Smilow Shares with Primary Care on Anemia

Transcript

• 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&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.