Why no blood transfusions for 3 weeks after ATG, but then levels fell sharply again?

[Matthew42]

Hello everyone!

I just have a quick question.

My mother has SAA. She had ATG 13 weeks ago, and is still transfusion dependent.

I'd just like to know why she went 3 weeks without a blood transfusion right after ATG + Prednisone. She's been transfusion-dependent ever since (9 weeks later). What caused that? Because before ATG, she needed blood transfusions every 7-9 days.

Now, the only change we've seen thusfar is a rise in neutrophils (now 700-800 from 400-500). Also, she just went two weeks without a blood transfusion, which is the longest she's gone since that 3 week period elapsed after ATG.

Her neutrophils % and lymphocytes % are also trending in the opposite direction.


What do you all have to say?


I wish you all great happiness and health.

[Marlene]

Hi Matthew,

Blood counts will fluctuate so try not to put too much emphasis on each CBC. SAA is a disease of patience and waiting. John's was never on a steady upward trend. He would have dips and then two week later a jump. But overall the trend was upward. It drives you crazy though watching it all play out.

I would put more weight on the absolute count of the white cells instead of percentages alone to try and make sense of things. We were told that you want to see the neutrophil % higher than the Lymph %. But we mostly tracked the absolute numbers.

Regarding red cells...Look at the Reticulocyte, both absolute and %. This can give you a indication if she's making new red cells. In the past, there have been discussions on the age of the transfused cells and the thinking being that red cell that are expiring soon, don't last as long. Whether or not that plays a role in this is unclear. If she's getting two units per transfusion, of course that would last longer than if she just got one.

Also, any infection/fever can drive counts down but that doesn't mean the treatment did not work. They usually bounce back. It may take a while though.

Hopefully others who have had AGT will chime in since our experience was with HiCY. It may be a bit different.

Hope this helps.

[Matthew42]

Thank you for reply, Marlene. So nice of you.

My mother had a very stressful day yesterday, and her platelets are are 16 today after just getting platelets two days ago. That's never happened before. I read that severe stress can cause lower platelet levels. Hemoglobin levels are much more important than platelet levels, but it was another disappointment. Ever since the doctor said that the treatment may not be working, she has been an emotional wreck. I am sure this is affecting her levels somehow, too.

We're at 13.5 week after ATG and things stand: hemoglobin: 7.9 ; platelets: 16 and neutrophils: 600

Neutrophils have been between 600-800 for 5 weeks.

She's going to try to do some very low-intensity exercises. They say it can increase hemoglobin a bit.

Best wishes to you and your husband.

[Marlene]

Matthew,

I'm sorry she's having such a difficult time. It's not easy dealing with this disease. I know she's glad to have you advocate for her though.

Platelet transfusions don't always boost counts. And many/most times don't last but a day or two. Normally, platelets live for only 10 days. There were many times John did not get a bump from his platelet transfusion. His most effective transfusion were at Hopkins when he was in the hospital because they were matching them specifically to him. They could get him to 50K but by the next day they'd be down dramatically.

If you think she normally holds at 16K on her own and she's not having any bleeding issues, you may want to discuss holding off on platelet transfusions and establish a new platelet transfusion threshold. I think 10-20K is pretty standard. John was able to hold at 8K without bleeding issues. He could go lower but we didn't want to set a transfusion threshold lower than 8K, just in case. You can also have them check her clotting times to see how quickly her blood clots.


Take care

[Matthew42]

We're at a little over 14 weeks post-ATG.

Her neutrophils were between 600-800 for the past 8 weeks. Now they're back in the 300-500 level. I really don't understand what's going on. Her WBC count was around 2.5 for two months or so and now it's 0.9??? Could it be stress? She doesn't have a fever. Her lymphocyte count is coming closer into normal range, but not the neutrophils, of course.

Her blood will hold up for about 7-11 days and then it will suddenly drop. She almost went 1 month with only 2 RBC transfusions, but today will make 3. Two more days and she would have only had just 2. That is an improvement from 4-6/month that she needed before ATG.

She had a bone marrow biopsy today, and the doctor said her marrow looked very healthy with the naked eye (the way the blood flowed out). But I don't know what that could mean without further inspection to see cellularity amounts. Just like I am not sure what that means in terms of the autoimmune attack on her bone marrow. But something about aspiration was really good??

