Probable AA diagnosis - confused

[kirag1964]

Hello!

I am 52 years old, and in the process of having my bone marrow failure diagnosed. Many of the signs point to AA. However, the hematologist who I was initially sent to says I am more complex than he feels competent to deal with (I'm "over his pay grade"). So they are not able to complete the diagnostic process and/or discuss treatments, so I am now in limbo waiting to be seen by a specialist at UPenn hospital. (Is it normal to be transferred mid-stream because of the rarity of this?)

I know I should probably just be patient and wait for clarity from the medical professionals. However, I am frustrated and a bit scared, and since my current hematologist can't answer my questions (I asked about my reticulocyte levels which is when he made the "above my pay grade" comment), I am confused because some of my blood levels do not seem to fit the picture in a way I can make any sense of. I was wondering if any of you can help me make some sense of things.

My story so far:
I had a routine physical about a month ago and a few days later got a call from my doctor saying all my counts were low. Subsequent blood tests have confirmed this. This is a summary of my counts from the multiple blood tests I have had in the past few weeks:
WBC - 2.8-3.3
RBC - 2.1-2.21
Hg - 7.3-7.9
Platelets - 25-41
My red blood cells are also slightly macrocytic. Folate and B12 are normal.

I had a bone marrow biopsy and my bone marrow is quite hypocellular. My cellularity is 10%, which I gather is much lower than it should be (I should be at about 40-50% given my age). No blasts in my bone marrow. However, the rest of what is on that report is very confusing and my current doctor really wouldn't go over it with me.

Both the pancytopenia and low bone marrow cellularity point to AA - and I think a number of other possibilities have been ruled out.

However, this is really confusing me:
- despite having very low marrow, and low RBC count, my reticulocyte count in my blood is 75 which is in the normal range. This makes NO SENSE to me (how is my insufficient bone marrow pumping out a sufficient number of baby RBCs) and seems to totally not fit the criteria for AA. My doctor could not offer any explanation except to say that my "normal" level was actually "low" because with such a low RBC count he would expect my level to be high (???)

Can anyone offer a possible explanation?? Obviously my new doctor will go over everything and perhaps order new tests as well, but right now I don't have an appt until April 18th. They are hoping to move it up, but the doctor is currently out of the country and I am not sure when they'll be able to fit me in.

We believe that this snuck up on me over time, so while I am feeling pretty wiped out I am still functional. The worst symptoms for me are the anemia ones - feeling shaky, heart racing, out of breath from climbing one flight of stairs, blood rushing in my ears. I have always been super healthy (just signed up for a 10-mile run in May ) so I am very frustrated with not feeling well.

I know that you can't diagnose me, but any insights or expressions of support would be much appreciated.

[bailie]

I had a similar first experience. I had a CBC on a Friday and they sent me immediately to our premier hospital in Oregon (Oregon Health Science University). They had me have another bone marrow biopsy and diagnosed my MDS. Your situation could be anything from not too serious to something that needs close attention. Having no blast cells is great. You will find out more when you see the new doctor. I am surprised that there isn't another doctor to see at UPenn. You should probably have another BMB a couple of weeks before seeing that doctor. There are so many variations with these blood diseases. We wish you the best, keep in touch.

[Marlene]

Is there a reason why you are not getting a red cell transfusion at this point. Your HGB is pretty low. Most have a transfusion threshold of 8. Getting your red cells up will help a lot.

Don't worry about the cellularity at this point. For SAA, the BMB is one way to rule out blood cancer and MDS. SAA is diagnosed once everything else is ruled out. And for some reason, people with low cellularity can still produce normal peripheral blood counts. Sometimes, it's just because they tapped a dry spot in the marrow.

It's good see a doctor who has experience with SAA. Very few hematologist ever see SAA in their lifetime and experience with this disease is a must.

[kirag1964]

Originally Posted by Marlene

Is there a reason why you are not getting a red cell transfusion at this point. Your HGB is pretty low. Most have a transfusion threshold of 8. Getting your red cells up will help a lot.

Originally Posted by Marlene

It's good see a doctor who has experience with SAA. Very few hematologist ever see SAA in their lifetime and experience with this disease is a must.

What my doctor told me is that they base transfusions on symptoms, rather than numbers. I've been relatively asymptomatic for someone with such severe anemia (as I said I am generally very healthy and take good care of myself), although the anemia symptoms have definitely gotten worse the longer I've been in the 7's. I can feel how hard my heart is working. I also think I may have downplayed things a bit. I have good days and bad days, and I try to focus on the good days - but that may mean I am not letting him know how awful I feel sometimes.

