Dear José,

You are right, plasma transfusions are dangerous treatments, and the indications must be well weighed. There are some situations were plasma is probably useful, such as in massive transfusion protocols. However, there is not much data to support plasma transfusions in other situations. Abdel-Wahab et al published an interesting paper (Transfusion 2006) in which they showed that plasma transfusions did not modify the INR in more than a hundred ICU patients with mild coagulopathy. There are other papers that do show that plasma is associated with a worse outcome (Saqib, CCM 2005; Khan, Chest 2007; Sarani, CCM 2008; Watson, J Trauma 2009). Furthermore, no one knows how to predict the risk of bleeding, as our usual coag tests (Quick, INR, aPTT) are not correlated with the risk of bleeding (Segal, Transfusion 2005). Hence, we do not even have a proper test to trigger plasma transfusions.

We are currently working on many different plasma studies, and we are looking to collaborate with other institutions who have the same concerns.

Best regards,

Oliver

Hello. I just had my disertasion on transfusion in dogs and cats. In my opinion Plasma transfusion helps, and helps a lot, especially in coagulopathies. On the other hand, The transfusion reaction that I met are none. In a retrospective study that I have started in Giessen, the reaction were seen in 2% from 224 transfusion. Anyway this article is not finished yet. In my practice I hadn't any reaction.

About specific test that can be used for tranfusion trigger and transfusion monitoring, I think that thromboelatography is a wonderfull method for those that have this. If not, PTT and aPTT may be used and even the classic slide coagulation test when you don't have anything else to monitor coagulation.

Sincerely

Meda

Dear Meda,

I would be very interested in your data about the effect of plasma. Indeed, to my knowledge, there is no convincing data to show that plasma does improve clinical outcome, except in massively bleeding patients. The data shows that plasma does partly correct very abnormal tests, but fails to correct moderately abnormal tests. And as there is no good association between coagulopathies and bleeding, nor coagulopathies and outcome, plasma has not been shown to be useful in most patients.

Thromboelastography (TEG or ROTEM) do seem promising, but the only data we currently have is in massively bleeding patients. In such a population, TEG does reduce the number of transfusions, but does not improve the outcome. And there is no data on TEG or ROTEM in non-bleeding patients, to evaluate the risk of bleeding, although it is precisely this non-bleeding population that receives the most plasma.

Sincerely,

Oliver

Dear Oliver, do we speak about human or animal patients? :)

Well, as José is an MD specialized in hemotology, I assumed we were talking about humans. But if you do have any data on improved outcome after plasma transfusions in animals, I would also be interested.

I am only human Hematologist and Hemotherapist

Several countries are using only plasma for transfusion from male donors never transfused. There is a clear relantionship between plasma from women donor - and transfused donors- and TRALI (transfusion related acute lung injury)

Methylene blue inactivated plasma has been associated with severe allergic reactions, and I fully agree that it should be avoided. Solvent Detergent (SD) treated plasma is a pooled pathogen reduced fresh frozen product with standardized volume and content of coagulation factors and coagulation inhibitors. More than 12 million 200 ml bags of the SD plasma, Octaplas (including licensees), have been produced and transfused to ca. 4 mill patients without a single documented case of TRALI and about 70% reduced frequency of allergic/immunologic reactions.

Accepted indications for the use of fresh frozen plasma are :

1. Bleeding in congenital coagulation deficiencies for which there are no specific coagulation factors.

2. Massive bleeding leeding to aquired multiple coagulation deficiency. The use of transfusion packages (i.e. 4 units of red blood cells, 4 units of plasma and 1-2 units of platelets) has been advocated.

3. Immediate rewersal of Warfarin effect in patients with active bleeding in need of volume

4. Thrombotic thrombocytic purpura (TTP)

5. DIC or consumptive coagulopaty with active bleeding

Most agree that liquid or delayed frozen plasma should not be used.

It is a pity that the above guidelines often are not followed and plasma used unnecessarily.

In Spain several prospective multicenter studies shows that TTP patients treated with Blue Metilen treated plasma (BMTP) need more sessions, more volumen, more immunosuppresor treatments, and presented higher refractory rate. Actually is forbidden at several countries, and in different spanish regions is avoid in plasma exchange.

Dear Bjarte

I could be agreed with your five indications, but

at point 3: clinical evidence shows better results with CPP

at point 1: which ones?

at point 2: war scenario results must be confirm at civil ones in RCT

Thanks

Please, don't forget that fibrinogen levels and activity in BMTP is damaged and lower.

The information you have regarding allergic reactions with MB plasma is biased. The assessment was based on 2005-2010 data in France but MB-Plasma implementation started mid-2008 in France. NO OTHER COUNTRY has reported similar results. There are papers talking about that.

The 2005-2011 data show NO DIFFERENCES between the different pathogen reduction systems used in France (quarantine, solvent-detergent, Intercept and Methylene Blue-Plasma.

MB-plasma recipients in 2011 had the LOWEST serious allergic reactions incidence when taking into account the total series between 2005-2011, independently of the type of plasma processing system used (1/206,578 units). In UK is mandatory to be used to treat children under 16 years old and the last SHOT (Serious Hazards Of Transfusion report 2011) has considered there is no reason to change.

Furthermore, Solvent-Detergent contains inportant Factor V, F-VIII and Protein S reduced levels ((RJ Benjamin, LS McLaughlin. Transfusion 2012;52:9S-19S) and vascular thrombosis risk is 3 times higher than with MB (i.e. in liver transplantation).

About TTP, I can say that the MB plasma bag contains 10% more plasma that the SD bags, so the volume transfused is higher, but the number of units maybe not. The published studies say the volume is high but the efficacy is higher than with quarantine plasma and Intercept (but this point is not commented).

Furthermore, SD has to be removed after pathogen reduction and MB has not necessary to be removed (in some countries is not).

Dear Ignacio

Spanish Apheresis group (GEA) of several spanish cientific societies (Blood Transfusion, Thrombosis and Hemostasia and Haematology and Haemotherapy: SETS, STHH and SEHH) had published several studies showing lower eficacy of MB plasma than quarantine plasma. (see attach)

In this prospective multicenter national prospective study we found that if you have to used MB treated plasma for TTP treatment (plasma exchange) we need more sessions, more volume, longer hospital stays, higher costs, and a trend to higher relapse rate.

For that, several centers in Spain ask for quarantine plasma for exchange, and also at different region MB plasma is forbidden for kids and TTP.

Dear Jose,

Thank you for the info. I had already read your article about TTP but I have some comments to point out:

There is a bias about the patients with non-initial episodes per group. Why the previous mean of previous episodes has neither been compared nor mentioned, nor included in the analysis?

'Was the homogeneity between centres assessed? Why not?

Did you looked for association between recrudescence and non-initial episodes? Maybe this would the reason for the difference.

What about adverse events? No-one happened in any group?

As is mentioned, this was not a randomized clinical trial. Then, as you know, this study does not scientifically demonstrate more than what has happened in a group of patients treated under cliical conditions. Furthermore, I don'ts see the point to decide the non-parametric statistical analysis using. The parametric are more powerful and there are transformations to correct the variance, when needed.

I can make a critical analysis about the previuous studies developed in Spain as well. There are many questions without an anwer to me to be so categorical, specially looking at the final remission and mortality rates.