Smilow Shares with Primary Care on Anemia

December 08, 2022

Information

December 6, 2022

Presentations by: Robert Bona, MD, Anna Kress, MD, Frank Ciminiello, MD, and Kelsey Martin, MD

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00:00I'd like to welcome you to the 4th
00:04session of Smilo shares with primary care.
00:08This is a series of talks that we think
00:12will be of interest and importance
00:15to our primary care colleagues as
00:19they are taking care of patients.
00:22And trying to best understand indications
00:25for referral and what happens when people
00:29are referred to the Smilo Cancer Center,
00:32which is such a valuable part
00:35of our health system.
00:37These talks are targeted towards
00:40primary care and the faculty panel
00:43has rotated on specific to the
00:47specialty of the talk that's being
00:51addressed and today's topic is anemia.
00:54There are many other venues for
00:56education for primary care clinicians
00:58and we know your time is valuable,
01:01so thank you so much for joining.
01:03Just for convenience,
01:04these talks will always be monthly
01:07on the 1st Tuesday from 5 to 6
01:09and there is a master schedule
01:11and we'll show you at the end the
01:14previews of the next sessions.
01:16These sessions are recorded and NE
01:19Medical Group clinicians can find
01:22those on the the clinician website
01:25under that and we will send out a link
01:28afterwards to all of those who attended.
01:31At the end of the session there will be a
01:35brief survey and please stay tuned for that.
01:41This is the schedule we will move
01:45shortly into case presentations
01:46and then the best part of these
01:49sessions is the question and answer.
01:51As you hear the presentation,
01:54please use the Q&amp;A field
01:56to queue up your questions.
01:58We will stop briefly after each of
02:01three cases to address the questions
02:03pertinent to the case and then have
02:05some open discussion at the end.
02:09I'd like to introduce our speakers
02:12on on the left, Bob Bona,
02:15who's the director of the benign hematology
02:18program and the medical director of the
02:21Hemophilia Treatment Center at Yale.
02:23He's originally from New York,
02:24and he and his wife Georgiana,
02:25are current residents of New Haven
02:28and longtime residents of Connecticut,
02:30where they raised their three children.
02:32Prior to coming to Yale,
02:34he was a founding faculty member
02:35of the Frank Netter School of
02:38Medicine at Quinnipiac University.
02:39Prior to that,
02:40he was a professor of medicine
02:42at the UConn School of Medicine,
02:43having trained there and at Saint
02:46Francis Hospital in Hartford.
02:47At the UConn School of Medicine.
02:49He did serve as the hematology and
02:51Oncology Fellowship program Director,
02:53chief of the Division of Hematology and
02:57a hemophilia treatment cancer director.
02:59He has a strong interest in his
03:02career in medical education and
03:04is a graduate of SUNY Upstate
03:06Medical College in Syracuse.
03:08I think you will see his teaching.
03:09Skills on broad display here.
03:12And Anna Crest received her medical
03:15degree from Columbia University.
03:18Vagelos College of Physicians and surgeons,
03:21her internship and residency were
03:23completed at Columbia University,
03:24New York Presbyterian Hospital.
03:27After residency,
03:28Dr Crest completed her fellowship
03:30in medical oncology and hematology
03:32at the Yale Cancer Center and served
03:33as a Chief fellow in her third year.
03:36Her clinical and research interests
03:38include various topics within
03:40classical and malignant hematology.
03:42Frank Ciminello is an internist in Trumbull,
03:45Connecticut and has over 20 years of.
03:48Experience in the medical field.
03:49He graduated from NYU School of
03:51Medicine and completed his residency
03:53in Internal Medicine primary care
03:55at the University of Pennsylvania.
03:58He also has an MBA from the Yale School
04:00of Management and currently serves
04:02as both a Regional Medical director
04:04for Northeast Medical Group in the
04:07Bridgeport Region and also as the
04:09President of the Primed Medical Group,
04:11which is a PSA group within NE Medical Group.
04:15Kelsey Martin,
04:16our final panelist,
04:18is an assistant professor of
04:20clinical medicine at the Yale
04:22Cancer Center and Cares for patients
04:24at the SMILO Cancer Center.
04:27In Orange,
04:27CT,
04:28she received her medical degree from
04:30the Royal College of Surgeons in
04:32Dublin and completed her residency
04:34in internal medicine at the Jacobi
04:36Medical Albert Einstein College
04:38of Medicine in New York.
04:39She subsequently completed specialty
04:41training in hematology and medical
04:44oncology at Lenox Hill Hospital
04:46in New York City.
04:47Doctor Martin's clinical interests
04:49are patient communication,
04:50hematology,
04:50hematologic disorders in women's
04:53cancer prevention,
04:54including the role of nutrition.
04:56Obesity and an environment in cancer
04:59promotion.
05:00Doctor Martin is actively involved
05:01in the Yale community as a member
05:04of the Status of Women in Medicine
05:06and the Women Faculty Forum.
05:08With that said,
05:09I think you have a lot of learning
05:11in front of you and I'm going to turn
05:14to over to our panelist to begin.
05:16Frank,
05:17do you want to introduce the first case?
05:20Thank you and.
05:24Well you just put yourself on mute
05:26I muted unmuted and muted again
05:28myself so sorry about that.
05:31So we have three cases I'll I'll
05:33present them and then each of the
05:36our our panelists are specialists
05:38will will help guide us through
05:40some discussions some work up and
05:43and and we hope this is extremely
05:45educational and beneficial to you
05:47and and your patience and as I'm sure
05:51you know anemia is extremely common.
05:53And and it seems as patients get
05:56older the the chances are the
05:58prevalence of anemia really does
06:00increase quite dramatically.
06:01So we we hope these three cases
06:04which we picked from literally a
06:07week of my patients a few weeks ago
06:09is is relevant for you as well.
06:14So case one is a is a woman 52 year
06:16old woman who is coming in for a
06:19routine physical she's a history of
06:21thyroid disease, sleep apnea, diabetes.
06:23And you can see her current blood
06:27work which showed an anemia and
06:30and the prior year showed a little
06:33less severe anemia,
06:35but you'll notice a drop in
06:38hemoglobin and a drop in her MCV
06:41although MCV is still normal.
06:44And then, uh,
06:45next slide and there's a routine village.
06:47You had no symptoms at all.
06:50Um, get next slide, please.
06:54I am trying to move to the next
06:57slide and it's not working.
07:01I've been having some network problems.
07:03Renee, can you pull up this slide deck?
07:06I'm going to stop. Sharing.
07:09Actually I can try resharing one
07:11more time and see if that works.
07:15No, it's not working right now.
07:18Have you? Pull it up.
07:24Apologies for the delay.
07:30Um, oh, there we go.
07:33Alright, so we sent her for some additional
07:37blood work and you'll see her iron
07:39levels tsat TABC, which is now high.
07:42Her ferritin is low and her B12 was normal.
07:46She did have a colonoscopy the
07:48prior year that showed us a benign
07:52hyperplastic polyp and diverticulosis.
07:55And uh, if we can go to the next slide,
07:57actually those questions,
07:59yeah, sorry the the.