He also said that they don't generally treat AA with transfusions, which I believe is incorrect. But a good reason to be seeing someone else ASAP! The doctor I am being transferred to is actually one of only 4 doctors in PA who is listed on the MDS/AA website, so that is very good news. I just hope that I can get in there soon.

At this point I don't think my current hematologist wants to do anything with me at all. He answers my questions, and he will continue to monitor my CBCs until I am with the new doctor, but I get the impression he is nervous about treating me since he is so unfamiliar with this. He feels out of his depth, and doesn't want to "experiment" on me. He said the last time he saw an AA patient was when he was a resident - and he's in his 60s! This is at a very busy and well-regarded suburban hospital near Philadelphia.

[Marlene]

Well you certainly do have symptoms due to low HGB. And even though transfusions are not a curative treatment, they are a vital part of the overall care. You will feel like a new person when your HGB is higher.

You may want to consider another local hematologist to provide your immediate supportive care if you are not confident in the one you are seeing now. Even if a doctor is unfamiliar with SAA, there is nothing stopping them from consulting with the NIH which has treated many with SAA. They would be a good resource for any doctor. You may want to pursue going the NIH for a consult. I'm surprised that it will take a month to get you in to see someone.

Some other things to consider while you wait:

Nutritional issues - B12, Folate, Iron, copper, zinc and vitamin D are heavy hitters. You should have all checked. Even though your doctor said your B12 was normal, many consider a low-normal okay. But more recent thinking says a B12 serum should be at around 500. A better indication of B12 deficiency/insuffiency is to check your MMA and homocystiene levels. Your GP can order the nutritional test.

Digestive issues - If you are on an acid reflux drug, this can prevent your body from absorbing nutrients. Also, h.pylori bacteria has been implicated in BM diseases. This the bacteria that causes ulcers. You can get screened for that. Your GP can check it for you. Celiac disease or gluten sensitivities can cause anemia too.

Bleeding issues: I assume your doctor ruled out any bleeding issues. Easily checked with a urine and stool test to check for blood.

Medications: Meds can cause BM suppression so check all meds, if any, that you are on. Statins can impact it.

[kirag1964]

Marlene - thank you so much for all your helpful suggestions! I think bottom line they are really hoping to get me into Penn a LOT sooner than 4/18 (like next week at the latest) - and that may be the case. The fact that this doctor is traveling + the stupid storm we are having today is holding up our ability to make that happen. Penn does have all my results and slides, so hopefully once things settle down and the doctor returns, I will get an appointment.

But if that doesn't happen you have given me a good list of things to investigate and follow up on!

I am on absolutely no medications (just vitamin D), and in fact have never been on a medication for longer than a week or two in my life. Apparently the pathologist thought it looked like a drug reaction, but unfortunately we can't explain my low blood counts that way!

[Hopeful]

Originally Posted by kirag1964

However, this is really confusing me:
- despite having very low marrow, and low RBC count, my reticulocyte count in my blood is 75 which is in the normal range. This makes NO SENSE to me (how is my insufficient bone marrow pumping out a sufficient number of baby RBCs) and seems to totally not fit the criteria for AA. My doctor could not offer any explanation except to say that my "normal" level was actually "low" because with such a low RBC count he would expect my level to be high (???)

Can anyone offer a possible explanation?? Obviously my new doctor will go over everything and perhaps order new tests as well, but right now I don't have an appt until April 18th. They are hoping to move it up, but the doctor is currently out of the country and I am not sure when they'll be able to fit me in.

Hi kirag1964,

I am not a doctor or in the medical field but may be able to provide some insight to your question...

Having a normal ARC is actually a very good thing. Dr Young published a study awhile back that showed that people with a normal ARC (or ALC) were more likely to be responders to immune suppressive treatment (IST) for their SAA. My understanding is that a normal ARC means that the stem cells are still capable of pumping out a bunch of immature red blood cells (i.e. the factory is still working). However, if you have an active immune attack going on, it may be destroying them just as fast.

Don't wait a month to see a specialist in AA. Be a squeaky wheel. More favorable responses to treatment are achieved within 30 days of diagnosis. An AA specialist knows this and will try to accommodate you in their schedule.

Have you been tested for PNH?
How is your ANC?

Also, check out the videos put out by AAMDSIF to get the latest encouraging news about diagnosis and treatment:
https://www.pathlms.com/aamdsif/categories/363/courses

Good luck!

[Neil Cuadra]

kirag1964,

I'd like to point out that your current hematologist deserves credit for letting you know that, without more experience, he can't answer your questions and that he can monitor you but shouldn't treat you. Some physicians would let ego get in the way of such honesty.