Who knows? It is a still a waiting game. She cannot have Rabbit-ATG until early October. You have to wait 6 months. She has another 10 weeks or so before that time comes. Keeping our fingers crossed for a rise in hemoglobin, so she can get off RBC transfusions, which is the most important thing.

I sure hope my mother was diagnosed correctly. I hope she doesn't have something like Pure Red Cell Aplasia, masking as Aplastic Anemia. I never heard of anyone being misdiagnosed with aplastic anemia, but I'm sure it happens. I just always found it weird that her hemoglobin shot up to above 9.5 when she was on steroids after ATG.

Happiness and health to everyone!

[Matthew42]

Things are getting worse. She's needing blood again in less than a week. This hasn't happened since pre-ATG. I am not sure what is going on. She seemed like she was getting a big better by going almost 2 weeks without blood a few time, and now everything is going down except platelets (holding a bit better).

They thought she may have had an infection last week and took a lot of blood for blood culture. I am not sure if that contributed to her lower hemoglobin or not. Who knows really?

My dad said that my mother had a lot of blood taken + blood loss from bone marrow biopsy. This may have contributed to drop of a point or so in hemoglobin. Hard to say again, but very possible.

I suppose we can't give up completely on the h-ATG in just 15 weeks. Maybe her body is in the process of changing or something...I really don't know. The rest of her blood work appears just fine. It's just bizarre: just low platelets, low hemoglobin and low neutrophils.


I wish you all peace and good health.

[Matthew42]

I have a bit of an update:

We didn't know this, but my mother's hematologist consults with Dr. Neal Young at John Hopkin's concerning my mother's aplastic anemia.

Dr. Young confirmed that my mother is indeed responding to IST therapy, even though she is still transfusion-dependent at 15 weeks post horse-ATG. The hematologists have decided that they want to give her another 6-8 weeks before doing a rabbit-ATG. There's still a real chance she could have a full response to horse in the coming weeks, they said. They also saw a little improvement in bone marrow cellularity, along with the fact that her neutrophils almost reached 1000 at a few weeks ago. They also highlighted the fact that slower drops in hemoglobin between transfusions are also a sign that there is some improvement. She definitely has autoimmune aplastic anemia (I never knew that aplastic anemia can be less autoimmune). And the slow response to horse-ATG is most likely to due to only having 5% cellularity in bone marrow, as well as the fact that she is much older than the average aplastic anemic.

Everything looks pretty good so far, but they said she may still need the rabbit "to bring her over the hump"; and her hematologist and Dr. Young say it is not at all risky for her to have rabbit in the coming months, if it comes to that. Why? Because she did well with the horse-ATG administration. The rabbit is just a bit stronger. They would give her longer than 6-8 weeks to see if she has a full response to horse-ATG, but Dr. Young is concerned about staying on blood transfusions at her age. Even though she is otherwise healthy, it's harder on older people. The older you are, the more likely you are to get complications from blood transfusions, especially the iron overload.This is why the hematologist was adamant at the last appointment on doing rabbit in the coming months. It's all because of her age.

By the way, the reason my mother had no transfusions for 3 weeks after ATG was because of the prednisone she was taking. This also proves that her aplastic anemia is very autoimmune in nature somehow.

Only got bad news on one front: She now does have iron overload from getting so many RBC transfusions. It's over 3000! But they've seen many patients with way higher than that. She has a bronze color and little appetite, so that's the reason. But they are going to wait a month or so see if it comes down before doing Exjade. They also want to do a liver MRI to make sure there is no liver damage because she had a liver issue a few months ago (drug-induced liver injury). Her liver panel has been real good so far. So we're going to do wheatgrass, turmeric and quercetin. It's better to try the natural route. Her doctor is not against supplements. It's not necessary to bring it down to under 300 -- just under 1000 or so. A lot of healthy people have iron amounts that are close to 1000, even though it's out the normal range.


Health and happiness to everyone!

[Matthew42]

My mother's absolute reticulocyte count is > 30,000. But it may take a while yet for her hemoglobin to start rising as a result. The way I understand, levels won't match bone marrow function at first, according to the hematologist. It takes a while, especially with aplastic anemia. She said it's like filling up a gas tank a drip a day.

IST seems to be working. We're not getting too excited yet. With this disease, you never know from day to day.


Health and happiness to everyone!

