Hopefully the generalization of the use of point-of- care (POC) coagulation monitoring tools will help screening the patients.

Below an interesting article discussing this point:

http://www.ncbi.nlm.nih.gov/pubmed/?term=Trauma+Bleeding+Management%3A+The+Concept+of+Goal-Directed+Primary+Care

Even if it is currently not clear which RBC:FFP ratio is the best, it is clear that bleeding patients should be treated aggressively with all the blood products available.

Thanks Clément.

I agree that POC monitoring will certainly help treat massively bleeding patients. But I'm wondering if such tests can predict the risk of bleeding in non-bleeding patients, such as those in the PICU.

Furthermore, we showed in the survey we recently published that only 27% of the institutions had a POC coagulation monitoring device. Therefore, the vast majority still relies on regular tests...

This is why we have designed this study, to see who gets plasma in the PICU, and what tests are used to guide the physician.

Dear Oliver

I have your same concern, or worst!

There are a high unjustified plasma transfusion. Probably, most of them were not well indicated. Also, most of physicians does not know what are they transfunding.

Several surveys show that is the blood component transfusion with highest variability. Also, most volume transfused is under theorycal recommend doses

Futhermore , if you analyze ratios plasma/blood cell concentrate between countries, region or hospitals, we are doing some things wrong! They are extremely variables.

Endly, we must have in mind that plasma has the highest rate of adverse reactions and transfusion death (TACO and TRALI; and there is an increasing data about the relantionship between plasma and thrombosis, and plasm group incompatiblity and worse outcomes (not only in transplant issues)

Nice idea, nice work

Good luck

I will try to promote in Spain

Thanks! We are very lucky, because there are already 72 PICUs that are going to participate, and a few more are considering it too. We'd be happy to have more Spanish centers.

The more, the merrier!

Well you should put fluids into a patient only when you have determined if you need to. Abnormal saline is tricky stuff and can lead to the patient drowning in brine. I know that you are discussing iv. plasma but it is the same deal. The British Association Parenteral and Enteral Nutrition meeting in Harrogate this week considered just this topic.and a really good primer is the excellent book by Dileep Lobo and colleagues which you can download here.

http://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CC8QFjAA&url=http%3A%2F%2Fwww.bbraun.com%2Fdocuments%2FKnowledge%2FBasic_Concepts_of_Fluid_and_Electrolyte_Therapy.pdf&ei=8ZyYUtvpIIGS7AaunYDABA&usg=AFQjCNEbZy4F6_ntdOZRNR83bkxQc0A1cQ&sig2=3mYOCRAo50N_4lhA8N7BlA&bvm=bv.57155469,d.bGE&cad=rja

The issue is definitely significant. It would be worth mentioning that only specialists should be allowed to authorize plasma transfusions depending upon the clinical condition of the patient, carefully evaluated. I am interested in the multicentre study and I will review the suggested website.

Dear George,

Thanks for the book, it's really great! Regarding the best way to resuscitate our patients, nothing is as clear as it seemed a few years ago... There is a lot of research to be done!

Claudia, it would be great of your PICU team could participate! We do not have many Italian centers...

Dear Oliver

In a recent study performed in our surgical PICU and not yet published, we found that 39%, 33% and 76% of RBC, platelet and FFP transfusions were inappropriate according to clinical guidelines.

We have tried to change the practices of the staff of our service but it is extremely difficult as the culture of our institution and unit drives them to find excuses and justification to transfusion (i.e. respiratory insufficiency, cardiac surgery, etc) in a large number of patients.

It will be a pleasure to collaborate in your study and help to find evidence to convince everyone about transfusion collateral damages.

Dear Antonio,

Thanks for sharing your data. It's a great job!

It is really amazing how much plasma is given even though it is quite often useless. Similar results have been published by Arnold et al, in an adult ICU setting. They too failed to significantly improve the transfusion strategies...

I'm looking forward to reading you study, and I hope this will be the opportunity to work together on this important question.

http://www.ncbi.nlm.nih.gov/pubmed/?term=21439762

Dear Oliver,

Thank you very much for your commitment to study the inappropriate use of plasma. I fully agree with all of you, that plasma transfusion has very few indications (e.g. severe factor V or XI deficiency and bleeding/before procedure; exchange transfusion in TTP patients; dilution coagulopathy in major bleeding) which are evidence-based; however, the number of therapeutic plasma bags ordered per year by the hospitals is much higher than the number of patients suffering from these relatively rare conditions.

For me, the question is: What are the reasons for our colleagues to give therapeutic plasma without a good indication? Is it the lack of a "good" alternative? Is it the missing information about the adverse events of therapeutic plasma? Is it the problem with hemostaseology ("plasma contains all coagulation factors; therefore, it might be the right product to correct a coagulation problem")?

