Transfusasaurus(That’s you!)

Jeannie Callum, BA, MD, FRCPC, CTBS

Associate Professor, UoT

Challenges in Transfusion Medicine

• There are unique issues in every discipline that you must know– You must know the literature in more detail than

anyone else in that specialty• The worst obstetrical bleeds, the rarest indications for

IVIG, the rate of transfusion for radial vs. femoral cardiac caths, the rate of transfusion for a renal biopsy

• The information must be in your gray matter so that you have the information available for calls at 3 AM

Challenges in Transfusion Medicine

• You must be available at all times (within reason), even when not formally on call– If you assist them, they will assist you– Memorize the OR extensions, L&D, pre-admission

– call back immediately

• You must give educational sessions to general surgery, urology, orthopedics, obstetrics, oncology, BMT, neonatology, etc.– Most at 0700, annually, MDs & nursing

Teaching activities

• Subspecialty rounds• Grand rounds• Transfusion remediation• Rotations in transfusion

medicine– Cloning– Re-enforcements

• Rounds at St.Elsewhere• Bedside teaching

• Hallway teaching• Lunch & dinner teaching

at educational events• Hockey arena teaching• On-call ‘educational

sessions’• Email key studies• Ski days, golf days

Challenges in Transfusion Medicine

• You must change practice to ensure your hospital statistics stay in line with peers – the ministry is watching– You need allies in every subspecialty– You need to pick your battles with care– You need great leadership skills– You need to be a ‘YES’ person– You need some tricks on how to get people to

transfuse the right way (YOUR way)

Challenges in Transfusion Medicine

• Transfusion medicine changes rapidly– 2 Bloods– 1 Transfusion– 0.33 Transfusion Medicine Reviews– 4 NEJM– 4 Lancets– Literature search q12 weeks = 566 articles

and 16 Review articles

Case

• Order for 2 units of RBC by ENT surgeon

• Pre-transfusion hemoglobin 104 g/L

• Patient vitals are normal

• No cardiac history

• Day 1 post oral flap procedure for oral cancer

Case

• You page the ENT surgeon after a quick sprint to the ward to make sure you are not missing anything

• The ENT surgeon is new – trained at St. Elsewhere – taught to keep the hemoglobin > 120 g/L for ‘wound healing’

What do you do?

Should you fight this one?

TMR Review Process(Run by Dr. Sunny Dzik)

• 566 articles from the last 12 wks - “transfusion”, “IVIG”, “alloantibody”, “crossmatch”, etc.

• Select 20 and get the full articles• Select the best 5 of 20 (Y-N-M)• Get the list to Sunny and Richard before they nab

your articles• Analyze the article (while researching the topic)• Write a 1-2 page review• Get it done by the deadline• Await feedback from Sunny (grammar included)• Try to stay married

The benefits of reading TMR Journal Club

• You know about the articles first before your cardiologist, obstetrician, etc.– Send personalized emails to key influential

physicians with article and review attached

• Keeps your regular talks up-to-date– the information is summarized - so easy to

update talk in the week before your next session

3 articles

1 from each of us

Temporal trends in red blood cell transfusion among US dialysis

patients, 1992-2005

Ibrahim HN, et al.

Am J Kidney Disease 2008; [epub ahead of print]

Background information

• RCTs have shown that ESAs should be used to achieve a hemoglobin level of 110 g/L in CRF

• Maintenance of normal hemoglobin levels (130-150 g/L) is not associated with a better QOL and may increase the risk of cardiovascular events (2xNEJM)

• The impact of the lower hemoglobin target on RBC transfusion rates in the dialysis population has not been determined

• Actually, very little has been published on the transfusion rates in this population since the introduction of ESAs – one small study from the 1980’s shows a reduction in transfusion from Epo

Methods

• This group from the University of Minnesota performed a retrospective cohort study looking at the point prevalence of transfusion in each calendar year from 1992 to 2005 for patients insured by Medicare who were on dialysis

• A co-morbidity profile was determined for each patient based on Medicare claims in the 6-months before each year

• Patients with malignancy and hematologic diagnoses were excluded (15% of the total cohort)