He did you a great favor by indicating that a specialist needs to evaluate your condition, address your questions, and recommend your treatment. I hope you get answers soon.

[kirag1964]

Originally Posted by Hopeful

Hi kirag1964,

I am not a doctor or in the medical field but may be able to provide some insight to your question...

Having a normal ARC is actually a very good thing. Dr Young published a study awhile back that showed that people with a normal ARC (or ALC) were more likely to be responders to immune suppressive treatment (IST) for their SAA. My understanding is that a normal ARC means that the stem cells are still capable of pumping out a bunch of immature red blood cells (i.e. the factory is still working). However, if you have an active immune attack going on, it may be destroying them just as fast.

Don't wait a month to see a specialist in AA. Be a squeaky wheel. More favorable responses to treatment are achieved within 30 days of diagnosis. An AA specialist knows this and will try to accommodate you in their schedule.

Have you been tested for PNH?
How is your ANC?

Also, check out the videos put out by AAMDSIF to get the latest encouraging news about diagnosis and treatment:
https://www.pathlms.com/aamdsif/categories/363/courses

Good luck!

Thank you so much for your response! That is very encouraging. I am good at being a squeaky wheel (lots of practice from having a kid with intractable epilepsy), and will keep pushing for an appt. I think that the main issue has been that Dr. Luger has been out of the country - and she may have been further delayed by yesterday's weather. Hopefully once she is back and has a look at my information they'll get in touch with me.

I do not think I have been tested for PNH. Would that be consistent with pancytopenia, or would I just have low RBCs/Hg?

The ANC is not a number that has been given to me in that form, but I think it is the same as the absolute # of granulocytes (is that correct?). If that's correct then my ANC is good because while my overall WBC is a bit low, that seems to be due to low normal monocytes and below normal lymphocytes, while my granulocytes are 2.0 (in the normal range). Again - I have no idea what all this adds up to but that's what my CBC says!

Hopefully some answers soon! I'll keep posting here as things progress. And again - thank you so much!

[kirag1964]

Originally Posted by Neil Cuadra

kirag1964,

I'd like to point out that your current hematologist deserves credit for letting you know that, without more experience, he can't answer your questions and that he can monitor you but shouldn't treat you. Some physicians would let ego get in the way of such honesty.

He did you a great favor by indicating that a specialist needs to evaluate your condition, address your questions, and recommend your treatment. I hope you get answers soon.

I totally agree, and I appreciate his honesty! I don't want to be his experiment either LOL!

I had absolutely no idea how unusual my presentation was until he told me he had last seen this when he was a resident! And my Primary Care doctor said he has never seen a case of AA in 25 years of practice. So I am very happy to be transferred to someone with more expertise - I just wish I could get in there today or tomorrow!

[Neil Cuadra]

Originally Posted by kirag1964

I had absolutely no idea how unusual my presentation was until he told me he had last seen this when he was a resident!

When my wife was treated for aplastic anemia, she was the only AA patient in the major Southern California treatment center. After she was diagnosed with MDS, it was over a year before she met another MDS patient. It's no wonder you have to hunt to find specialists with experience treating these diseases.

[Hopeful]

Hi kirag1964,

ANC is Absolute Neutrophil Count and is an important number to track - even more so than WBC. Your ANC will tell how susceptible you are to infections. A low ANC is also one of the criteria used in diagnosing the severity of AA, should that be what you have.

Sometimes you will see PNH and AA together. Studies have shown that people with a small (subclinical) PNH clone are likely to respond to IST.

[triumphe64]

Originally Posted by Neil Cuadra

kirag1964,

I'd like to point out that your current hematologist deserves credit for letting you know that, without more experience, he can't answer your questions and that he can monitor you but shouldn't treat you. Some physicians would let ego get in the way of such honesty.

He did you a great favor by indicating that a specialist needs to evaluate your condition, address your questions, and recommend your treatment. I hope you get answers soon.

You are so right.

[kirag1964]

Thanks everyone!

I heard from UPenn this morning - they finally got all of my labs and slides from Abington Hospital, and I am getting in to see Dr. Daria Babushok there tomorrow morning. She is one of only 2 doctors there with experience with aplastic anemia (they are calling that the "likely" diagnosis), so I feel lucky to get in there.

I honestly do not think that my AA (if that's what this is) qualifies as severe at the moment. In fact, my platelets recovered slightly at my last blood draw - they were at 45 up from a low of 29 - and everything else is staying pretty stable. I don't expect to walk out of there tomorrow with a firm diagnosis, but hopefully at the very least she can answer some of my questions and give me a sense of what to expect.

