The Daily Sign-Out

Reassessment of the red cell storage lesion

James C. Zimring has published a wonderful perspectives article in the April 2, 2015 issue of Blood (abstract) that nicely summarizes what is known about the red cell storage lesion from clinical and experimental studies.  However, recent RCTs (ARIPI abstract, RECESS abstract, and ABLE presentation) have failed to show in clinically significant difference between groups receiving fresher versus older blood.  So why should we bother about the red cell storage lesion when there doesn't appear to be any clinically relevant differences in outcome whether a patient is transfused with "older" blood?

 Dr. Zimring's article answers this by framing the question in terms of precisely what is known about the storage lesion, but more importantly, what is not known.  There is myriad studies describing various aspects of the storage lesion but there hasn't been that "unified theory" that really condenses all that has been described about the storage lesion into a discrete "lesion." Perhaps there isn't one.  But the author concisely outlines the limitations of clinical studies, biological studies of RBCs, and animal models of the storage lesion to build the argument that the broad question, "Is older blood bad for you?," seeks an answer that would be an oversimplification and is neither testable nor applicable.  What is needed, Dr. Zimring concludes, are more focused questions.

There are many important insights and informed in this article and I highly recommend it!

New International Society of Blood Transfusion Website

The International Society of Blood Transfusion (ISBT) recently highlighted its new website, which is more user-friendly and has links to other useful content, including their LinkedIn page and recent presentations.  You can also register for their "My ISBT" that provides additional content.

Web-based Tool for Assessing Transfusion Reactions

The Hemovigilance Module of the CDC's National Healthcare Safety Network has an open access Web application for assessing transfusion reactions that is available at www.trddx.com.  This tool is based on the NHSN Hemovigilance Module Surveillance Protocol (itself an essential resource).  This would be especially useful for general pathologists who infrequently have to assess transfusion reactions.  This is also a wonderful educational tool for pathology residents and internal medicine residents rotating through hematology-oncology services.

Other features include a table showing which diagnoses have been ruled-in, excluded or not yet tested; optional questions for assigning severity and imputability for each diagnosis; a written summary with supporting evidence of which diagnoses were established as well as those that were excluded. Finally, the user has the ability to email the written summary as a PDF document. 

I've really come to rely on this as a final check on myself and a first reference to guide pathology residents through the evaluation of a transfusion reaction.

RBC immunization in sickle cell disease--revisited

Stella Chou and co-authors published a very interesting and somewhat disquieting paper in the August 8, 2013 edition of Blood (abstract), "High prevalence of RBC immunization in sickle cell disease despite transfusion from Rh-matched minority donors."  This paper is an essential read for anyone in transfusion medicine taking care of these patients and is also of interest for its illustration of the unintended consequences of a seemingly rational policy.

The appropriate strategy to transfuse sickle cell patients to prevent alloimmunization has been controversial for several decades.  My place has maintained a policy of not providing phenotypically-matched RBCs for SCD patients.  My personal experience is probably similar to most in that most of the time, it's not a problem.  But when one these patients starts developing antibodies, especially to high-frequency antigens, it becomes a nightmamedicine.

The authors' transfusion protocol included transfusion of HbS-negative, leukoreduced, irradiated RBCs less than 21 days' old prospectively antigen-matched for D, C, E, and K antigens from ethnically-matched RBCs units through a donor program in which donors could self-identify as "African-American" and designate their donation to support children with SCD.

It is interesting, first, to compare the distribution of alloantibodies with those in the seminal study from Vichinsky et al published in NEJM in 1990.

Of 182 transfused patients, 15% of patients undergoing "episodic" transfusions and 58% of chronically transfused patients developed alloimmunization.  55% of chronically transfused and 12% of episodically transfused patients were Rh-immunized despite prophylactic Rh antigen matching.  In fact, anti-D developed in 30 patients, 29 of whom were phenotypically D-positive!  Overall, 20/50 Rh alloantibodies developed in patients POSITIVE for the corresponding antigen and 8/29 Rh antibodies were found in antigen-negative patients who received antigen-negative blood.

Perhaps the most interesting part of this study is the molecular testing that was performed to identify specific RH and RHCE genotypes in the transfused patients.  The reader is referred to the paper for more details but here's a couple of salient points:

• There was no significant difference in delayed hemolytic transfusion reaction incidence between D+ patients lacking conventional RHD and those with 1 or more conventional RHD alleles.
• The persistence of anti-D was not significantly different based on the presence of 1 or more conventional RHD alleles or the occurrence of delayed HTR and most were undetectable after 1 to 3 months.  Conversely, anti-D developing in D-negative patients persisted for long periods following detection.
• No significant difference was found in the incidence of Rh alloimmunization in 123 chronically transfused patients with only variant RH alleles, variant and conventional alleles, or only conventional alleles.
• Despite a policy of transfusing D-, C-, and E- ethnically-matched RBCs, 1 out of 6 D-negative patients made anti-D, 17 of 87 C-negative patients made anti-C, and 13 of 104 E-negative patients made anti-E.

I focused some of my time and attention on molecular immunohematology at the recent annual AABB meeting.  This paper, however, shows the limitations of molecular testing in either predicting an alloantibody response or preventing alloimmunization in this important group of transfused patients with SCD.  While diversity in the RH gene contributes to Rh alloimmunization, the pathophysiology of alloimmunization appears far more complex.

Does anemia impact hospital readmission rates after CABG surgery?

Nadine Shehata and colleagues studied this question in a recently published article (abstract) in the August 2013 issue of Transfusion.  

