Tag Archives: platelets

Best Of AAST #7: How Do You Like Your Platelets – Warm Or Cold?

Until the last few years, massive transfusion in trauma consisted of component therapy, an admixture of packed red cells, plasma, and platelets. Whole blood transfusion is making inroads again, but it is used in a minority of centers.

Of the three components, platelets have classically required different handling than the others. They are generally kept at room temperature, while the red cells and plasma are kept very cold to preserve their shelf life. A few centers have toyed with the use of cold platelets, but there have been concerns about their ability to clot and their useful life after transfusion.

Researchers from the US Army performed a retrospective registry study on a sample of military casualties over four years. They identified soldiers who received either room-temperature or cold-stored platelets. The primary outcome was mortality, and secondary outcomes included the need for surgery, fluid and blood infusions, and the use of a massive transfusion protocol.

Here are the factoids:

  • A total of 300 patients were identified, nearly equally split between room temp platelets and cold-stored
  • Demographics of the two groups were similar, but the ISS was somewhat higher in the cold-stored platelet group
  • Significantly fewer cold-stored platelet patients underwent surgery (13% vs. 24%)
  • Survival was the same at 87-88%
  • Blood and product administration was significantly higher in the cold-stored group, as was the use of the MTP (54% vs. 34%)

The authors concluded that the use of cold-stored platelets were not inferior to room temperature platelets.

Bottom line: Huh?? Yes, survival was the same despite a higher ISS in the cold platelet group. But they required more blood and needed massive transfusion significantly more often.

I see two major issues with this study. The most important is that it is a non-inferiority study. To believe that both arms are equal, a power analysis is required. The sample size here is too small to achieve significance unless differences are extreme, like the transfusion and MTP numbers.

The second problem is that this is an association study. Attempting to show that the type of platelets used is a major determinant of survival, need for surgery, or blood product use is shortsighted. There are a myriad of other factors that have more of an impact.

Far more subjects need to be studied, and a retrospective study with limited data points is not enough. I’m surprised that a military registry could only come up with 75 patients a year to analyze. These low numbers and the nature of this particular registry could inject significant bias as well.

Stay with the room temp platelets for now, and wait for a well-powered prospective analysis before changing your MTP.

Reference: An analysis of the use of cold-stored platelets in combat trauma. AAST 2023 Plenary paper #29.

Best Of EAST #2: Pay Attention To Platelet Ratios In Your MTP!

More MTP stuff! Every trauma center has a massive transfusion protocol, and current literature encourages them to try to achieve an “optimal” transfusion ratio. The literature has converged on a red cell to plasma ratio of somewhere between 1:1 and 2:1. Less has been written about platelet ratios, and trauma centers often don’t pay as much attention to this ratio when reviewing MTPs.

But is it important? The trauma group at the Massachusetts General Hospital examined the impact of platelet ratios on mortality in patients undergoing MTP. This was another TQIP data analysis, performed over a nine year period.

The authors defined massive transfusion as ten or more units of PRBC in the first 24 hours, or any number of units of red cells, plasma, or platelets given within the first four hours. They also defined “balanced” as a ratio of RBC to FFP and RBC to platelets <2. Multivariate regression analysis was performed to gauge the impact of ratios and achievement of a balanced resuscitation on 24-hour mortality.

Here are the factoids:

  • A total of 7,520 patients in the dataset underwent MTP
  • Nearly 83% achieved RBC to FFP balance, but only 6% had RBC to platelet balance (!)
  • Patients with both balanced FFP and platelets had the lowest mortality at 24 hours
  • Mortality increased by 2x with unbalanced plasma, a little more than 2x with unbalanced platelets, and 3x if both were out of balance (see figure)

The authors concluded that the platelet component of the MTP was frequently out of balance, and that it is associated with mortality to a greater degree than with unbalanced plasma.

Bottom line: This paper confirms my observations that trauma centers pay a lot more attention to the red cell to plasma ratio and don’t get as excited when the platelets are out of line. Part of this is probably due to confusion over how to count platelet packs. Typically they are delivered in packs called “pheresis” or “apheresis.” Each is the equivalent of about 6 units of platelets (check with your blood bank for more exact numbers). This means that a ratio of 6 RBC to 5 plasma to 1 platelets would be considered balanced. But a ratio of 28:28:2 would not.

According to this abstract, the use of sufficient platelets is important. This makes sense. However, the exact mechanism cannot be determined from this type of study. It could be a direct effect of not having enough platelets to form good clot. Or it could be something completely outside the clotting mechanism, just an association with something in the care processes that occurs as these patients undergo resuscitation. 

The why doesn’t matter so much, though. This abstract presents compelling data that suggests that we really need to pay attention to the platelet ratios given during the MTP. They should be analyzed just as closely as plasma ratios during PI review, and changes to the MTP process implemented to normalize this important ratio.

Here are my questions for the authors and presenter:

  • There is a statement in the methods section that is not clear. “only patients with steady RBC/PLT and RBC/FFP ratios between 4-and 24-hr were analyzed.” What is your definition of “steady?”
  • Did you see any mortality patterns in the data you analyzed that might suggest why lower platelet volumes were more deadly?