08:01So I'll hand it off to Kelsey,
08:04but beforehand,
08:05we'll ask Kelsey, you know,
08:07what other tests she would want done
08:09by us or that we should do first and
08:12any recommendations for treatment
08:14and then when we would want to
08:16refer this person to hematology.
08:18Alright, thank you.
08:20Alright. Thank you so much for
08:22the opportunity this evening.
08:23Frank, would you mind just flipping back
08:25to the labs that we did already perfect.
08:27So I think in looking at this case,
08:30I think what jumps off the page
08:32to me right away is that you know
08:34that hemoglobin hematocrit dropped
08:36in about a year's time span as you
08:38mentioned the MCV started to decrease.
08:40The platelet count was also kind of
08:43heading towards the upper limit of
08:46normal and the MCV and I'm sorry the RDW
08:49is also starting to increase as well.
08:51I think these labs as far really
08:54clearly consistent with iron deficiency.
08:56The ferritin being less than 30 really
08:59is as a number we would look at.
09:01So certainly if it's less than 10,
09:03I think that this is clear cut
09:05iron deficiency,
09:05a retic count I think is helpful
09:07just to sort of to to show sort
09:09of the lack of narrow response.
09:11The peripheral smear is always I think
09:13useful to in hematology and and I
09:16think actually truthfully I think if
09:18if the patient is is not describing
09:21significant bleeding or history of bleeding.
09:23I may even be content with stopping there.
09:27I think if a patient is giving a history
09:29of a long standing history of bleeding,
09:32particularly something like a menstrual,
09:34bleeding will come into that in a second.
09:36And as a hematologist,
09:37I do start to think about bleeding
09:40disorders as well,
09:41things like von Willebrands disease that
09:43are that are common in the population and
09:45that can manifest as iron deficiency.
09:47And so I actually would probably
09:49not do too much more at this point.
09:51I actually think we have enough
09:52of a diagnosis to make.
09:58So and.
10:02We can break.
10:04Iron deficiency is extremely common.
10:06A significant burden globally
10:09and disproportionately
10:10impacts children and women.
10:13We can break down the main etiologies
10:16or causes of iron deficiency.
10:18Most commonly here we're seeing
10:20things like chronic blood loss,
10:21GI blood loss.
10:22Particularly in a man until proven
10:25otherwise and postmenopausal
10:27women's menstrual bleeding,
10:29gynecological bleeding and and Gu bleeding,
10:33sort of the second sort of
10:35major category be malabsorption.
10:37And this we see commonly I
10:40think in our patients with a
10:42history of bariatric surgery as
10:44obesity and continues to rise.
10:46And also Umm H pylori is another
10:48quite common thing I feel that
10:50we see in the outpatient setting.
10:54And then there is sort of another second,
10:57third major category would
10:59be sort of physiologic need.
11:00So you know, periods of growth,
11:02childhood, adolescence and certainly
11:05during pregnancy where nearly half of
11:09pregnant women are iron deficient.
11:13So we could flip the next slide.
11:17So we think specifically looking at
11:20more pathologic disorders associated
11:22with iron deficiency and as mentioned
11:24in this patient's case, she had seen.
11:29Gastroenterology not in the
11:30recent future right played Frank.
11:32It was in the last year or two in this case.
11:36But always important for us to
11:38think about the entire job GI tract.
11:41I think particularly about H
11:44pylori again as an as an NPI,
11:47that's something that we see that
11:49can contribute to or hydria,
11:51which can also contribute to iron deficiency.
11:56We sometimes are screening patients
11:57for celiac disease as well,
11:59I think UM and that it comes up
12:01often in our patients who are
12:03also refractured iron which I'll
12:05come back to in a couple slides.
12:07And then there is a number of
12:09conditions as well that we see
12:11frequently and particularly in
12:12the primary care setting of anemia
12:14associated with chronic disease where
12:16those patients or maybe have poor
12:18utilization of of iron and and that's
12:21patients with chronic heart failure,
12:24chronic kidney disease and other.
12:26Chronic inflammatory disorders,
12:27particularly things like
12:29inflammatory bowel disease,
12:31I listed on the right hand side
12:33here just a couple of other
12:35things I feel that we see often
12:37in our practice as hematologists.
12:39So I think food insecurity and sort
12:42maybe for access to diverse diet,
12:45diet is something that we should
12:48probably dig into a little bit deeper
12:50with our patients as we take a history.
12:52Blood donation and I have a a
12:54number of patients who are those
12:56frequent blood donors you know who
12:58are donating their blood every you
13:00know between 50 to 60 days and and
13:03there's and they're saying to just
13:05support those types of patients
13:07should be on oral iron supplementation
13:09to prevent iron deficiency.
13:12So I think again a good history
13:14comes comes in handy there as
13:17mentioned before gynecologic bleeding
13:18you know iron deficiency again
13:21disproportionately impacts.
13:22And then?
13:23And have you menstrual periods is
13:25is common and so working closely
13:28with our gynecologists can be
13:30tremendously helpful in improving
13:32the quality of life of of of women
13:35with iron deficiency and and asking
13:37about hematuria and just other
13:39sources of of blood loss.
13:41And then patients who receive
13:44erythropoietin stimulating agents
13:46or darbepoetin for example,
13:49those patients use up their iron stores
13:51over time and it's important that they are.
13:53Also receiving.
13:56Iron supplementation so important
13:58as we look in patients medications
14:01to to see if that's playing a role.
14:03And we also know by researchers
14:06from here at Yale that Trimberg
14:08for example that there are genetic
14:12conditions where some people do not
14:15absorb iron adequately and that's
14:17due to inappropriately increased
14:18levels of hepcidin which is our
14:21master regulator of of iron.
14:23So we think about that a lot in
14:25patients who have been taking.
14:27Iron supplements appropriately,
14:28but are not not achieving an adequate
14:32response. Next slide, please.
14:36And a couple of just clinical pearls
14:39perhaps are things to consider?
14:42An iron deficiency can can be due
14:44to more than one thing at a time.
14:47And in dual pathology for example,
14:50both upper and GI tract involvement
14:51is found in about 1 to 10% of
14:53cases and and and with our aging
14:56population this becomes more common.
15:01In both males and postmenopausal women,
15:03cancer of the GI tract is
15:05found about 8 to 10% of cases,
15:07which is quite significant.
15:08In our pre menopausal women, women.
15:12Cancer of the GI tract is is much less
15:15common and and heavy menstrual periods
15:17would be playing a major role in that case.
15:21Next slide, so for the ferritin
15:23is probably the most single most
15:25useful test we can have performed.
15:28And going back to your question
15:30about what additional testing can be
15:32done and and if it's low which is is
15:34really characterized by less than 15
15:36to 30 and then then you've already
15:39confirmed absolute iron deficiency
15:40and and that's why with that prior
15:43case I think with a ferritin of
15:45three that was very helpful to have
15:47an iron saturation of less than
15:4920% is is also another useful.
15:51A target and when doctor bonus speaks,
15:53I think he's going to you know
15:56make reference to how we how we
15:59interpret situations where patients
16:00may still be iron deficient yet
16:03have anemia of chronic disease.
16:04So, so important to pay attention
16:06to that iron saturation,
16:07the peripheral smear can show us
16:09classic findings of iron deficiency
16:11and the reticulocyte count,
16:13RDW and platelet count are also
16:16all factor into my decision making
16:18process as I evaluate these patients.