[Matthew42]

Well, I have some bad news to report: my mother fell and had internal bleeding in her brain from severely low platelets. She is expected to make a good recovery from all the signs she has showed since the fall (last Friday).

Interestingly, her hemoglobin rose to 7.9 from 7.5 one day with no transfusions, and her neutrophils went up to 1100/1300 from 500 for few days after the fall. Now, they've all fallen back to where they were before the fall. We're not sure if the horse-ATG is starting to kick in, or it was the hemorrhagic bleed. The doctors say it was not due to the bleed, or shock to the body. They said bone marrow wouldn't start working all of sudden from a brain bleed.

Did the ATG start to kick in at 19 weeks post ATG? She did have increased cellularity in her bone marrow since last biopsy a weeks ago.

How long can you be transfusion-dependent before horse-ATG kicks in? I read that some people on here were dependent on blood transfusions for 6 months or more before the ATG started to work.

We're hoping for the best, but, after this fall, we realize the dangers of the disease (low platelets, etc.). We can't give up hope yet. The bleed is not the issue, no matter how serious it was. She can recover very well, the doctors said, because she has no organ issues and otherwise healthy. But if she cannot get the aplastic anemia under control, her long-term outcome is not good. We know this in our hearts.

Rabbit-ATG is next in a few months, if the horse-ATG doesn't kick in. We're running out of options.

I found out my mother has a small PNH clone in her last biopsy. They said that is a good sign that ATG will eventually work. It means her condition is highly autoimmune, I believe.

Health and happiness to all.

[Neil Cuadra]

Matthew,

I'm sorry to hear of your mother's fall. I hope her recovery goes well.

If her higher HGB was from a single blood test, it may represent only the test-to-test variations that are common. You can only tell a trend from a series of blood tests.

But it's true that ATG can kick in months after the treatment. The signs of successful ATG treatment usually start after about 3 months, but it sometimes takes longer, which is why doctors may wait 6 months to decide if it worked. And when ATG is successful it can take up to 9 months to reach its full effects.

Good luck.

[Hopeful]

Hi Matthew42,

A small (sub-clinical) PNH clone is a favorable predictor for response to IST. There have been a few recent papers and presentations confirming this.

It sounds like mom is in good hands.

Keep the faith!

[Matthew42]

Thank you both so much!

For the past 4 months, her hemoglobin and red blood cells only decline after RBC transfusions. This is no longer the case. Her hemoglobin still drops but then it goes up without transfusions; for example, she got down to 7.3 and almost needed a transfusion. Two days later, she was 7.7 with an increase in red blood cells. This happened 3 times in the past two weeks. This is a new trend. Never before has this happened.

By the way, she's recovering from the bleed, but it will take some time. She also has an infection called discitis in her neck. While the infection won't spread, she has to be on a strong antibiotic because it can destroy her neck bone. Where did the infection come from? The doctors say: just being so neutropenic from aplastic anemia. The doctors are optimistic about her infection, though, or seem to be.

Well, her platelets are not any better. But her neutrophils shot up to 1100-1300 for a few days. Now, they're down to 700, which is all really good. Her neutrophils are almost always below 600 for the past 4 months. I remember the hematologist saying that neutrophils coming up over a 1000 is a good sign that ATG is working, too. Who knows? Hopefully, I am not wishful thinking.

That is all to report.

Note:

Boy, aplastic anemia has caused: an infection and a brain bleed. Wow!

[Matthew42]

Just an update:

My mother is doing better. She is in rehab for brain bleed caused by low platelets a few weeks ago (she fell and hit her head).

They have her discitis infection under control caused by a bone marrow biopsy. The antibiotic may be lowering her hemoglobin and platelets, but it will only be for a few weeks. She has had to get a few more transfusions because of it.

Everything else is fine.

Her neutrophils are now averaging 1000-1500 (past 6 days), which is way better than before, where she was averaging 500. She has never been anywhere near 1000 since she was diagnosed. Her lymphocytes have come way down, too.

We asked her hematologist about her neutrophils staying up so high, and she said that was a good sign. She's 5 months post-ATG. She said that sometimes ATG doesn't kick in until after 6 months in some people (very slow responders). There have been people where it's taken almost 9 months or more to get off RBC and platelets transfusions after horse ATG. That's hard to believe, but that is what they say.

