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.
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!
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.
Reference: Aspirin as added prophylaxis for deep vein thrombosis in trauma: a retrospective case-control study. J Trauma 80(4):625-30, 2016.
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:
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.
All trauma professionals are aware of the evils of anticoagulation in patients who sustain traumatic brain injury. Warfarin is one of the most common anticoagulants encountered, but there is also a growing number of poor outcomes in patients with the newer, non-reversible agents.
But what about antiplatelet agents like aspirin and clopidogrel (Plavix)? Many physicians worry about these drugs, but is it warranted? Two Level I trauma centers in the Chicago area reviewed their experience. They retrospectively reviewed the records of patients over 40 years old who sustained blunt head trauma. A total of 1547 patients were identified over a 4 year period. They analyzed these records for in-hospital mortality, need for neurosurgical intervention, and length of stay.
Here are the factoids:
- 27% of patients were taking antiplatelet agents. Patients also taking warfarin were excluded.
- 21% were taking aspirin alone, 2% clopidogrel alone, and 4% both drugs
- Patients taking the drugs averaged about 10 years older than those who were not
- Overall, injury severity was relatively low (average ISS 10). A disproportionate number of more severely injured patients were not taking antiplatelet agents.
- There was no difference of incidence of intracranial hemorrhage (45%), neurosurgical intervention (3%), or mortality (6%) between the two groups
- Hospital length of stay averaged about 6.5 days, but long LOS was a bit more common in the antiplatelet agent group.
Bottom line: This is one more in a series of papers scrutinizing trauma and antiplatelet agents. A few previous studies have shown an adverse effect, but they have been much smaller series. I don’t believe the jury is in yet, so watch these patients carefully. A 6 or 12 hours repeat scan is probably in order, along with frequent neuro monitoring. It’s probably not worthwhile to actively try to reverse them by giving platelets unless there is obvious life-threatening hemorrhage or sudden neurologic change (see below).
Reference: Outcomes in traumatic brain injury for patients presenting on antiplatelet therapy. Am Surg 81(2):128-132, 2015.