16:22Umm.
16:23I think in history,
16:24I I will come back to that in
16:26that I don't think much additional
16:27lab work is required,
16:28but I think a strong history taking
16:30our strong history taking skills are
16:32really useful and asking patients if
16:34they're craving ice or being crunchy things.
16:37I think it's also very helpful and also
16:42quite specific for iron deficiency.
16:46And so I asked that often of my patients
16:48and other things like restless leg syndrome,
16:51cold intolerance which I feel like
16:53patients mention often and and I do,
16:55I do find that patients mention
16:57alopecia as a as a concern should I'll
17:00bring our attention to iron deficiency
17:03and maybe out of the scope of today,
17:05but certainly patients maybe carries
17:07a beta thalassemia and it can be
17:10sometimes challenging when someone
17:12has a microcytic anemia to help
17:14make that distinction.
17:16And the Mentor Index is a is a tool
17:19worth the MCV over the RBC Count,
17:21which can help us, you know,
17:24try to make that distinction.
17:26And excited.
17:29Something I've thought about and
17:31I thought maybe others might do
17:33is you know should our patients be
17:34fasting when we when we check iron
17:36levels and I think it can be,
17:39but it doesn't have to be.
17:40It's how I interpret the data.
17:42I'm not sure if my colleague should
17:45answer this but I I think that
17:46there are some diurnal variations
17:49and also some changes after meals
17:51that that impact serum iron and and
17:54and so our serum iron levels peak
17:57in the late morning and it also.
17:59Increases after a meal.
18:02But it also decreases after fasting
18:04and so my interpretation of this
18:07is that I think it
18:08is not is not crucial to to to
18:12measure iron studies fasting but.
18:15Sort of on the on the flip side,
18:16on the other end of the spectrum
18:18where sometimes we see very high
18:20levels of of iron and we're sending
18:22patients to that for hemochromatosis
18:23and those patients I will often
18:26have them repeat it fasting in that
18:29circumstance and it it appears that
18:31the tsap performs just as well in non
18:35fasting versus fasting patients so.
18:37Next slide, please.
18:40So our goals of treatment or
18:42management of iron deficiency,
18:43we want to first and foremost identify
18:45and treat the underlying cause of the
18:48end deficiency and working typically
18:51closely with our gynecologist and
18:53gastroenterologist colleagues is key.
18:56And maybe less commonly, urology,
18:58we want to replete the iron stores and
19:00we want to normalize the hemoglobin if
19:02someone's anemic and improve or reverse
19:04the symptoms that they're experiencing.
19:06And usually, you know,
19:08the craving of ice ships,
19:10you know, response quite quickly.
19:11And I often remind patients to bring
19:13that to our attention if they notice
19:16it in the future because it's such a
19:19sensitive sign and the goal is not
19:20to keep patients on lifelong iron.
19:22And as I'm sure, as we've all seen,
19:24Umm, sometimes it's a medication
19:25that seems to linger on medication.
19:27Lists.
19:27And I think it's always worth
19:29reevaluating whether the patient
19:30really truly still needs to be on it.
19:32So. Next slide, please.
19:37So what is the best approach?
19:40So in our.
19:41Case that patient team was around 9:00
19:43and I think this patient has Frank
19:45you said was largely asymptomatic
19:47and probably this patient could be
19:49managed with oral iron supplements.
19:52Patients often I find ask you know
19:55can they just eat eat more meat or or
19:58make a change and I think that's is
20:01limited and it's in its efficacy once
20:03patients are becoming progressively
20:05anemic but but could be considered if
20:08if someone has a normal hemoglobin
20:11but maybe borderline iron levels.
20:13I think it's that reasonable to to
20:15try and I've just listed some some
20:18some foods that are rich in iron
20:20and Anaheim iron from from from meat
20:22or poultry and fish is is absorbed
20:24more efficiently than iron that
20:25comes from plant based sources.
20:27But I would you know certainly
20:29doesn't have to be what someone
20:32needs if they're vegan for example.
20:35I think if there's one thing that
20:37people in the audience want to listen
20:39to today is how to to give oral iron.
20:43And we now have a growing collection
20:46of data that that tells us that every
20:49other day iron supplementation is,
20:51is the way to go.
20:52And we're really no longer giving
20:55iron daily and certainly not daily
20:58in in 3 divided doses as as, as,
21:01as Epic automatically orders it.
21:04So, Umm,
21:05and and it's it's easy to remember
21:07about 100 milligrams of elemental
21:09iron every other day.
21:11I think 1 can't go wrong and and this
21:15is the the the reason behind this is.
21:18Sort of.
21:19If,
21:19if there's a really simplistic way
21:21is if there's kind of too much
21:24consistent iron that hepcidin,
21:25which again is sort of our master
21:27regulator of iron absorption,
21:29starts to impair our ability to
21:31absorb further iron,
21:32and taking the iron every other day is best.
21:36It's also best on an empty stomach,
21:39hour before 2 hours after a meal.
21:43You know,
21:44regarding the rule of vitamin C
21:48from from from my understanding,
21:49there's really no data to sort
21:51of fully make this
21:52recommendation.
21:52I often personally don't.
21:53I'm not sure if my colleagues
21:55would answer that,
21:55but I never really push for it.
21:57But it doesn't bother me
21:59if someone's taking it.
22:01And it really needs to be
22:03continued for a few months.
22:05At least three to six months
22:07after the iron deficiency has
22:08been corrected in order to
22:10to replenish those stores.
22:11So it takes a few months for it
22:14to be effective and and I would
22:15just keep that in mind as again
22:17as we make decisions about which
22:19patients might might need to have.
22:21Their anemia improved quicker and
22:23as we talked about intravenous iron.
22:27Also, a lot of patients can't tolerate it.
22:28You know more.
22:29You know,
22:29somewhere between 30 to 70% of patients have,
22:32you know, usually GI upset.
22:36As a result,
22:38there's a number of different
22:40brands on the available.
22:41Usually do recommend fair
22:43sulfate because I think it has
22:45the most data supporting it,
22:47and I I personally am weary of
22:51slow release formulations because
22:54its absorption is passed the
22:56duodenum where iron is absorbed.
22:58So I'm personally wary that I'd be
23:00curious with my colleagues say about that.
23:02Umm.
23:04Next slide,
23:05please.
23:08We as hematologists offer
23:10a lot of intravenous iron.
23:13And the patients who I consider
23:16it in are largely those patients
23:18who are either intolerant or
23:20sort of failed oral iron therapy.
23:23Many of our patients also have
23:26malabsorption medical conditions,
23:28patients with gastric bypass for example,
23:29or patients with inflammatory bowel
23:32disease where the utilization of iron
23:35given intravenously is much more efficient.
23:39As I mentioned,
23:39it takes a few months for oral
23:41iron to be effective,
23:42so sometimes we need to improve
23:44things quickly.
23:45Maybe someone is going to
23:47have surgery or if someone is.
23:5134 weeks pregnant and and we need to
23:54improve their anemia in a shorter time
23:56frame and I think intravenous iron is
23:59extremely helpful in those situations.
24:01It is also common in patients who
24:04are with chronic kidney disease on
24:07erythropoietin stimulating agents often
24:11benefit from intravenous iron. Umm.
