John Kelton, MD identifies anemia secondary to iron deficiency as the most frequent hematologic complication during pregnacy and explains treatment options.
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it is now my pleasure to introduce Dr John Calton, professor in the Department of Pathology Molecular Medicine and Executive Director Michael G. De Groot Initiative for innovation in healthcare at McMaster University, who will speak on human technological problems of pregnancy. Dr. Colton is a good friend of this conference who has participated in our conference many times and is always enthusiastically received. Please welcome Dr John Calton. If you have questions you would like to have him address, please use the ask a question chat function to ask your questions during the presentation. Questions will be addressed during the panel session. Thank you for inviting me to again participate in a very different session, but I'm honored and delighted. Uh, I've had a chance to meet with this group for many years and this is a different way of meeting. Conflict of interest, Sad to say, still no consultancy. Still no boards, but I keep my fingers crossed now. I've only got 30 minutes. What do I do? Do I leave out important content? Because I love the historic Tropic trivia. What to do? I know. Let's go with the trivia but on the fair to make it fair for important stuff. I'm going to let you know this is important, since I've got three or four main points I'd like to convey today. But first, I've got to give an editorial comment. Oftentimes, my American friends are telling me how fabulous Canadian healthcare is and how much they want it. My head could explode. Sorry. As of this day, I haven't been vaccinated against Covid. Nor has my daughter, a personal support worker. Nor have many of my physician colleagues. And it is a very complicated reasons why Canadians are not being vaccinated. But I'll just say, uh, it is frustrating. Anemia in pregnancy is very common, but first it's important to emphasize that in actual fact, every woman is anemic by physiological definition. The plasma volume expands, the hemoglobin expands they never quite match so that you're always anemic so that we will accept a normal hemoglobin of 10 to 10.5. In fact, a high hemoglobin is curious. It's only at low hemoglobin levels under 60 to 80 or 68 that adverse outcomes begin to happen as long as the hemoglobin is above 80 there is minimal adverse effects on mom or her baby iron deficiency iron is by far the most common element on Earth. Yet it is by far the most common deficiency in humans, and that explanation is a long and complicated one that I'm not going to give today. But another time we'll talk about it in the initial trimester. You need a milligram of iron a day. By the third, you need a lot more 30 to 30 mg of iron per day, about a quarters it's absorbed. Can you get that by diet alone? Well, it turns out you would need between a pound and a half a beef or 4 to £5 of chicken. Well, think about that in a second. I've been struck. How often? Pekka is a symptom, and many of the women are actually embarrassed that they have Pekka most frequently Pekka for chewing on ice. Sometimes spaghetti or restless leg syndrome is common, but can you do what many women would like to do? And that's replaced their iron by food alone? Well, about a year or two ago, Canada permitted Popeye's chicken to be imported into Canada. Now it took years of study, and I wondered how many Popeyes would I need to eat to have 4 to £5 of chicken in me. Turns out it's between 25 30 and that's not including the delta sauce or the pickles. So therefore, almost every woman now is recommended to be supplemented. There's a few unusual exceptions, but most need supplementation of 30 to 60 mg of iron per day. How do you get that heme iron Pro Ferrin is very well tolerated. It's from him. It is modestly, well absorbed. Uh, I have found that it is, well, well tolerated, but it usually doesn't work well. Most of us now use policy acrid irons and some of the old iron elemental irons that are not expensive. But they have to be taken with food or with orange juice. There is a change, and this is my first thumbs up. There is a change in thought, almost for sure, because of helps Eden. It is necessary to take, or it is an advantage to take the iron every other day. That's a unexpected to me. And when that information started coming out the last three or four years, that, in fact alternate day iron was better absorbed than everyday iron or, God forbid, three or four times a day iron. It turns out that that's related to the rise in Hopes Eden and then, in turn, the reduction in absorption. How do you diagnose it? I think the gold standard still fair written less than 30 is iron deficient. But many people who are maternal fetal experts would say less than 50 there, almost for sure, highly sensitive and highly specific. Remembrance. An acute phase reactant. Sometimes you need the percent saturation. Less than 20% mean crepuscular. Volume is not nearly as useful a diagnostic test because the red cells increase in size at the same time the micro psychosis drops, the size helps. Hidden, I'm going to say, is too soon to know. But remember, helps Eden Sheraton are acute phase