She has a small PNH clone, which is one of the greatest indicators that she will respond to IST therapy. We are keeping our fingers crossed. You never know with this disease.

I wish you all good health and happiness.

[Matthew42]

My mother has been on two powerful antibiotics (drip) for 5 weeks for discitis (most likely acquired from bone marrow biopsy). She has one more week to go. The antibiotics really lowered her blood counts (platelets and red blood cells). The hematologist told her that she wouldn't know if she had any improvement from horse-ATG because the antibiotics can affect your blood counts too much. These antibiotics can even cause temporary dysplasia (production of abnormal neutrophils, etc.). So, because of the antibiotic, they are giving her two units of blood every two weeks.

What's bizarre is that she has modest rises in hemoglobin during the two weeks and then falls drastically over night, which has never happened to her before. Before September, she only had a steady decline after getting a blood transfusion. I wondering if the ATG could be working but is being repressed from the antibiotics. I guess we will find out after next week.

I wish everyone health and happiness.

[Matthew42]

We are being cautiously optimistic as my mother's hemoglobin jumped to 10.5 from 8.6 in a week without any RBC transfusions. This has never happened before since ATG 6 months ago.

Platelets are still low (usually between 11-16), and her neutrophils are not too bad, holding steady between 800-1100.

We are keeping our fingers crossed that the horse-ATG may finally be kicking in. Her hematologist told us a long time ago that rises in hemoglobin without RBC transfusions is the biggest sign that aplastic anemia is going away. Platelets usually (not always) rise last, weeks or months later. She is now only moderately or mildly neutropenic.

Good health and happiness to everyone.

[Hopeful]

That is really great news, Matthew! Infections will also eat through your platelets and RBC's. So, hopefully your mom will see an increasing trend in her counts when she is fully recovered from the discitis.

[Matthew42]

Originally Posted by Hopeful

That is really great news, Matthew! Infections will also eat through your platelets and RBC's. So, hopefully your mom will see an increasing trend in her counts when she is fully recovered from the discitis.

Thank you so much for responding. That is so kind of you!

The hemoglobin can still go up and down for a while (be fickle), but we're hoping she won't need any more RBC transfusions. She is still dependent on platelet transfusions, but we were told that they are sometimes the last thing to come up. It could take several weeks or more to see improvements with them. Her neutrophils range anywhere from 500-1100 (average about 900).

I sincerely wish you health and happiness, Hopeful.

[Matthew42]

We saw the hematologist yesterday. She didn't guarantee the horse was a total success but said my mother is headed in the right direction, and that she was hopeful. My mother would be a very slow responder. She lowered her cyclosporine amount, too, which is a good sign. It is possible for her to still have dips in her hemoglobin in the next few months or so until her blood stabilizes. So, more RBC transfusions are expected for the next 6-12 weeks or so. It's also important to note how long you go without transfusions. So far, my mother has gone over three weeks since her last one. The longest she ever went prior to this was 13 days last July.

We were also told that platelets are usually the last thing to rise.

Health and happiness to everyone.

[Matthew42]

My mother's platelets are almost 50 after 3 days after a transfusion. This is unprecedented for her. She is always between 10-20. We can now say that the platelets seem to be rising.

Her blood did drop a lot since two weeks ago, but the hematologist decided not to transfuse until she goes under 7. She saw that it rose from 8.6 to 10.5 the other week. That was a big jump.

My mother will have gone almost an entire month without a RBC transfusion if she holds out to Friday.

If the horse-atg is a success, my mother is indeed a very slow responder. It's almost 7 months out since atg.

We are cautiously optimistic. You never knew where aplastic anemia will take you.

Health and happiness to everyone.

[Neil Cuadra]

Seven months is indeed on the long end of the scale, but I've often heard that it can take "three to six" months, so seeing results in the 7th month isn't unheard of.

Every hematologist has their own opinion about how low to let a patient's hemoglobin get before ordering the next transfusion. There's a bit of an art to it, I guess. It probably also depends on the patient's circumstances. Anyone who needs regular transfusions over time has to balance the schedule so they get what they need to minimize short-term risks but don't have transfusions more often than necessary to minimize long-term risks.

Congratulations on the improved results!

[Matthew42]

Originally Posted by Neil Cuadra

Seven months is indeed on the long end of the scale, but I've often heard that it can take "three to six" months, so seeing results in the 7th month isn't unheard of.

