Tag Archives: platelets

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.

Platelet Count After Spleen Injury

In most trauma textbooks, the most commonly injured solid organ is the spleen. There is a lot of work available that tells trauma professionals how to detect and manage spleen injuries. However, the treatment of the sequelae is less clear cut. We know that the platelet count generally rises after spleen injury, and especially if it is removed. We think we know that we should be on alert if the platelet count goes over 1 M per microliter (ul) to avoid thrombisis.

What happens during the usual hospital course? Is venous thrombosis actually a problem? A group at St. Michael’s Hospital in Toronto performed a 5 year retrospective review of their patients with splenic injury to try to answer these questions. Children and patients with known pre-existing coagulopathy or that were taking anticoagulants were excluded. All were managed with prophylactic low molecular heparin, although the specific product or protocol were not described.

Here are the factoids:

  • A total of 156 patients were enrolled over 5 years. – This is a relatively low number (31/year). In contrast, here in bustling metropolitan St. Paul we see 80-100 per year.
  • Nonoperative management was performed in 84% of cases, with angio-embolization added in another 8%. The other 8% were taken to OR, where most underwent splenectomy. – This is spot on with national data. However, looking at their injury grade breakdown, it seems like they take out a higher than usual number of low grade spleens.
  • Platelet count rose steadily after admission, peaking at day 16-17.
  • Splenectomy patients had a mean peak platelet count of 890K/ul.
  • Nonop management patients had a mean peak of 604K/ul.
  • Extreme thrombocytosis (counts > 1M/ul) occurred in 25 patients (16%). It occurred in 41% of splenectomy patients, but only 6% of nonop patients.
  • Although DVT and PE occurred in these patients (8%, which seems a bit high), there was no association with thrombocytosis, extreme thrombocytosis, or aspirin use. – This is most likely due to the small size of the study. 

Bottom line: This small study provides some interesting and important information regarding the platelet count trend after splenic injury. Although there was not enough power to look at the association with DVT, PE, and the value of aspirin treatment for extreme thrombocytosis, the platelet count trend info was very interesting. It looks like we should be checking a platelet count about 2-3 weeks after injury to make sure it’s not reaching extreme levels. This can be scheduled during their postop or post-discharge visit. A reminder should also be sent to the primary care physician to be on the lookout for extreme thrombocytosis for the first three weeks post-injury.

Reference: Thrombocytosis in splenic trauma: In-hospital course and association with venous thromboembolism. Injury, in press, 2016.