Study not quite ‘up to date’

• Their time period precedes the FDA black box warning on ESAs in this population, which recommended using the lowest hemoglobin level required to avoid transfusion (May, 2007)

• So this study only tells us where we were before the drop in hemoglobin target

• So likely the transfusion rates have gone up since May, 2007

Results

• 1992 - 77,347 patients in their cohort; by 2005 – 157,000• Comparing 1992 to 2005, the patients were more likely to be:

– >75 years of age (14.4 vs. 20.8%), diabetic (30.1 vs. 54.9%), IHD (46.4 vs. 58.5%), COPD (7.7 vs. 14.6%)

• The impact of ESAs (and intravenous iron) was clearly seen on the hemoglobin levels– In 1992, 64% of patients had hemoglobin levels less than 110 g/L,

compared to 11.9% in 2004– The proportion of patients with hemoglobin levels >120 g/L

increased from 0.5% in 1992 to 38.2% in 2004– The unadjusted transfusion rates decreased from 535 units/1,000

patients to 263 units/1,000, despite more co-morbidities– This decrease in transfusion rates occurred from 1992 to 1997 and

reached a plateau thereafter

Shocking news

• Impact of time on the pre-transfusion hemoglobin level

• In 1992, the pre-transfusion hemoglobin was 92 g/L• By 2004, the pre-transfusion hemoglobin had rising

linearly to 103 g/L at a rate of 1 g/L per year• Not surprisingly, the greatest increase in blood

transfusion rate was seen in older patients with underlying atherosclerosis

• One wonders what the overall transfusion rate per 1,000 patients could have been if the transfusion trigger had remained stable at 92 g/L

Why is this study so important?

• Transfusions are being used in this patient population to reach the same hemoglobin target as recommended for ESAs, perhaps higher

• We need urgent retrospective cohort studies in this patient population in the US to look at the 2008 transfusion rates and transfusion triggers

• Backing off on ESAs at the same time as using RBC transfusions more liberally could have a major impact on the demand for blood

• We need to be looking at doing clinical trials to determine the optimal hemoglobin threshold in this rapidly growing population of patients

What do you do with this information?

• Email a copy to the head of nephrology (and dialysis if different) & your transfusion alliance in nephrology

• Add to your nephrology annual transfusion talk!

• Decide whether you need to do a review of 50-100 transfusions in your dialysis unit – Are there units to be saved?

Blood transfusion, anesthesia, surgery and risk of non-Hodgkin lymphoma in a population based

case-control study

Cerhan JR, Engels EA, Cohen W et al.

Int J Cancer 2008;123: 888-894

Background• The association between transfusion and subsequent

development of NHL is biologically plausible– TRIM, transmission of oncogenic viruses, or viral activation

• Increased use of transfusions since the 1950s may account for the increase in the incidence of NHL over the last 50 years

• Previous studies show a weak association with NHL (i.e., at worst, OR 2.0)

• The available studies are observational, and they cannot determine whether any increase in risk, observed in association with transfusion, is due to the transfusion itself or to other factors occurring in association with the transfusion

Methods• Used the Surveillance, Epidemiology and End Results (SEER)

cancer registry• Of 2,248 newly diagnosed cased of NHL from 1998-2000, the

authors were eventually able to analyze data from 759 cases• Controls were selected through random-digit dialing or from

Medicare eligibility files• Of the 2,046 controls that the authors tried to contact, 529 were

included in the study• Participants were asked numerous questions:

– Demographics– Pesticide exposure– Transfusion (<5 years, 5-29 years and 30+ years), surgery, anesthesia

history• For statistical analysis, adjustments were made for study center,

age, sex, race

Results

• The baseline variables of the 2 groups were similar in regard to age, BMI, education and race

• Several lymphoma risk factors were not reported such as infections (HIV+ excluded), autoimmune diseases and chemical/rad exposure

• A similar percentage of cases and controls (16% and 14%) had a blood transfusion.