This was a nicely done abstract, and I look forward to the live presentation and the finished manuscript!

Reference: DON’T FORGET THE PLATELETS: BALANCED TRANSFUSION AND THE INDEPENDENT IMPACT OF RBC/PLT RATIO ON MORTALITY IN MASSIVELY TRANSFUSED TRAUMA PATIENTS. EAST 25th ASA, Oral abstract #1.

Best Of EAST 2020 #2: Do Platelet Transfusions Fix Sad Platelets?

The next abstract from EAST tackles the question of how we can treat platelets that don’t work right in trauma patients. The literature on using platelet transfusions in patients who are taking anti-platelet agents is getting fairly clear: they don’t work. But what about for platelets that don’t work right due to traumatic hemorrhage?

The trauma group at Penn attacked this problem by performing a prospective study at their Level I trauma center. They investigated platelet function using thromboelastography (TEG) with platelet mapping on trauma patients admitted to the intensive care unit over a two year period. They analyzed platelet function and counts at 3, 6, 9, 12, and 24 hours after admission. Platelet function in patients given platelets during any of the intervals were compared to those who were not. Outcomes studied were improvement in platelet function and mortality.

Here are the factoids:

  • A total of 93 patients were entered into the study
  • About half (57%) had platelet dysfunction detected by TEG
  • Mortality was not different between the groups
  • Neither platelet count nor function improved with transfusion

The authors concluded that platelet dysfunction is common in these patients and that platelet transfusions do not appear to restore platelet function.

My comment: This abstract is a bit hard to follow. Hopefully the manuscript will have more detailed tables that break down which patients got platelets and at what times. It appears that patients could have gotten platelets at various times (any, all, or none) after admission to the ICU, and that pre- and post-transfusion TEG runs were analyzedfor each. It’s also not clear if every patient with dysfunction got a transfusion.

The most obvious issue here is that the total number of patients is small, and the numbers getting platelets at each time interval is even smaller (10-49). The statistical power of such a study is very low. It’s not surprising that no significant differences could be detected. This means that failing to see significance doesn’t means it’s not necessarily there, just that many more patients are needed. So it’s hard to buy into the assertion that platelet transfusions don’t matter.

Here are my questions/comments for the presenter:

  1. Why didn’t all patients get platelets? From the table, it looks like nearly all patients had significant dysfunction (defined as MAadp < 40mm) until the end of the 24 hour study period. It looks like some selection bias is possible if there was no defined protocol for giving transfusions to those who had an abnormal TEG.
  2. Is your study sufficiently powered to draw the conclusion it did? The number of patients seems small overall, and doing measurements serially every 3 hours would seem to further weaken the statistics. Please comment on your choice of analysis and how likely you are to actually be able to detect significance.
  3. Be sure to clarify the details of when platelets were given and why, how many measurements were taken and when, and exact patient numbers. These are not clear in the abstract due to length limitations.

This paper is very interesting and I look forward to its presentation.

Reference: Platelet infusions do not correct trauma induced platelet dysfunction. EAST Annual Assembly abstract #24, 2020.

Platelet Transfusion In Patients Taking Anti-Platelet Drugs

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.

EAST 2018 #3: Platelet Transfusion In Patients On Anti-Platelet Agents?

When patients with significant brain injuries present while taking drugs that interfere with clotting, we seem to have this burning desire to neutralize those drugs, right? Warfarin? Give PCC. Aspirin or clopidogrel? Well, not quite so easy. You can’t neutralize them, but can’t you just transfuse some working platelets?

That is the current practice among many clinicians, although there isn’t really much data to support it. A group at Iowa Methodist Hospital in Des Moines looked at using a commercial platelet reactivity test (PRT) to determine if platelets should be given in patients with moderate to severe TBI who were known or suspected to be taking an anti-platelet drug.

This was a retrospective study of 167 patients with a head Abbreviated Injury Scale score of 2 or higher. Patients had to have received at least 2 head CT scans in order to judge progression of any bleeds.

Here are the factoids:

  • Nearly a third of patients (29%) were non-therapeutic on their anti-platelet medication, meaning that platelet function as judged by PRT was not abnormal
  • No platelet transfusions were given to 92% of patients with non-therapeutic meds, and only 2 of these patients (4%) had clinical progression of their bleed
  • Overall, using a selective platelet transfusion policy decreased platelet transfusions and their attendant costs by about half

Bottom line: So this is one of those “how we do it” studies. This means that the authors have been doing it this way for a while, and wanted to examine the results. It is not a comparison to their historical control, but it’s likely that their current usage is much lower than it used to be. Regardless, the results are impressive, and would seem to indicate that we are throwing a lot of platelets away based on a rumor that our patient is taking an anti-platelet medication.

Here are some questions for the authors to consider before their presentation:

  • How did you define “clinically significant bleed” in the two patients that had them? Did they eventually get some platelets? Did it help?
  • Have you looked at patients that did receive platelets for an abnormal PRT to see if their platelet function improves?
  • Big picture question: What evidence is there that PRT results are meaningful? How do we know that abnormal PRT is associated with bleeding in head injured patients, or that normal PRT is not associated with it? In other words, is it a valid test?

Reference: EAST 2018 Podium abstract #4.