I am looking forward to sseing the results of your survey!

Best wishes,

Markus

Dear All

Please read the new American Society Hematology (ASH) recommendation presented last weekend at its meeting and published at Blood (free access).

ASH Five things to reconsider: Five Things Physicians and Patients Should Question as part of Chosing Wisely.

The fourth question is: Don’t administer plasma or prothrombin complex concentrates for non-emergent reversal of vitamin K antagonists (i.e. outside of the setting

of major bleeding, intracranial hemorrhage or anticipated emergent surgery).

Once again, the evidence against the actual liberal transfusion practice!!

Please, first not harm!

Here the article!

Thanks José!

Even if this aspect is a bit off the topic, I would like to emphasize that the freely available book edited by Dileep Lobo and colleagues (which was recommended earlier in this discussion) is published by Bibliomed (located in Melsungen, Germany), a publisher who belongs to B.Braun Melsungen, a well known healthcare supplier engaged in infusion therapy. Hence, this source of information is obviously not free from industry bias. E.g., the book's section on colloids does not address the recent recommendations to avoid colloids in numerous clinical scenarios. Although I value the company's generous support for the distribution of the otherwise well-written book, I would prefer to be adequately informed about possible conflicts of interest. However, no information regarding this aspects can be found in the book.

Again: first do not harm.

Dear Hans,

Fair comment. Perhaps you should write to Dileep and ask him to update the book. He's a very approachable chap!

Hans, you are right. My modo is "Trust no one, believe nothing, give oxygen"... That is the main reason why I do this research, because we can't really trust experts' opinions when there are no solid data. In my opinion, if plasma was a new drug to be marketed, it would never be FDA approved. The only available data shows an increased morbidity and mortality, and no effect on coagulation tests. The dose has not been assessed, and there are no RCTs on the proper transfusion strategy...

Thanks again for stressing the importance of possible conflicts of interest!

By the way, we know have 85 participating PICUs!!!

Dear Oliver,

Please let me quote some recent publications:

- “… Hanging crystalloid, followed by RBCs and some plasma is passé and likely contributed to the epidemic of compartment syndromes and excess death over the last 40 years. …” Holcomb JB. A Novel and Potentially Unifying Mechanism for Shock Induced Early Coagulopathy. Editorial. Ann Surg 2011;254:201-202

- “The safest transfusion remains the one not given.” Murthi S et al. Transfusion medicine in trauma patients: an update. Expert Rev Hematol 2011; 4(5): 527–537

- restrictive transfusion strategy: “… i.e. transfuse only what is really necessary (RBCs, plasma or platelets) and only when it is really necessary.” 1A (strong recommendation, high quality evidence) (p.298) Kozek-Langenecker S et al. Management of severe perioperative bleeding. Guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30:270–382

- “Combined with the 2004 review, 80 RCTs (in 50 years, inserted by me) have investigated FP with no consistent evidence of significant benefit for prophylactic and therapeutic use across a range of indications evaluated.” Yang L et al. Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion 2012;52:1673-1686

- "Recommendation: We suggest (not: recommend, inserted by me) that plasma be transfused to trauma patients requiring massive transfusion (quality of evidence = moderate)." Roback J et al. Evidence-based practice guidelines for plasma transfusion. Transfusion 2010;50:1227-1239

These quotations can be continued for hours!

There is no doubt, that RBC will increase oxygen carrying capacity (to a certain degree).

There is no doubt, that PC will increase the number of platelets.

There is no scientific evidence, that FFP will optimize coagulation in any way! Probably with the sole exception of massive transfusion.

So, there seems to be only one solution, if you want to work "evidence-based":

Every single transfusion (i.e., RBC, PC and especially FFP) has to be indicated seperately!

FFP is only indicated in massive transfusion, but here it should be given early, in large quantities (at least 6 FFP for adults, >30 ml/kgBW and FFP:RBC >1:2 ), and fast (i.e.,~50 ml/min).

The recent discussion on side effects of HAES seems to show a class effect of all colloids in patients with compromised endothelial function. Personally, I believe, FFP will soon only be acceptable as an integrated part of an escalating management algorithm for massive transfusion.

Best wishes and a happy Christmas,

Heiko

Dear Heiko,

Thanks so much for your input! Your quotes are excellent! I agree with you, we must find a way to identify the patients who will really benefit from plasma transfusions, on an individual basis...

Kind regards,

Oliver

We are proud to announce that we have now 91 participating PICUs! This will be one of the largest epidemiological studies in transfusion medicine. Thank you all for your support!

http://www.plasmatransfusion.org