reactions. Parental iron. That is something that is happening quite a bit over this past five years. As more and more iron carbohydrate preparations are available, most people would now use parental iron at a much more liberal way than they did five, certainly even 23 years ago. Uh, in Canada, most of us use Vienna Fear fair because it's available, but you require more doses. There's a number of new iron carbohydrate compounds that are now being evaluated, and I think the recent trends would say more people are airing on the side of giving parental iron sooner rather than later. Of course, don't be nervous in the third trimester. If the hemoglobin is down under 78 80 most people would recommend blood transfusions for a better fetal outcome. Now, trivia time. Okay, the story of vaccinations actually goes back farther than any of us would have guessed. Smallpox has been a catastrophic panda pandemic for essentially human history. It carries a case fatality rate of greater than 30% and it is incredibly infectious, with extraordinarily high our numbers. Who would have thought we would all now know what in our number means? Our story starts in Greece, and it starts 2500 years ago and there through cities, a physician observer said. Those people who carry the marks of the plague and remember that small parks leaves you with scars. Lifelong scars. Those people who carry the marks of the plague can care for those can be with those who in fact, have smallpox. In other words, this was the first time humans understood that exposure, real or induced, can give long lasting protection. This is a concept that took another 2000 years for people to better understand it. Macro Citic anemia, in my experience, is very uncommon. Remember the M C D increases by 5 to 10 in pregnancy because of Aretha poet sis, possibly also because of changes in the liver. I think, uh, there's debate about that, and it's not terribly well studied. All of us know macro acidosis. We think alcohol, liver disease, less commonly, B 12 and folate. It is difficult to get B 12 deficiency or folate deficiency, and I'm going to cover these very quickly for you. But we'll just say it's not a high frequency problem for my investigation. I'm going to organize a direct anti global in test. I want to rule out autoimmune hemolytic anemia, a measure of B 12, and I want to measure a foliate. The best foliage, of course, is red cell folate. But increasing labs no longer do that. And why don't they do it? And it turns out that folate is now very uncommon because in western society virtually all grains are full. It fortified, making this a very uncommon deficiency. B 12 is uncommon. Once it was generally said that if you had severe B 12 deficiency, you could not be pregnant. And the rationale or the explanation for that was you need B 12, especially for cell division nuclear division. And that was felt to be sterilizing. And certainly today, in infertility clinics they study, or they give B 12 as a treatment for infertility. As we all know, B 12 deficiency is very difficult to have because of body stores. It has a slightly it has a later on set, but we are seeing it more and more in Crohn's disease increasingly in bariatric surgery. And, in fact, at least a third of people who undergo bariatric surgery will have low B 12 proton pump inhibitors are recognized as being associated with a drop in B 12 level. But how frequently this becomes so severe as to cause of frank deficiency, I think, is uncertain. It's certainly well described in case reports. How do you treat treat with folic replacement? Which, of course, is in the maternal vitamins and B 12 micro micro amounts of B 12 are in the maternal replacements. And if they have a G I, uh, abnormality. Most people recommend B 12, if not potentially. You would give it some sublingual e uh, to get absorption. Remember that a milligram of B 12 actually can push across mucous membrane barriers without needing intrinsic factor. Now it's time to get into the meat. This is a typical consult. Ms. W J. 32 year old G one p 0 32 weeks has a platelet count of 38,000 common common consult. What do you do? Well, let's think about Trauma said Opinion, pregnancy and without any undue modesty. I think that the best study was one that happened many years ago. Uh, when I had less white hair and my dear buddy Bob Burrows and I did this and we just took a whole lot of ladies prospectively presenting to McMaster o B G y n unit, and we found that the vast majority had something that we called incidental. It's now more commonly called gestational thrombosis. Dapena etp was about 1 to 5% prayer clamps at 15 to 20% help fatty liver, 1%. I'm not going to be talking about the pre eclampsia, fatty liver disorders. I think that I need another 15 minutes for that. And then pregnancy. Unrelated is I t P and anti phosphor Lipid secondary. I tp Lupus. Uh, thrombosis. Homicidal Penick Popara and drug induced thrombosis. Dapena? Uh huh. So you're called to see this patient, and you are going to do what we all do. And that is in our mind. We're using our roller dex to, say 38,000 platelet count. She's not leading. What is her problem? Well, the most important test right off the bat on the phone, you say, is what's her blood pressure. Even 100 and 25 over 