When I was a resident (not said in a gravely old voice…yet) Joe ran the blood bank at Walter Reed Army Medical Center teaching several years of residents throughout the national capital area everything you wanted to or needed to know about blood banking and not a lot of minutia to clog your brain in risk of losing the big picture and important need to know material. During that time Joe also taught at the Osler review course for pathology. My class and those before and after me benefited from Joe’s interests in computer programming, going through courses and quizzes written on a Macintosh! Of course, Joe at the time was the only one smart enough to have a Mac but I eventually caught on. Last but not least, around the same time Joe started the website Blood Bank Guy (no doubt with a Mac) and was responsible for our department website, still in the infancy of the Internet and later dismantled to a shell of its former shelf following increased DOD restrictions on public web content in 2001. Little remains of that today.

Fortunately, as Joe has moved on he has kept up Blood Bank Guy, lecturing, teaching and mentoring & has added podcasts and a Blood Bank Guy Blog.

Joe’s teaching style is to inform and educate through evidence-based medicine. Those of us who were fortunate to learn blood banking from Joe learned as much about the subject as we did about being effective communicators and being part of the treatment team and being able to defend your decisions that clinicians would respect. He was one of the few attendings I had who could do this and teach it.

Now if Joe could just stop being an ardent Detroit Red Wings fan, I might just have a little respect for the guy, but no one is perfect.

Look forward to your posts Joe as one of my continued references for those 3 AM blood bank calls for the right answer.

In our case, the presentation was quite classic as described in the literature and was recognized quickly by our hepatologist.  Her ceruloplasmin level (the copper carrying protein) was slightly low but was likely elevated due to an acute phase reaction.  Her urine and plasma copper were quite high (24 hour urine collection was 27180 mcg [normal 3-35 mcg]).  She underwent 4 consectutive days of plasma exchange with FFP as the replacement product and underwent an uncomplicated liver transplantation.  The following chart shows the drop in creatinine following plasmapheresis (extending the span of the red bracket) and the date of liver transplant (black arrow).

Her INR and bilirubin dropped similarly, although not quite back to normal before the transplant.  Because the clinical team suspected ongoing hemolysis and coagulopathy, she received a new liver when one became available.  As you can see in the H&E and trichrome stains of the native liver, there is clear cirrhosis.  Her hepatic parenchymal copper content (by ICP/MS) was 1103 mcg/g dry weight, which is “strongly suggestive of Wilson’s disease.”  A level of <40-50 mcg/g dry weight almost always excludes the disease.

I came into contact with this case on my Blood Bank rotation because we were asked in consultation to assess her for plasmapheresis.  Wilson’s disease is not included as an indication in the ASFA (American Society for Apheresis)’s recommendations for therapeutic apheresis, but a few case series have shown its effectiveness, especially in cases showing fulminant liver failure and hemolytic anemia.  Thus, it should probably be a category III indication (diseases with anecdotal benefit but for which there is limited data or conflicting results from published clinical trials).  The thought is that excessive copper accumulates in hepatocytes due to inherited autosomal recessive mutations in a copper transport gene, ATP7B, that codes for a P-type ATPase.  When this accumulation reaches some threshold, the liver begins to fail as hepatocytes die and release copper into the circulation, which damages erythrocytes through membrane damage or enzyme disruption.  This is thought to be the mechansim behind the hemolysis partly because of the strong, direct association of levels of serum copper and the severity of hemolysis.

Plasmapheresis effectively removes the toxic levels of copper in the circulation to disrupt the hemolytic cycle, most importantly sparing the kidneys of irreversible damage.  In some cases in the literature, plasmapheresis has been used effectively to obviate the need for liver transplantation, but in most of the cases it serves as a bridge to stabilize the patient in anticipation of a donor liver.  Many of these patients are female and have fit into an age range of 16-21, as was true in our case.

Random fact:  if you are looking for copper in your diet, you may find it in these foods: shellfish, nuts, chocolate, mushrooms, organ meats…among others.  See, you learn something new every day!

As the speaker also reminded us, aging is a process and NOT a disease.  Since I’ve been on the clinical pathology rotations of late, that made me curious: are older adults active in donating blood?  While I don’t know the specific demographic breakdown of blood donations by age, I know a fair number of older adults do donate regularly.  On the other hand, I feel there needs to be more awareness of the eligibility of older adults in blood donations.  They form a large population from which to draw and form our blood supply.

The Red Cross has no upper age limit in their eligibility criteria – you need only be “well and with no restrictions or limitations to your activities”.  Other blood centers such as mine in Milwaukee have similar guidelines – be “in good health on the day of donation”.  Because these are open for some interpretation, others may impose a 65 or 75 year age limit.  I would argue after a quick literature search that there isn’t much evidence out there to support placing age limits and that more research needs to be done.  With more and more of our population growing into the older age groups, “older” is becoming “younger” and we shouldn’t ignore this source of volunteers.

Sources:

Red Cross Website
Blood Center of Wisconsin Donor Eligibility

For my first post I’ll share an interesting case that my Blood Bank team last month was involved with, but is interesting from an Anatomic Pathology point-of-view too.  It’s identical to my post on my original blog (geniculating.blogspot.com) but I still haven’t posted the answer.  I’ve also changed some of the information to protect the patient’s privacy.

Case:

A 21-year-old female presented with a 5 week history of fatigue, anorexia, and mild jaundice. She was previously healthy with no past medical history, no medications, and no drug or medication use. The initial workup showed a normochromic, normocytic anemia (Hgb 11.5) and increased liver function tests and was negative for infectious mononucleosis and viral hepatitis. Just a few days after this basic workup her course worsened and she became more severely jaundiced and developed dark urine and right upper quadrant pain. She was admitted to a referring institution before being transferred to Milwaukee and the workup showed the following:

Afebrile and vital signs stable
Scleral icterus, jaundice, splenomegaly, and RUQ pain on exam

WBC: 13.5 H
Hgb: 6.5 L
Plt: 178
Creatinine: 2.2 H

ALT: 13
AST: 147 H
Alk phos: 17 L
Tbili: 42.9 H
Dbili: 12.6 H

INR: 3.1 H
Albumin: 2.3 L

LDH: 659 H
Haptoglobin: undetectable L
Retic: 11.79 H
Direct antiglobulin: neg.
Blood type: O+, Ab screen neg.

Peripheral smear: see image

ANA: within normal limits
Serum pregnancy test: neg.

Does anyone have a diagnosis? I’ll say that the peripheral smear is just of interest, not crucial to the diagnosis.  I thought it was just nice to see an image associated with the case.  I’ll post the diagnosis in a week with follow up photos in a new post and/or comment.