• With adjustment, there was a non-significant trend for a higher risk of NHL for participants reporting a previous transfusion (OR: 1.26, 95%CI: 0.91-1.73), although there was no correlation with the number of transfusions

• Only transfusions given between 5-29 years before the study and given for a medical condition, 34% for anemia, were associated with a significantly increased risk

– i.e. transfusions given for trauma, OB or surgery were not associated with NHL

• There was an association between number of surgeries/anesthesia exposures and NHL

Conclusion

• The authors conclude that it is hard to imagine that transfusions for medical conditions somehow have a different effect than transfusions for surgical indications

• They believe that transfusion was simply a maker for underlying medical conditions that may lead to NHL

• Any data interpretation in this paper regarding transfusions and NHL are subject to the significant biases in this type of study (recall bias, selection bias) and the fact that asking people a question about transfusions is likely not nearly as accurate as obtaining medical records– Lots of people don’t know they have been transfused (or think they

have been)

What do you do with this information?

• You don’t need to update the hospital pamphlet for transfusion

• I would send this off to the NHL MDs at your institution– Make sure they have up to date

information when their patient ask them this question

– Don’t let the transfusion get blamed for their NHL

Transfusions in the less severely injured: does age of transfused

blood affect outcomes ?

Weinberg JA, McGwin G, Marques MB et al.

J Trauma 2008 ; 65(4) : 794-8.

Background

• This retrospective study analyzed morbidity and mortality in a group of patients all of whom received leukoreduced blood at the University of Alabama

• The study focused on those individuals with blunt trauma who were less severely injured (injury severity score < 25)– The victim of a motor vehicle accident without shock and

without penetrating trauma might be a typical case• The investigators excluded anyone who needed

blood in the first 48 hours of hospitalization or anyone who died in the first 48 hours– 90% of the units at Sunnybrook are needed in the first 24

hours…very unusual group

Methods

• Retrospective analysis spanning 7.5 years– a period during which many changes in healthcare

(unaccounted for in their analysis) might have influenced outcomes – e.g. damage control surgery, less crystalloid, scoop and run

• During those years 1,624 patients met study entry criteria, but only 430 were actually transfused

• They look at the effect of transfusion, age of blood, and other factors on mortality

Results• The authors found that those who were transfused had worse

outcomes than non-transfused patients (sicker patients get blood)

• They analyze outcomes for the volume of young storage-age blood versus volume of old storage-age blood that the patient received– morbidity and mortality was not associated with the volume of

younger (< 14 day) blood received, but that morbidity and mortality associated with the volume of older blood received (OR 1.12 (1.02 – 1.23) per unit of older storage age blood)

• They treated storage age as a dicotomous variable, categorizing blood based on day 14, as if something happens magically at day 14

• They did not control for the ABO group of the recipient (lower vWF levels in group O individuals who get fresh blood - ?less thrombosis)

Conclusion Let’s not make the same mistake again

• We convinced ourselves, largely on the basis of retrospective data, that donor leukocytes produced recipient immune suppression

• We coined a term (transfusion induced immunomodulation) to give the phenomenon even greater credence and we spent (and continue to spend) billions of dollars to “prevent it”

• However, attempts to actually prove the condition with properly controlled RCTs have largely failed

• Authors of single-center RCTs were forced to report phrases such as: – “With an increasing number of institutions converting to universal leukoreduction and the perception

of a lack of clinical equipoise, the ability to assess efficacy in a multicenter trial is no longer feasible.”

• Indeed the loss of equipoise over the role of residual donor leukocytes as an agent of imagined TRIM closed the door to the academic pursuit of the truth

• I sense we are about to make this mistake all over again• This time we seem poised to throw away equipoise on the topic of fresh versus stored

blood• We rushed towards leukoreduction last time without taking the time to actually demonstrate

whether or not we were benefiting the patient while spending society’s dollar• Will we do the same again this time ?

What should you do with this information?

• When you get asked for fresh blood for your trauma and cardiac patients…make sure the surgeons have a balanced view of this issue

• Use it to help convince your ICU to participate in RCTs of fresh vs. standard

• Advertisement: ABLE!

Questions about the other 12 articles?

Transfusasaurus(That’s you!)

Any Questions?