85 in pregnancy is a signal that that woman could be getting preeclampsia. Remember that the blood pressure through vaso dilation drops in pregnancy. Is she him a statically intact? Well, at that platelet count, she's going to be you Order CBC liver functions, thyroid direct anti globulin test anti nuclear antibody in Antofagasta. Lipid viral will have been done, of course, as part of the pregnancy. We like doing an H. Pylori. I'm aware that not everybody does that, and there's some shifting recommendations about that. And finally you could do bomb will, er, brands, uh, for thrombosis, that opinion, pregnancy. But that's pretty fine point. I'm going to say you do the platelet count and on repeat their 40,000, I would emphasize that a repeat platelet count is very important. More and more up in Canada, no one looks at the blood Fillmore's just looked at quickly, and the CBC might be done at an outside lab. You need someone to have looked at the platelets, make sure that they're not clumped. You want to make sure, Of course, there's no fragmentation. Certainly rare, but TTP less commonly H. U S can present in pregnancy on this woman. All are normal. Blood pressure is normal. There's no history of meds, no drugs, no bruising, no added apathy. And this is a very common situation to find yourself in this woman. Almost certainly. Mathematically, 90% plus has incidental thrombosis. Subpoena or itp. How do you separate the two? And this is a common but important separation, incidental or gestational is late in pregnancy. I tp can be any time, certainly can first present in pregnancy history. No. Yes. Platelet count, by definition, is above 80,000 with incidental or gestational trump aside opinion and and I. T p. It can be anything. The maternal risk and the fetal risk is zero. So stop your investigations with incidental you'll you'll kick up something that you don't really want the actual risk of I t p for Mom and Baby is modest and again, that's important to emphasize. So with her platelet count, she we've ruled out the possibility of incidental because the platelet count simply too low and all of the other tests came back. She's got it cheap. We're gonna move forward to 37 weeks now. The platelets are down to 22,000, which typically they do do the platelets in at least 40% of it. Deep drop across the pregnancy. She's a symptomatic and she wants an epidural. You have two options. One is pregnant. Zone one is I D I G. I happen to like the use of I dig because it's almost diagnostic. If her platelet count bumps up, then she almost certainly has immune thrombosis. That opinion. But here and is the problem for I V i g. You get a rise in the platelet count, typically of 2 to 3 weeks in about half the people. But what do you do if she doesn't go into labor? And the platelets have peaked at 150 and they're on their way down as they 100% always will do what we say to our the woman And we say to our obstetricians will say at that time she is going to be 40 weeks. We can keep the platelets up. Why don't you? Are you prepared, Mrs W. J. To be induced because you have that window? And if she's not going to go into into labor, you're either going to have to re give her I V i g. Or have the platelet count fall. That means that many patients we would just go with prednisone to boost the platelet count. What happens? Well, this is a retrospective study by sun, but it's a good study. Uh, and they gave like many ITP patients, no treatment was needed. Bye. Random luck. Almost half got pregnant, so almost half got I v i g. And the response rate was the same. We have seen this response rate. Always remember that I v i g has got up 60% as does prednisone. And it seems in pregnancy that many people with their ITP seem to be more refractory. And that stuff say, essentially the same adverse effects. Mhm. So how do you manage these patients? I think mild to moderate. Just hang. Hang in. We would probably give Ivy or prednisone, as we said at term, but a routine delivery. There is no hem, a static advantage in cesarean section, but drugs, attrition. So make that decision for severe thrombosis. Dapena. We would recommend I V i g across the pregnancy. I don't think splenectomy is ever indicated. Most people would strongly avoid prednisone in the first trimester because of cleft risks of cleft palate, which is uncertain but still nonetheless realizing. And since this is the grand old United States with your litigation system, you want to avoid those kind of situations. Uh huh. It's time to slightly change the subject vaccinations. So the Greeks had discovered that if you were exposed and had it, it didn't come again. It was either in China or India or in the Middle East, and with the silk and spice trade. It was not known where it was But smallpox pustules were scraped out, crushed in a pedestal or dry, heated in some countries. And then they were put up the nose or a scratch was put on the skin, which triggered a minor case of smallpox but seemed to give that person considerable benefit. The problem was dozing so that some people would have this done, and they would have a full blown case of smallpox back to ITP. You're limited in what you can do in pregnancy. Approved her steroids, Ivy League Contra indicated, are a number of medications