This is a single-institution study of 2,102 patients who underwent CABG surgery at the University of Ottawa Hospital.  224 of 2,102 patients were readmitted within 30 days after hospital discharge.  The authors collected data on a number of patient and discharge variables.

The leading causes of readmission included infection (24%), heart failure (13%), pulmonary disease (7%), and hemorrhagic disease (?)(7%).

Of the patients discharged, 48% had a discharge Hb between 8 to 10 g/dL and 42% had a discharge Hb between 10 to 12 g/dL.

Predischarge Hb was not a significant independent prognostic predictor of 30-day readmission due to all causes, readmission due to cardiac causes, or 30-day mortality.  

Factors that were associated with increased 30-day admission rates included higher co-morbidity score, leg and sternal wound infections, and post-op renal failure.

These data support the concept that anemia is an adaptive response and that even moderate anemia at the time of discharge is well-tolerated, at least as measured by 30-day hospital readmission rate.  Moreover, it supports restrictive transfusion practices in these patients.  This paper is important for hospital transfusion committees, cardiovascular surgeons, anesthesiologists, and transfusion service physicians to consider with regard to blood utilization management.

"Transfusion News" a new site launched by AABB and Ortho Clinical Diagnostics

Check out this new web site for transfusion-related news. Excellent site design and content.

AABB has partnered with Ortho Clinical Diagnostics to launch Transfusion News, a website that features videos, articles, breaking news and commentary from transfusion experts. Transfusion News will provide video updates on the 15th and 30th of each month, featuring important information about blood banking, transfusion medicine, tissue transplantation, blood policies, hematopoietic stem cells, cellular therapies and related fields. Transfusion News may be accessed through the website for the journal Transfusion, under "special features."

Source: AABB Weekly Report e-newsletter, August 3, 2012

Overview of red cell storage lesion in transfusion

The October 2011 CAP Today has a wonderful overview of the issues surrounding the clinical implications of the RBC storage lesion.  For non-blood bank geeks, this is an informative article and presents thoughtful insights and comments from a variety of perspectives.  It is much more accessible than the collection of articles from Transfusion in April, 2011 which I have had the best intentions of summarizing for this blog but just haven't been able to pull off.  These are really state-of-the-art translational research papers that I recommend if you're a specialist or want some more background after reading the CAP Today article.

There is also a helpful sidebar that summarizes the current and proposed red cell storage studies.

Lots to think about here--the translational research studies and clinical trials have the potential to really change blood banking and transfusion practices (or not).

AABB SmartBrief: Mismatched cord blood transplants can be effective

Studies: Mismatched cord blood, marrow transplants can be effective
Results of transplants with unrelated umbilical cord blood or mismatched bone marrow were comparable with results of transplants that used fully matched tissue, according to two studies involving patients with advanced leukemia or lymphoma. The studies, reported in Blood, found that the one-year survival rate for those who had unrelated cord-blood transplant was 54% and 62% for those who underwent mismatched bone marrow transplant. "Taken together, these results set the stage for a multicenter, randomized phase III trial to evaluate the relative risks and benefits" of such regimens, the researchers said. MedPage Today (7/9)

Henry VIII, the Kell blood group system and the McLeod syndrome

ScienceDaily (Mar. 3, 2011) — Blood group incompatibility between Henry VIII and his wives could have driven the Tudor king's reproductive woes, and a genetic condition related to his suspected blood group could also explain Henry's dramatic mid-life transformation into a physically and mentally-impaired tyrant who executed two of his wives.

http://www.sciencedaily.com/releases/2011/03/110303153114.htm#

Fascinating medical history article!  The Kell blood group system is probably the third most important blood group system (after ABO and Rh) because Kell antigens are highly immunogenic and Kell antibodies can cause hemolytic transfusion reactions and hemolytic disease of newborn.  Fortunately, only about 9% of whites and 2% of blacks are K positive; so although K antibodies are relatively common, it is also relatively easy to obtain K-negative blood for transfusion.

The Kell antigens are carried by a red cell membrane glycoprotein with a large globular extracellular C-terminal component.  The Kell protein interacts with the RBC surface membrane with a 37 kD protein XK (Kx antigen) which plays a key role in the expression of Kell antigens.  Interestingly, the gene encoding XK is located on the petite arm of the X chromosome and is near the foci for X-linked chronic granulomatous disease (CGD) and Duchenne muscular dystrophy (DMD).

The McLeod phenotype is a rare but clinically interesting variant in the Kell blood group system.  Individuals with this phenotype lack the Kx antigen and thus express reduced levels of Kell antigens.  This phenotype is associated with acatholytic RBC morphology and low-grade chronic hemolytic anemia.  Neuromuscular symptoms, as discussed in the article above with respect to good ol' 'enry, are frequently reported in patients with McLeod syndrome and may be related to lack of Kx expression.  Finally, the McLeod phenotype is associated with other rare syndromes, most frequently (as one might expect) with CGD and DMD or Becker muscular dystrophy.

Relationship between platelet storage and clinical outcomes

An article by Welsby and colleagues in the November issue of Transfusion examines the possible possible relationship between platelet storage duration of two to five days and the outcomes of patients undergoing coronary artery bypass graft surgery. The patients received one leukoreduced apheresis platelet product. The authors found no association between platelet storage age and clinical outcomes in this minimally transfused patient group. In addition to considering the possible clinical effects of platelet storage time, the editorial by Anne F. Eder, MD, PhD, and Gary Moroff, PhD, reviews the available evidence on the association between platelet transfusions and adverse outcomes. The authors of the editorial conclude that the question regarding the possible effect of platelet storage duration on clinical outcomes has been satisfied by Welsby and colleagues.