Thanks again everyone - you guys are a great resource! I'll post again after the appointment.

[kirag1964]

Saw the doctor yesterday and she was amazing! Knowledgeable, patient and caring. I really liked her and feel extremely grateful to live just 25 minutes from an expert on bone marrow failure. I am definitely in good hands. And to those of you that said it was worthwhile to wait for someone who understands these diseases - you were so right! Like night and day!

She thinks it is very likely AA - not only am I pancytopenic, but my marrow is very hypocellular, and much of what is there is lymphocytes not stem cells. It appears to have developed over at least the past 15 months, because all 3 of blood cell numbers (but not my Hg) were slightly low at my previous physical in 12/2015, but not low enough for anyone to be concerned.

Since AA is a diagnosis of exclusion, she is checking for a bunch of other things to rule them out. They took 22 vials of blood from me yesterday (22!!!!). I will go back to see her in a few weeks and then she will likely be able to give me a formal diagnosis and we can make some treatment decisions.

The really good news - I do not have severe AA at the moment. Even though my WBC count is low, that is mostly due to low monocytes - my neutrophils are holding their own, and are at a normal level. However, since this has been slowly getting worse for the past 15 months she thinks it's just a matter of time before my ANC starts getting worse as well. So, once we confirm the diagnosis she doesn't just want to watch and wait. But since I "only" have moderate AA right now, and since for the past few weeks I have been stable (low but stable!), we have time to make sure of the diagnosis and discuss my treatment options.

And I am getting a transfusion tomorrow so will get my RBCs and Hg back up for at least a few weeks! I am SO looking forward to not feeling awful for a while.

Thanks for the advice and handholding through this initial process. I'm sure I'll be back with lots of questions, but it has made a huge difference to have a group I can turn to with this initial uncertainty.

[Marlene]

Glad you are in good hands. And you will feel so much better after your transfusion.

Good luck!!!

[kirag1964]

Originally Posted by Marlene

Glad you are in good hands. And you will feel so much better after your transfusion.

I know - I'm so excited!

[bailie]

kirag1964, It is a good feeling to have confidence in your doctor. Let us know when you find out more. We are here to learn.

[Barbara K]

Hi, kirag 1964--I just wanted to wish you luck going forward. I've been following this thread with particular interest because my spouse is now 54, and he was diagnosed about 5 years ago with suspected mild aplastic anemia. He's been on watch and wait (mostly to keep an eye on his ANC count, which hovers between 700 and 900) but is talking with his doctor now about strategies for bolstering his immune system with GCSF treatments because he has been continually sick with respiratory ailments and mild fever for about three months now. That's great you have a specialist now with whom you feel comfortable. We're discovering, too, that it can be important to maintain a consistent relationship with a really good general practitioner who can kind of keep an eye on the bigger health picture, if that makes sense. Best wishes, Barbara.

[kirag1964]

Hello again!

I have another question for all of you. I just got results back from my CBC on Tuesday, and my counts are either the same or worse . My RBC/Hg was pretty much the same (although if they measured today it should be better of course because of the transfusion on Thursday), and my platelets have gone back down to 31 from 45 a week ago. In addition, my reticulocyte count is down to 56 from 75 (last measured about 3 weeks ago).

However, I am mostly concerned about my ANC, which was a bright spot in my previous testing. The first time it was measured on 2/23 it was a 2.5, and it held steady at about 2.0 for the next few weeks. But on Tuesday 3/21 it measured 1.4. While I'm still not in the real "danger" zone, I do not like this trend at all - and for the first time I started to get a bit scared.

I got these results late last night, so I don't know if my doctor has seen them yet. I'm usually super healthy, and right now don't have any signs of illness - is that really what I should be looking for? I am supposed to go to a big fundraising event tonight - is there any reason I should stay home? I do feel that while the transfusion did "cure" my worst anemia symptoms (no more palpitations & I'm not out of breath all the time, yay!), I'm still pretty exhausted and haven't had the energy boost I was expecting. I'm not due for another blood check until 4/4.

Any thoughts would be appreciated!

[Hopeful]

Hi Kirag1964,

It is great that you got in with the AA specialist.

I wouldn't worry about going to the fundraiser tonight. Just be cautious hanging around people if they are obviously ill/contagious. Also (and this may be harder), do not drink alcohol, as it suppresses the marrow!

Sometimes you can have a virus with no outward symptoms that will effect your counts. When your counts are low to begin with, any downward motion can make you sit-up-and-take-notice! Alternatively, if you have AA, your immune attack could be progressing. The good thing about this is that you are likely to get treatment sooner, which can ultimately mean a better outcome.