24:21We have ways of calculating the iron deficit.
24:25That calculation is stated there.
24:28It usually ends up being somewhere around
24:301000 milligrams that someone needs repleted,
24:33and there's a number of different
24:36brands that are available.
24:38They. At the end of the day,
24:42can I think we choose which brand
24:45based on patients, insurance and and?
24:51Potentially, how many visits
24:52it might be to the clinic.
24:54Some of them require more
24:57more than one visit. Umm.
25:00There is evolving literature
25:02about the risk of infusion related
25:05reactions that can happen with iron.
25:10Including our own published
25:11data that seems to be maybe
25:13relevant to patients blood type,
25:14but I think it still is quite rare,
25:17maybe maybe somewhere around 1%
25:19of patients have what we call an
25:21infusion related or which is a
25:24sort of allergic type reaction.
25:25But for the most part there's no brand
25:29preference at the end of the day.
25:34Next slide, please.
25:37So who should be sent to hematology,
25:40I think patients who who who benefit
25:42from IV iron will always happy to
25:45see those patients and I think if
25:47the patient is having a history
25:49with significant bleeding and that
25:52includes a heavy menstrual periods.
25:54Patients who have prolonged menstrual
25:56periods, patients who see clots
25:57of blood during their periods,
25:58patients who say every woman in
26:00their family had heavy periods,
26:01I think it can be very helpful for
26:03us to make sure those patients
26:05do not have a bleeding disorder.
26:07Patients who bleed after pregnancy,
26:09these are patients who are frequently
26:12missed in their diagnosis and then
26:14patients who are refractory to patients
26:17who have been taking oral iron appropriately.
26:19So again, I just think back on,
26:21are they taking it every other day,
26:23are they taking it,
26:24are they taking on empty stomach,
26:25are they,
26:25are they are they taking it the way we've
26:28recommended for patients that really are or?
26:32I think it can be helpful for
26:33us to to think outside the box a
26:34little bit as to what the cause of
26:36their iron deficiency is.
26:41Good. I'll just pop in one of
26:43the questions on Katie Reeve,
26:45who's one of our EMG internist in the New
26:49London region or the Far East region,
26:52says other than pill burden,
26:54is there a downside to long-term
26:56iron that people aren't feeling
26:58side effects are their harms?
27:01Well because the there's no,
27:04there's no real way for our the human
27:07body to get rid of excess iron.
27:09I do worry about iron overload
27:12and occasionally I think we do.
27:14We do see patients who start to have
27:18high duration and high ferritin from
27:20being on you know a long standing iron.
27:23So I I do think, I do think.
27:26It really should just be done
27:28for a fine out amount of time.
27:30Alright. And Doctor Zarko Power just
27:33points out that you know chronic blood
27:36loss especially angiodysplasia and other
27:39GI issues on seems to be really common.
27:41And I'll add one more question.
27:43Sometimes we use the platelet
27:46count as a kind of approximator
27:48of how acute the bleeding is.
27:51Is there any truth to that that people
27:52who have a high platelet count with
27:54their iron deficiency are more likely
27:56actively bleeding than than than not?
28:02I'm not aware of that.
28:04I don't know the answer to that.
28:05I I feel like we see.
28:09And I actually think so when I did some
28:11of the research that that that the the
28:13platelet count is is often high in iron
28:16deficiency through its own mechanism.
28:17So I but I I don't know how bleeding
28:20offsets that's why I actually just
28:21don't know the answer to that question.
28:24I don't know I'll defer to my colleague
28:26someone else has a nose of more than
28:28I do but I and I but I absolutely
28:30agree with interact with ours about
28:32Andrew dysplasia and and and we do have
28:34some patients I think that are kind
28:35of chronic leaders and and for those
28:37patients I think yes they could stay on iron.
28:39As long as you're someone's
28:40like tracking it and measuring.
28:43OK. But.
28:48So I'll, I'll take this back.
28:50Thank you, Kelsey, very much.
28:52And even though I prepared these cases
28:54and knew what you're going to say,
28:56I still learned three things just now.
28:59So thank you. So this woman did have
29:04manraja on more directed questioning
29:07and ultrasound that showed polyps.
29:09She had a GYN who took her surgery.
29:12She did well after surgery.
29:15And she's had a normal hemoglobin
29:17postop and and since and still
29:20without any symptoms which is great.
29:23So and I think she had just
29:26oral iron I believe in the end.
29:30Thank you. I think we answered.
29:34Yes, I think we answered all
29:35of our questions for case one.
29:37So I'm going to move us through to case two.
29:41So SN is another patient of mine,
29:4376 year old gentleman a little older,
29:45a little bit thicker coronary artery disease,
29:47prefer all disease Tia, stroke, COPD,
29:53chronic kidney disease stage 3.
29:58Which is not in there but that's what
30:01he has who came in with the subacute
30:05of one to two-month history of chronic
30:08dyspnea on exertion that over that
30:11time period has been getting worse.
30:14Here's his most recent blood work
30:17and I was calculating his GFR by
30:20memory but I might have overshot.
30:22But you can see he is anemic
30:25hemoglobin of nine his ferritin.
30:28Was in the normal range of B12 in the upper
30:32normal range and his platelets were normal,
30:36his MCV normal.
30:40We'll go and through the next slide
30:44for a little bit more history.
30:47We did a a fit card that was negative
30:50because of his comorbidities.
30:51Um, he was probably just about due for
30:54a colonoscopy now and the decision
30:57really wasn't to do unless we had to.
30:59But his colonoscopy exactly 10 years
31:02ago was essentially normal as well,
31:05diverticulosis and and internal hemorrhoids.
31:07So I'm going to pass it on to
31:10Bob Bona and the questions first
31:13would be what other testing would
31:16you recommend in this case? Thank
31:18you. Thanks, Frank.
31:19And just to echo Kelsey,
31:22I appreciate the opportunity to be here
31:24this evening to speaking with all of you,
31:26it's a it's a real pleasure.
31:28And so just to recap,
31:30this is a a man in his 70s who has
31:33multiple medical issues who now has
31:36some symptoms of dyspnea and has what
31:39I would characterize in many of us
31:42would characterize as a moderate anemia.
31:44And I think what other
31:46tests would you recommend?
31:48I think it's always helpful to know what
31:51the previous CBC values are certainly
31:54is this anemia developed rather quickly,
31:57has it been present for
31:58many years or many months,
32:00in which case the the dyspnea
32:01may not be related to the anemia.
32:03So having those values is really
32:06very helpful and also keeping in
32:09mind that individuals who develop
32:11anemia slowly have a great capacity.
32:14To to to compensate for that and may
32:17and may or may not have symptoms
32:20until they get quite anemic.
32:22The Reticulocyte count is really
32:24a must in this situation,
32:26I think where we're looking at in
32:28anemia where it's not so straightforward.
32:30And then a peripheral blood smear I
32:33think is always a very reasonable
32:35thing to request from our pathology
32:37colleagues to get any clues about what
32:40this anemia could be could be due to.
32:44The the maybe there I'm going to come to
32:46as we go through this case if I could.
32:48So if if you could please
32:51just advance the slide.
32:53So I just want to spend a minute
32:55talking about reticulocytes if I
32:57can because I think there's a lot
32:59of confusion about how these are
33:01reported and how these are interpreted.