or not recommended. There's some interesting data coming for to Po, and it is important to emphasis that it is not approved for use in either of our countries. In pregnancy, it does cross the placenta. There's now two studies happened, including one within the past two months retrospective, observational. But they're starting to become big enough. This one, plus the previous one, puts us towards 30 to 40 women that had minimal adverse effects and as we know, it does raise the platelet count in about 75% of women. Interestingly, one child had neonatal trauma psychosis, so I think, recognizing despite non approval, there could be some interesting opportunities happening in the future. Pregnancy in I. T. P has a good outcome for the mum. Don't say to them, um, you should not become pregnant. Let them. They're going to decide if they want to. But the vast majority nothing happens. One third to one half need treatment. Depends how aggressive you are. Most of the fetuses are just fine. It is uncommon to have a very severe thrombosis. Dapena. About 1% of the babes will die, and this is consistently right from our study and coming through. Uh, remember, you want to do a cutaneous or umbilical sample at delivery. That baby's platelet count if it's 30 is going to keep on dropping over the next few days. But the the neonatologist will know that the big conceptual breakthrough happened in the 17 hundreds, and by then with trade, smallpox was all over the world. It was in Turkey, where they were doing scratches and giving the ground up smallpox that it was shown to be quite beneficial. And Lady Montague, the wife of the ambassador visiting Turkey, brought the technique back to England. Mhm. I'm going to just finish with pregnancy anti fossil lipid syndrome, which is a probably the most important, dangerous thing I've talked about right now. It has criteria. The Sapporo Sydney criteria greater than one fetal death or a couple preterm or preeclampsia or placental insufficiency or repeated pregnancy. Early losses. You suspect it clinically, Cyril. Logically, all of us now do three tests, and a triple positive is associated with a very poor fetal outcome. And it's in fact, a graded risk to that fetus. With the Lupus anticoagulant carrying the highest risk. There's two issues. One is the fetal loss, and the others vita e venous thrombosis embolism. Arterial thrombosis embolism. Remember, a normal pregnancy carries a significant, uh, risk of venous thrombosis embolism that is increased at least 10 fold to 50 fold in a woman who has anti phosphor lipid syndrome. Here's three situations you face number one. There's no history, but you find in any thoughts Philip at anybody. This is a not rare situation in our hands. They are recommended to be monitored. I and my partner, Dr Arnold, almost always use aspirin in these women because they are very nervous, and if they lose this fetus, they will be very concerned. So even though uh, that's not been shown that aspirin benefits this particular situation, we would recommend it. The situation more commonly seen are frequently seen is Andy Foster Lipid and a previous P T E R A. T T. And these women should be managed, as you would guess, with therapeutic low molecular weight heparin, an fractionated heparin at delivery, possibly also including low dose aspirin. And finally, what about the woman who comes in with anti fossil lipid and pregnancy losses? There is good study showing aspirin at low dose or what we would call intermediate dose. Now many people give intermediate dose is beneficial. Most would also give low molecular weight heparin, which is our practice at McMaster. But it's important to emphasize that, actually, the results are somewhat mixed, and some studies have been positive. But the largest meadow in that meta analysis did not show increased fetal outcome. Nonetheless, we would almost all do it anyway, and you've got about a 70% to 80% live birth chances. Mhm. The breakthrough happened in the 17 hundreds, and again it was an observational biologist who noted that milkmaids on their hands they got blisters almost identical to smallpox blisters. And then something very strange happened. Those individuals who had the the cowpox, in fact, did not get smallpox. This is from the 18 hundreds after Jenner made this observation. This is from France, but it shows the circle of a scientist physician at the time looking at the young woman's hands, seeing the cowpox and the other, noting that they came from the cow, utters and saying, These two seem to be linked. Edward Jenner in 17 96 took variola, which is Latin for a pimple from a Vaca, which is Latin from a cow and injected it into a child and began to inject it into more and more people and showed that it was possible to in fact prevent many episodes of smallpox in a process that subsequently became vaccination. So a wonderful story and an incredible example of how we as scientists, clinicians build on previous observations. Thank you for inviting me Special thanks to Michael cost Carrie Bence, Denise Manalo. I'm delighted to be here and just before I say goodbye. Thank you for your attention. And please, if you gotta just one little vial for me said no. Send a couple up to Canada. We could use a few million. Thank you.