I never had any outward signs that I was sick until my skin started yellowing because of the transfusions. Most people will never know what you are going through unless you tell them. This can be isolating, or comforting, depending on the situation

With time, you will learn how to tell where your counts are at even without blood tests. For example, I remember that if I felt dizzy after looking at the ceiling and then down again, my HGB was in the 10's.

You will still feel exhausted even after transfusions because your marrow is fighting the big fight right now. The boost in energy level is all relative.

It will be interesting to see what all your previous blood tests reveal.

Hope this helps! Get out there and enjoy life! An ANC of 1.4 isn't that bad...relatively speaking

[kirag1964]

Thank you so much Hopeful! Such helpful perspective and advice!

I'm going to keep just taking care of myself, listening to my body and taking things one day at a time.

[Barbara K]

Just to echo what hopeful wrote as far as relative situations w/ ANC, my spouse's has only measured over .9 or 1 maybe one time over the past several years, and during that time he has worked full time, we've traveled abroad several times and even lived abroad for six months, he's eaten as much raw food as he wants, etc. At issue is not just the ANC count but the marrow's ability to churn out more of them when the situation demands and also how well the ones you do have actually work.

My spouse also has abnormalities with his immunoglobulins (IGG, IGM, IGA, etc.), but even so he has stayed pretty healthy up until this recent bout of illnesses. (He's scheduled for a chest x-ray this week.) He definitely needs more sleep than he used to before all this started, including an afternoon nap, and I think the fact that he has been willing to get that extra sleep (and eat well and exercise regularly but not excessively) has helped.

Btw, you were asking earlier about retic counts. Because my spouse's red cell counts have generally been relatively quite good (around 3.2 at diagnosis I think it was, and now around 3.7 after extensive iron supplementation) we don't focus on them, but I just looked back at his records and see that his retic counts are consistently between 25 and 35 on a scale of 12 to 130, for what that's worth.

I can see why at present you would feel some stress at what appears to be a trend of decreasing ANC counts, but that particular number can be influenced by factors such as time of day the lab work is done (we find that my husband's counts come back lower if he does blood work early in the morning as opposed to right after lunch), whether he has just exercised, and so on, just as hopeful suggests.

Take care.

[kirag1964]

Well, as of this afternoon I have been officially diagnosed with Aplastic Anemia. Since I was watching all the labs come back, this is not a surprise at all - and in fact it's a bit of a relief to have the diagnosis!

I do not have SAA at this time, although Dr. Babushok said I'm pretty close to that (right on the borderline is how she described it). In particular my platelets are trending downward fairly quickly at this time: today's count was 24 down from 31 just a few weeks ago. I had a RBC transfusion 3 weeks ago, and my Hg is now at 8.7 (it was 7.5 before the transfusion, and 9.5 about 10 days ago). I will do a transfusion again once my Hg goes under 8, which will most likely be the case when I get a blood check again in 2 weeks. But thankfully my WBC and neutrophils continue to hang in there - my last ANC was 1.5.

So we are going to move forward with ATG/cyclosporine treatment since it looks like I will probably end up with SAA sooner or later - and it's better not to wait until things get too bad! But since my neutrophils are hanging in there, we can afford to wait until after my daughter's HS graduation in early June, which was the one thing I absolutely cannot miss! So unless something changes drastically between now and then, I will be starting treatment either the week of 6/12 or 6/19.

I'm sure I will have more questions as we get closer to that date. Thanks again for all your help!

[mezoth]

Kirag,

The group at UPenn seem very knowledgeable around AA, I went to them for my second opinion. I have been being treated at Jefferson since October of 2017 for SAA, and have had two rounds of ATG already (the most recent was 4 weeks ago, still hoping it worked). If you have any questions, feel free to reach out to me - I live in downtown Philadelphia and am more then willing to chat with you about ATG and cyclosporin side effects (none of which are drastic).

My HGB transfusion target is 7, but other people I have talked to in the transfusion center at Jefferson have targets as low as 6 - it depends on when you get symptomatic. I have been having regular platelet and HGB transfusions since last October, so I am very used to this process at this point.

If Penn's ATG treatment is anything like Jeff's, expect to be in for 5 days, plus 3-4 if you have any of the "routine" complications (I picked up an infection when it destroyed my immune system on the second round, which kept me in for 3 more days). Expect a couple of weeks after where you just feel... exhausted, but not terrible. And my advice is to do it sooner rather then later - the more bone marrow you go into the process with, the faster your recovery will be if the treatment works.