33:03So most of us know that these are
33:06have been reported as percents,
33:09reticular site percent and then
33:10where we've been taught to calculate
33:12a reticular site production index
33:14or a curriculum.
33:15Corrected reticulocyte count.
33:17And then look at that number and to determine
33:21if the anemia is hypo proliferative.
33:23That is from the point of
33:25view of the blood smear,
33:26bone marrow not producing blood
33:29cells or hyperproliferative.
33:31Again, if you're standing out in the blood,
33:33the bone marrow producing a lot of blood,
33:36a lot of blood cells,
33:37the bone marrow are producing
33:38a lot of blood cells,
33:40and I personally find that
33:41many of us do that.
33:43The absolute reticulocyte count is
33:45probably the best way to think about this.
33:48And just a moment,
33:49just a a word about that.
33:51So if the normal red count is 5
33:54* 10 to the six per microliter
33:56of 5,000,000 per microliter.
33:58And the red blood cell survival
34:01is 100 days or so.
34:03We therefore replace about 1% of
34:06our red blood cells every day.
34:08So our reticulocyte count is 1% * 5
34:12* 10 to the 6th, 1% of 5,000,000,
34:16and that's 50,000.
34:18And sometimes this is reported as 50,000.
34:22Sometimes in the Yale lab it's reported
34:24as a number of times 10 to the 6th.
34:27So it comes out to point.
34:2905 and I and I think again understanding
34:32how that's reported is important.
34:34And so if a person has an anemia and has a
34:38reticulocyte count of 50 or 60 or 70,000,
34:40they are under producing red blood cells
34:43and the bone and the bone marrow is
34:46not able to compensate for the anemia.
34:48And on the other hand, if the articular
34:51side can is 150,000 for instance,
34:53that suggests that the bone
34:55marrow is producing a lot of red
34:57blood cells despite the anemia.
34:59And this is critically important
35:01because there are only a couple of
35:03things that give an anemia with
35:05an elevated reticulocyte count.
35:06And one of those is of course hemolysis.
35:09With an adequate bone marrow response,
35:12you can have homolysis and not have
35:14an elevated reticular site count.
35:15So if you have iron deficiency for instance.
35:18Plus hemolysis,
35:19the bone marrow can't respond.
35:22The other thing that will give an
35:24increased reticulocyte count is that
35:26there's some recovery from an anemic process.
35:28So someone's had a bleed and
35:29you're seeing them a week or two
35:31later and they're recovering.
35:33Or as in the previous case
35:35that Kelsey discussed you,
35:36you're giving someone iron and
35:38their anemia is getting better.
35:39And in those cases, again,
35:41you'd expect the reticulocyte count to be
35:44increased as the bone marrow is recovering.
35:47And just as a quick reminder,
35:48those.
35:49Particular sites are the bigger,
35:50bluer cells on the peripheral
35:52blood smear indicated by the arrow.
35:55So for me,
35:56absolute reticulocyte count is a
35:58very important number that I look at
36:01to try to help decipher the anemia.
36:05And then if, yeah, if we could move.
36:07Thank you.
36:09So the blood smear is also very
36:12important and especially if there are
36:16some characteristic abnormalities described.
36:18So for instance, if there are teardrop
36:21cells noted on the peripheral blood smear,
36:24we're often thinking of myelofibrosis
36:27or myelopoiesis.
36:28Myelopoiesis, of course,
36:29is where there's something invading
36:31the bone marrow.
36:32That could be cancer.
36:33It could be infection like tuberculosis.
36:36It could be granulomas with sarcoid
36:38for instance.
36:39So the presence of teardrops is helpful.
36:42Burr cells are often seen in uremia
36:44spur cells and liver disease target
36:47cells and liver disease, etcetera.
36:49So I won't go through the list,
36:51but these things you know can really
36:53help us a lot and give us clues as to
36:56why the patient is developing anemia.
36:59And we would either look at the
37:01smear in clinic ourselves or ask
37:03our pathology colleagues to look
37:05at this and then give a formal.
37:07Report in the chart.
37:11Thank you. And so back to this case,
37:16I think represents one of the harder
37:19cases of anemia for me as a practicing
37:22hematologist because you have a
37:24patient who has multiple medical
37:26problems who has a moderate anemia,
37:29one that we can't just say
37:30is just a tiny bit off.
37:32You know, there's something going on
37:34here with the hemoglobin of 9 grams.
37:37And and it's normal chromic
37:39and presumably it's, sorry,
37:41it's Norma acidic and
37:43presumably normochromic.
37:44And I'm going to assume here that the
37:46reticulocyte count is low in this case.
37:48So these are hard,
37:50hard anemias to decipher because there
37:53are many things that can cause the
37:56anemia and there are and and likely
37:59multifactorial causes of the anemia.
38:01And at the end of the day
38:02when I see someone like this,
38:04the question that's in my mind
38:05is do they need.
38:07Bone marrow biopsy,
38:07do we need to suggest a bone
38:10marrow aspiration biopsy,
38:11determine the cause of the anemia?
38:14And on the left there is just kind of a
38:17broad overview of the classifications
38:19for anemia, bone marrow failure,
38:21bone marrow replacement,
38:22nutritional or hormone deficiency,
38:25etcetera.
38:26And then on the right is kind of
38:28the thinking that I will go through
38:30when I see a patient like this.
38:32So is this anemia urgent and we do,
38:35we needs to do something today.
38:37Tomorrow. So is it new and severe?
38:41Is the patient significantly symptomatic
38:42where they might need an intervention,
38:45for instance,
38:46like a blood transfusion from the anemia?
38:48We don't usually expect that
38:50with the hemoglobin of nine,
38:51but if someone had a hemoglobin of
38:5314 yesterday and they're nine today,
38:55they are going to be symptomatic and
38:58will likely need some urgent intervention.
39:01And so the history is quite important
39:03here to help us understand that in
39:06terms of the development of this anemia.
39:08And then the other thing to think
39:10about is there some other process
39:11that's life threatening going on here
39:13that we need to deal with right away?
39:14Is this TTP, for instance,
39:16so are there just a sites on the blood smear?
39:18Is there thrombocytopenia as well?
39:21Are there myeloblasts on the blood smear?
39:23So this may be an acute leukemia.
39:25So those are kind of things that we
39:28often need to think about right away.
39:30Because those patients really need to be
39:33seen right away and triaged differently.
39:35If those things are not present,
39:38so I'm thinking about it,
39:40could this be bone marrow invasion
39:42with cancer for instance?
39:44And so a good history,
39:46a good physical exam are really,
39:47really important here.
39:48Has there been weight loss,
39:50other sweats, fevers, is there a mass,
39:53is there a history of cancer?
39:56Is there frequent urination with with
39:58prostate enlargement and a possibility
40:00of prostate cancer for instance,
40:03because prostate cancer and bone marrow.
40:05Invasion is not uncommon.
40:08I always will think about
40:10multiple myeloma in this setting.
40:12So a normochromic anemia in
40:14an older individual I think
40:16who also has some chronic kidney disease.
40:19We we need to make sure we're not
40:22missing multiple myeloma and it often
40:24I will get protein studies in these
40:26individuals and those will include
40:28a serum protein electrophoresis and
40:31immunofixation electrophoresis and serum
40:33free light chains because about 20%
40:36of individuals with multiple myeloma.
