Transfusion in critically ill patients : short- and long-term outcomes

A blood transfusion is a common treatment for a range of conditions. Over 112 million blood transfusions are administered each year worldwide and many patients are thereby exposed to the possible risks associated with the procedure. In this thesis we focus on the critically ill patient, who is both to a great extent exposed to blood transfusion, and by his/her underlying illness, also susceptible to its adverse effects. We aimed to describe the population of the massively transfused patients and study possible negative effects associated with certain parts of the transfusion therapies. Additionally, we investigated the possibility to identify, through national health registers, the rare, but serious condition transfusion related acute lung injury (TRALI) which today is considered the leading cause of transfusion-related mortality.

In the first study we characterized the population of massively transfused patients in Sweden and Denmark during the last decades. We found a non-negligible incidence of massive transfusion with the dominating indication being major surgery. The overall mortality among massively transfused patients was high, both expressed as 30-day- and 5-year-mortality. The standardized mortality ratio (SMR) was 26.2 during the first 6 months after transfusion and decreased gradually with time but was still elevated as long as 10 years after the transfusion event.

In the second study, we studied the effect of plasma to red blood cell ratio among bleeding trauma patients. With a time-dependent model, and in contrast to previous observational data, we found no difference in outcome between high and low plasma ratio. We suggest that previous research suffered from severe bias and conclude that no strong evidence for using high plasma ratio in trauma patients exists today.

Our third study investigated a possible detrimental effect of the storage time of red blood cells. We used three different analytical approaches to assess the association between storage time of red blood cells and mortality in transfused patients. Consistently, throughout all analyses, we found no such association. Our results, which are concordant with recently published randomized controlled trials, indicate the safety of today’s practice to store red blood cells for up to 42 days.

The fourth study was performed with the aim to develop and test a statistical method for identifying donors with high risk of causing TRALI in the recipient. The statistical method was based on the diagnosis of acute respiratory distress syndrome (ARDS) among transfused patients. We constructed a risk score for each donor based on the difference between observed and expected ARDS cases among that donor´s recipients. Through this risk score we selected patients for manual review of medical records. The review resulted in identification of only one definitive TRALI case and we conclude that our statistical method, for the moment, fails to be a way of identifying and further study the condition.

List of scientific papers

I. Märit Halmin; Flaminia Chiesa; Senthil K. Vasan; Agneta Wikman; Rut Norda; Klaus Rostgaard; Ole Birger Vesterager Pedersen; Christian Erikstrup; Kaspar René Nielsen; Kjell Titlestad; Henrik Ullum; Henrik Hjalgrim; Gustaf Edgren. Epidemiology of Massive Transfusion: a Binational Study from Sweden and Denmark. Critical Care Medicine. 2016; 44:468-77.
https://doi.org/10.1097/CCM.0000000000001410

II. Märit Halmin; Fredrik Boström; Olof Brattström; Joachim Lundahl; Agneta Wikman, MD; Anders Östlund; Gustaf Edgren. Effect of Plasma-to-RBC Ratios in Trauma Patients: a Cohort Study with Time-Dependent Data. Critical Care Medicine. 2013; 41:1905-14.
https://doi.org/10.1097/CCM.0b013e31828a3214

III. Märit Halmin; Klaus Rostgaard; Brian K. Lee; Agneta Wikman; Rut Norda; Kaspar Rene Nielsen; Ole B. Pedersen; Jacob Holmqvist; Henrik Hjalgrim; Gustaf Edgren. Length of storage of red blood cells and patient survival after blood transfusion: a bi-national cohort study. Ann Int Med. 2016, 20 of December.
https://doi.org/10.7326/M16-1415

IV. Märit Halmin; Agneta Wikman; Rut Norda; Henrik Ullum; Kjell Titlestad; Ole Pedersen; Klaus Rostgaard; Henrik Hjalgrim; Gustaf Edgren. Clustering of acute respiratory distress syndrome: a statistical approach for studying transfusion-related acute lung injury. [Submitted]