clopidogrel
  • Analysis showed that patients taking aspirin had a significantly decreased chance of DVT after injury
  • On further analysis, it was found that this effect was only significant if some form of heparin was given for prophylaxis as well.

Bottom line: So before you run off and start giving your patients aspirin, think about what this study really said. Patients taking aspirin before their injury and coupled with heparin after their injury have a lower rate of DVT. It gives us no guidance as to whether adding aspirin after the fact, or using aspirin alone, are useful.  And we still don’t know if any of this decreases pulmonary embolism or mortality rates.

Related posts:

Reference: Aspirin as added prophylaxis for deep vein thrombosis in trauma: a retrospective case-control study. J Trauma 80(4):625-30, 2016.

General

Does Aspirin Add Anything To DVT Prophylaxis?

Leave a comment

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.