40:39Will not have an M spike on their serum
40:43protein electrophoresis and the serum
40:46free light chains will be abnormal.
40:49I'm often thinking about in
40:52chronic inflammation here.
40:53There are a number of disorders this
40:55patient has that cause chronic inflammation.
40:58So I might be thinking about a
41:00SED rate or CRP,
41:01or I might think that's
41:03superfluous at this point,
41:04that the patient does have chronic
41:06inflammation and I don't really
41:08need to get a SED rate.
41:09But one of the things that I'm also
41:11thinking about is temporal arteritis.
41:13And in my history I'm asking about headaches,
41:16I'm asking about weakness in the shoulders,
41:19and I'm pressing on the temporal.
41:20Arteries when I examine a patient
41:23like this cause another diagnosis
41:24that you certainly don't want to
41:26miss and is is a common diagnosis.
41:29And even though this anemia is
41:31not microcytic or macrocytic with
41:33the way we usually think about
41:35nutritional deficiencies,
41:36I am going also going to think about a
41:39nutritional deficiency here as combined
41:41with anemia of chronic inflammation or
41:43as a possible multifactorial process.
41:46So even though this is not normal,
41:48not microcytic or macrocytic.
41:50I certainly will worry about this.
41:52Anemia of chronic inflammation is also
41:55something we would think about and if
41:58you could go to the next slide please.
42:00So this person does have stage 3
42:02chronic kidney disease and about
42:0417% of patients with chronic kidney
42:07disease stage three will have anemia.
42:09And the next slide please,
42:11a very important slide here because I
42:14think this slide demonstrates to us
42:17that if you have a ferritin that is.
42:21200 or less with an iron saturation
42:23of 20% or less,
42:25you can still have iron deficiency if
42:27you have chronic kidney disease and
42:29the ferritin might even be as high as
42:32500 if you have more advanced kidney disease.
42:35And then so the final slide.
42:39Is that what I would do?
42:40I would certainly do the things we
42:43talked about the previous red cell CBC
42:46values or ticad peripheral blood count.
42:49I would probably give this person oral
42:51iron and see what happens with their
42:54anemia before I went off on a on a a
42:58workup that included a bone marrow biopsy.
43:00I think if this person didn't get
43:02better with oral iron or had monoclonal
43:04proteins in their blood or there was
43:06some other reason to suspect cancer,
43:08I would refer this patient.
43:10To hematology.
43:11So I would hope that this patient
43:14gets better with with iron,
43:16but otherwise I think I would refer this
43:19patient for an evaluation by a hematologist.
43:24Great, thank. Thank you very, very much.
43:26I had one questions on the retic count,
43:29I would do more and then we'll move to
43:32the next case just so we can stay on time.
43:35You know one of those hallmarks of teaching
43:38and residency that I I still remember is.
43:40Uh if you have someone with who
43:42might have iron deficiency anemia
43:44and you give them iron and the,
43:46you know the first thing that might
43:49improve before their hemoglobin is the
43:51retic count to know that if they're
43:53responding and just would just sort of
43:55ask if that's still common teaching
43:57and and something that we can follow
43:59because we'll see someone in two weeks.
44:01Let's say we put them on iron and
44:03if we hadn't had the retic before
44:04but check it now it,
44:06would it still be helpful to know
44:08that maybe we're on the right track?
44:10Yeah, absolutely, frank.
44:11The reticulocyte count should
44:12be the first thing to respond.
44:14And and now we get some
44:17additional fancier tests that
44:19you may see sometimes there,
44:20articulus reticulocyte,
44:21hemoglobin content.
44:22So that's just what it is,
44:25the amount of hemoglobin in
44:26particular sites and that often
44:28will respond even before the
44:29reticular site count does.
44:31OK. All right. Thank you. Ohh.
44:36All right. And and we do have one,
44:37it totally falls into this question here.
44:40How quickly do we expect to see a rise
44:42in the hemoglobin with iron supplement?
44:47I'll tell you what I remember is,
44:49um, if they're appropriately dosed,
44:53it's usually 1 gram and three to four weeks.
44:57But I got 3 experts here,
44:59so correct me if I'm wrong.
45:03That's how I remember it. Frank,
45:04is about a gram of hemoglobin in
45:06the first month improvement. Yeah.
45:09All right, great. Thank you.
45:11All right. Uh case 3DS is a 55 year
45:13old female history of hypertension,
45:16ulcerative colitis, high blood pressure,
45:18high and pre diabetes who
45:20comes in for routine physical.
45:22Her CBC is pretty much identical
45:25to the the year prior and we'll
45:27point out that she has a high high,
45:30high platelets and a high MCV.
45:34I always think of before I
45:36was a doctor I was,
45:36I was actually a social worker in an HIV.
45:40Clinic and everyone had a
45:42high MCV back then, but.
45:46Otherwise, we don't see it as often,
45:47but we thought that discussing a case
45:51of macrocytosis might be helpful to the
45:54to the participants and the attendees.
45:56So here's the what we have,
45:59we'll go to the next slide please.
46:02Before we turn it over to Anna,
46:03here's a list of her medications.
46:05There is an AC is not AZT or Combivir,
46:10but you can see she is on some medications
46:13for her colitis and a similar question.
46:16To the other two cases,
46:17what other testing or treatment
46:19would you recommend?
46:20And once again,
46:21one is a good time that we should be
46:24sending a referral to hematology.
46:26Alright, Anna,
46:27thank you.
46:29Thanks, Frank. Umm.
46:32So Umm, just to touch on sort of
46:36macrocytosis and macrocytic anemia briefly.
46:39I wanted to start off by saying that,
46:41you know, I think you know as as Bob
46:44Donna mentioned also that the lines are
46:46not so clearly delineated sometimes.
46:49So even though we like to think of anemia
46:50and the three buckets of microcytic,
46:52normocytic and macrocytic.
46:55You know, using just the cut offs,
46:57you know for example an epic
46:59is is not always,
47:00is not always the way to go.
47:02Someone might be slightly macrocytic.
47:04I would still include you know all
47:06the workup that Doctor Bona just
47:07went through for the most part.
47:09Similarly patients who are enormous headache,
47:12I might include workup that
47:13I'm about to go through now.
47:15I think where that doesn't
47:16hold true is that the extremes.
47:17So somebody who's extremely
47:19microcytic or extremely macrocytic,
47:21you know those differentials are are
47:22very different but I think there's
47:24a big Gray zone in the middle.
47:26Umm, in terms of macrocytic anemia,
47:28I think you know two of the the big
47:30buckets that that falls into our,
47:32whether it's megaloblastic
47:33or non megaloblastic,
47:35which really has to do with whether DNA
47:38synthesis is actually being impaired,
47:40megaloblastic anemia.
47:41What we mean when we say that is we see
47:44some characteristic findings both in the
47:46bone marrow and on the peripheral blood,
47:48but just to speak about the
47:49peripheral blood for our purposes,
47:51things like hypersegmented
47:53neutrophils and also macrocytic.
47:56Um,
47:56red blood cells.
47:57These are can be indications that
48:00there is a megaloblastic process going
48:03on or impaired DNA synthesis leading
48:06to ineffective erythropoiesis 2 of
48:08the major causes of megaloblastic
48:11anemia are B12 and folate deficiency,
48:14which could really be a whole
48:16talk on its own.
48:17But you know briefly how we
48:18work this up in the clinic,
48:20the gotos are just serum B12
48:22and folate levels.
48:23I will say that you know,
48:25again just relying on the normal range and.
48:28Epic,
48:28especially in the case of B12 level
48:32is is can sometimes be a pitfall
48:34because for a couple reasons.
48:36Umm, you know,
48:37I sort of consider things in the less
48:40than 400 range to be very borderline.
48:42And though that's an area where I
48:45would always send an MMA to confirm,
48:47I put over here on the right
48:49an image to remind us,
48:50you know why we check homocysteine
48:52and MMA in B12 and folate
48:55deficiency and why we would see.
48:58Elevated you know MO, sorry,
49:00my life just went off.
49:01MMA and homocysteine and beach called
49:04deficiency and only homocysteine
49:06in in in folate deficiency.
49:08But so borderline B12 levels are a
49:10case where I would always send it
49:13also very strong clinical suspicion.
49:15So even with a normal B12 level,
49:17if the story if everything else you
49:19know is really suspicious for B12 deficiency,
49:21I will send it.
49:23It's also worth being aware that
49:25patients with pernicious anemia.
49:28So auto antibodies to intrinsic
49:30factor or to parietal cells
49:33due to actually a lab interference
49:36due to issues with the assay with the
49:40presence of these antibodies can have
49:42a normal serum B12 on lab testing
49:44when they're actually B12 deficient.
49:46So again, if you're suspecting this,
49:49you'd want to check an MA as well, Umm.
49:51And then a reminder that B12,
49:54severe B12 deficiency,
49:55we can see neurologic deficits.
49:58And that's why, you know,
49:59there's the classic teaching that you
50:01know you you want to be cautious not
50:04to treat folate deficiency without
50:06making sure that the patient does
50:08not have concurrent B12 deficiency,
50:10because you could have progression
50:13of neurologic symptoms in that
50:15setting because you're not correcting
50:17the B12 deficiency.
50:18So B12 and folate deficiency can
50:21happen for a variety of reasons,
50:23and I'll go through some of the common
50:25ones between the two of them in a second,
50:26but particular to B12 is pernicious anemia.
50:29She just spoke about PPI,
50:31which can inhibit absorption of B12.
50:34Strictly vegan diet,
50:35as B12 is often found in animal products.
50:39Fully deficiency.
50:40Less commonly seen from a dietary
50:43perspective because at least in the US,
50:46flowers routinely supplemented with folic
50:48acid to prevent neural tube defects.
50:51So it's less common to see this,
50:52but we do see an Alcoholics also in in
50:56patients who have high cell turnover.
50:59For a variety of reasons.
51:00So any patient with a chronic
51:02hemolytic anemia,
51:02including sickle cell anemia or psoriasis,
51:05these would be clinical scenarios
51:07in which you'd be more suspicious
51:10of folate deficiency.
51:11And I in in cases of macrocytic anemia
51:14will pretty much always at minimum,
51:17you know send these two tests.
51:22So just very quickly in terms of causes,
51:25etiologies of both B12 and folic
51:27deficiency with which have to do with
51:30how these micronutrients are absorbed.
51:31So B12 when it's consumed in the upper
51:35GI tract, binds to transcobalamin,
51:37one, goes to the stomach,
51:38intrinsic factor is produced by the
51:41parietal cells of the stomach, binds to B12,
51:44goes into the small intestine where
51:46it's absorbed in the terminal ileum
51:49and then binds to transcobalamin 2.
51:51Absorbed into the bloodstream
51:52and taken up into the tissues,
51:54whereas folate is sort of a more
51:56passive absorption process but also
51:58absorbed in the small intestine.
52:00So for this reason anyone who's had
52:01who has some kind of small bowel
52:04pathology including resection,
52:05whether that be small bowel resection,
52:07bacterial overgrowth,
52:09inflammatory bowel disease,
52:10celiac disease,
52:11these patients are all at risk for
52:13deficiencies of both of these micronutrients.
52:15And then in particular you do have
52:19to consider gastrectomy as a.
52:21Potential cause of loss of parietal
52:23cells and therefore intrinsic factor,
52:26which could also lead to B12 deficiency.
52:31So this is just a very short list
52:34of of an otherwise very long list of
52:37medications that can cause macrocytosis.
52:40The ones I've included here and
52:43many of the medications that that
52:45do this in general actually do
52:47this via a megaloblastic process.
52:50So they actually do interfere
52:52with with DNA synthesis,
52:54which is why we see this macrocytosis.
52:56There are others that can cause
52:58macrocytosis for other reasons,
52:59for example.
53:00If somebody has G6PD deficiency and
53:02develops you know hemolytic anemia
53:04from a medication and can have a
53:07reticulocytosis in that setting.
53:08And and and as Doctor Bonner showed
53:10us particular sites are larger cells.
53:12So a higher percentage of particular
53:14sites increases your average MCV.
53:17But here included are just medications
53:20that through megaloblastic process
53:22can cause an elevated MCV.
53:24And as Frank pointed out,
53:25antiretrovirals for HIV are a common one,
53:29so definitely something that to consider
53:31if you have a patient on HIV medication.
53:34But there's a host of them here
53:36including allopurinol and mercaptopurine,
53:38which the patient in this
53:40question stem was on both,
53:42but also anti epileptics,
53:44bactrum and some other commonly
53:46used medications.
53:50And so in terms of non megaloblastic
53:53causes of macrocytic anemia,
53:54I know we're running short on time
53:55and there's a lot to go through.
53:57But in general, so these are
53:59a means by which causes of of
54:02macrocytosis that don't have to do
54:04with interference with DNA synthesis.
54:06So you wouldn't see those classic
54:09megaloblastic changes like
54:10hypersegmented neutrophils etcetera.
54:12But some of these include liver disease,
54:14liver disease can cause anemia
54:16for a variety of reasons,
54:18some of which would not be macrocytic.
54:21For example,
54:21blood loss or anemia of chronic disease,
54:25but other means which can
54:28lead to macrocytosis,
54:29such as alterations in the in the
54:31cholesterol content of red blood cells.
54:33Also hemolysis,
54:34which could be either from hypersplenism,
54:37portal hypertension or as Doctor Bona
54:40also mentioned on this the review of
54:43different smear findings spur cell anemia,
54:46which in liver disease in particular
54:48is a poor prognostic sign.
54:50You know this site.
54:51We'll consider as guided by history.
54:53So if someone has a history of liver disease,
54:55there's concern by imaging abnormal LFT's,
54:58maybe a low albumin,
54:59a slightly abnormal INR,
55:00any smear findings that could be consistent?
55:03You know,
55:04those are the situations where I would
55:06consider that liver disease could be the
55:08cause of the underlying macrocytosis.
55:10Alcohol use certainly can lead to
55:13macrocytosis and this can actually
55:16take months to resolve after the
55:19patient ceases to consume alcohol.
55:21It's always important to take an alcohol
55:24history when working out these patients.
55:26As I mentioned increased reticulocytes which
55:29are larger cells and mature red blood cells,
55:33a higher percentage of reticular sites in
55:36the peripheral blood increases the MCV.
55:38So this is always something to
55:40consider like any anemia should be.
55:42You know,
55:43one of your go to 1st test is a
55:45reticulocyte count and if elevated
55:47you have to consider whether there
55:48could be an active, you know,
55:50a bleed, but more likely.
55:52You know,
55:52if this patient is really macrocytic,
55:54some kind of hemolysis and you'd want
55:56to send sort of a hemolytic evaluation.
55:58So LDH, haptoglobin,
56:01direct bilirubin,
56:02total bilirubin and a peripheral smear
56:05hypothyroidism can also lead to macrocytosis.
56:08You know, I,
56:09I do send this very often in these workups,
56:11but I think this also should
56:13be guided by history.
56:14I think it would be unusual to see
56:16somebody with a macrocytic anemia from
56:18hypothyroidism without otherwise having
56:20other signs and symptoms of that.
56:22Um copper deficiency can cause
56:24anemia of pretty much, you know,
56:26any size red blood cell.
56:27But again, as guided by history,
56:29if someone has some kind of absorptive issue,
56:33dietary deficiencies for other reasons
56:35or zinc toxicity and you know,
56:38one of the sort of curls is
56:40somebody who's using a denture glue
56:42that contains zinc, you know,
56:44which can paradoxically cause
56:46copper deficiency.
56:47Again,
56:48I don't routinely send this just
56:49if it's a high clinical suspicion
56:51or an otherwise totally negative.
56:52Uh, work up monoclonal gammopathy.
56:55So as Doctor Bona talked about two.
56:57So my threshold to send this for
56:59macrocytic anemia is very low.
57:01I'll send it on pretty much anyone unless
57:03there's a very clear clear cut reason.
57:06You know why they have a macrocytic anemia.
57:07So that includes not just the spec but
57:10as Doctor Bona said the Immunofixation
57:12and the the free light chains.
57:15And this can be even in the
57:17absence of other crab criteria.
57:19So even if you know the the
57:21renal function is normal,
57:22they have no Bony pain calcium.
57:24Normally I would still send it.
57:27And then macrocytic anemia,
57:28the last thing I'll say I think is that
57:30you know even more so than the other,
57:32you know Norma acidic or
57:34or microcytic anemias.
57:36The clinical suspicion for an
57:38underlying bone marrow process or
57:40malignancy has to be you know quite,
57:42quite high and the threshold to refer
57:44to hematology very low because we
57:46wouldn't want to miss something like
57:48an MGS or an under other malignancy,
57:50especially if this preliminary workup
57:52which is all pretty easy to obtain
57:54is negative or especially in the
57:55case where there are concurrent.
57:57Utopias with thrombocytopenia or
57:59leukopenia any other, Umm, you know,
58:02symptoms which might be concerning,
58:03but you know,
58:04the bottom line being that if there's
58:06no clear reason for macrocytosis,
58:08whether it be medication,
58:10A B12,
58:10folate deficiency or any of these
58:13other things that you know,
58:14the threshold should be very,
58:15very low to refer to hematology
58:17for further workout.
58:24Good. So I'll take the
58:25liberty of just asking the two
58:27final questions and then
58:29we'll we'll wrap up.
58:31So I'm doctor Zarkov power ask
58:33again about frequency of B12 level
58:36whether it should be continued
58:37to be checked in patients on a
58:40bike rides and at what interval?
58:44Oh yeah. So good question.
58:46So I'm like on metformin.
58:49So that's a good question.
58:51I don't know that I really
58:52know the answer to that.
58:54My suspicion would be you know,
58:55as long as the patient is
58:57continuing on metformin,
58:58if they develop B12 deficiency on metformin,
59:01I would probably just keep them on B12,
59:04you know, now and then you know
59:07you could check a serum level and
59:09see if it's responding every,
59:11you know, six months.
59:12So obviously most patients are on
59:14metformin for years and years.
59:15I don't know that there's a clear
59:18clear cut guideline for how often.
59:19Repeat that,
59:20but I would probably just
59:21leave the patient on it.
59:24And then Doctor Reeve asks patients,
59:27especially seeing naturopaths
59:29bring in reports of their
59:32methyltetrahydrofolate reductase testing.
59:35And the question is how?
59:38How much do they need this very
59:40special form of folate that's
59:42often prescribed for them if
59:44they've been asymptomatic?
59:46Yeah, no, I'm not aware of
59:48there being any data, you know,
59:50to support that at all.
59:51You know, somebody has fully 50.
59:55Folic acid usually use in one to two
59:58milligrams per day orally as well.
01:00:01It's very orally bioavailable,
01:00:04you know, people will respond to that.
01:00:07So no, I'm not aware of there being
01:00:09any data that any other formulations
01:00:11would be necessary in the setting of
01:00:13fully deficiency and especially not,
01:00:15you know, if there's no fully
01:00:16deficiency. OK.
01:00:17And now one final question.
01:00:21Like iron, I understand that the B12
01:00:24orally is actually more effective
01:00:26than we've given it credit for.
01:00:28We have a lot of people
01:00:28who are on injections.
01:00:30What is your threshold to cross
01:00:33over from oral to injection?
01:00:37So, you know, I think it it depends
01:00:39on the severity of the deficiency
01:00:41and also the D so for example,
01:00:44not that any of us really see
01:00:47this anymore or or often,
01:00:49but if somebody were to present to you
01:00:52with neurologic symptoms for example,
01:00:54that's somebody you'd want to
01:00:55I am injections right away.
01:00:57You wouldn't want to wait you know
01:00:58for an oral supplement also if it's
01:01:01somebody who has B12 deficiency
01:01:02for a malabsorptive reason either
01:01:05because of a gastric bypass surgery.
01:01:09Permission, yeah,
01:01:10they're not going to respond
01:01:12to PO supplementation.
01:01:13So those patients need to be on,
01:01:15I am probably lifelong,
01:01:17but otherwise in somebody who has
01:01:19bowed pathology who has no reason
01:01:22to not be absorbing it orally.
01:01:26PO B12 is very effective, you know,
01:01:28usually 1000 micrograms daily. Good.
01:01:32Well, I the pace kind of picked up
01:01:34at the end and I apologize for my
01:01:37time management that didn't have
01:01:39us a little more evenly spaced,
01:01:41but tremendous gratitude to
01:01:43all of our panelists.
01:01:45This was really terrific information.
01:01:47Like Frank, I was part of the
01:01:50preparation and still learned.
01:01:51So there were a lot of both,
01:01:53you know, very practical tips here the
01:01:57upcoming speakers are demonstrated,
01:01:59you know on the slide.
01:02:01Here we do not have a talk in January.
01:02:05It's just a little early in the
01:02:07month after the holidays to do that.
01:02:10So please join us and if you don't mind,
01:02:13please stay on.
01:02:14There will be a very quick survey
01:02:16at the end in order to.
01:02:19Just make sure that we get your
01:02:22feedback to help us in the future
01:02:24so Anne Chang couldn't be here.
01:02:26But on behalf of Anne and myself,
01:02:28we thank you so much for
01:02:29your attendance and again,
01:02:30thank you to our panelists.
01:02:34Goodnight. Thank you. Goodnight.