Every hematologist has their own opinion about how low to let a patient's hemoglobin get before ordering the next transfusion. There's a bit of an art to it, I guess. It probably also depends on the patient's circumstances. Anyone who needs regular transfusions over time has to balance the schedule so they get what they need to minimize short-term risks but don't have transfusions more often than necessary to minimize long-term risks.

Congratulations on the improved results!

Thank you for your kind response.

My mother's hematologist told her that her age is a factor in her slower response. It can take 9+ months for a response, particularly with older people with aplastic anemia (she never told us that at the beginning). With younger people, she doesn't wait as long (that's her opinion, of course). But there is nothing bad about a slower response, other than the wait.

My mother does have iron overload, but she isn't that concerned now as it hasn't festered in the body for that long. But it will need to be addressed in the future if her iron doesn't come down because high iron over years can cause heart and liver damage.

The hematologist is also concerned about antibodies from blood transfusions which can cause her to have reactions to future blood and platelets transfusions. But she said that have to be pretty high to cause real issues. I believe she said that give you medicines to counteract the antibodies if you develop a problem. I am not sure.

Health, healing and happiness to everyone.

[Hopeful]

Wow - Platelets at 50 is a very good sign! Wishing her a long and durable recovery. She is on a good trajectory!

[Matthew42]

Thank you so much. I really appreciate your comments and feedback.

My mother's blood dropped a lot over the weekend, and so did her platelets. Transfusions are still very likely for a while. But that big jump from 8.6 to 10.5 in a week in hemoglobin without a transfusion (not needing blood for over three weeks) was a great thing. Also, she had platelets that were almost 50 three days after a platelet transfusion.

We're just hoping that we will see more increases soon. But the hematologist said that big jump was impressive, and we must be patient. She wasn't on any medications that would have caused such a big increase in hemoglobin without a transfusion.

Her neutrophils are almost 1000 now.

A bit disappointed...but we must be grateful for that one big jump in hemoglobin.

We also found out that my mother may not get stable in blood or platelets until 9 months or more. This is to be expected as she is such a slow responder.

[Neil Cuadra]

Originally Posted by Matthew42

My mother does have iron overload, but she isn't that concerned now as it hasn't festered in the body for that long. But it will need to be addressed in the future if her iron doesn't come down because high iron over years can cause heart and liver damage.

The hematologist is also concerned about antibodies from blood transfusions which can cause her to have reactions to future blood and platelets transfusions. But she said that have to be pretty high to cause real issues. I believe she said that give you medicines to counteract the antibodies if you develop a problem. I am not sure.

Matthew,

There are a few approaches doctors can use to deal with patients who become refractory to transfusions, meaning that the transfusions aren't as effective, don't last as long, or "don't take" at all. For example, it could mean doing additional testing of blood or platelets, or limiting the number of donors.

Even if your mother doesn't (yet) need treatment for iron overload, I hope her iron level is being tested regularly, so you'll know if it becomes too high. This is another area where different doctors have different opinions about when to start treatment, but monitoring is the key.

[Matthew42]

Originally Posted by Neil Cuadra

Matthew,

There are a few approaches doctors can use to deal with patients who become refractory to transfusions, meaning that the transfusions aren't as effective, don't last as long, or "don't take" at all. For example, it could mean doing additional testing of blood or platelets, or limiting the number of donors.

Even if your mother doesn't (yet) need treatment for iron overload, I hope her iron level is being tested regularly, so you'll know if it becomes too high. This is another area where different doctors have different opinions about when to start treatment, but monitoring is the key.

Thank you so much for your response.

My mother doesn't have antibodies yet (she's only had transfusions for 6-7 months), but the hematologist mentioned them. She said some never get antibodies even after years of transfusions, while others may get them in less than a year. Also, a lot of people develop weak antibodies and continue to have them, which are not problematic. She said it's when they get high that you run into issues. That said, there are usually ways to effectively treat high antibodies, as you said above. It's just another concern we have, on top of the iron overload.

As far as the iron overload is concerned, she monitors her liver regularly, as she said that is the organ most impacted by iron overload (monitors enzymes). The heart is, too, but it takes years for iron to build up in the heart and cause real issues in people with healthy hearts. She told us iron overload can also lead to blood sugar issues once in a while, but she will monitor glucose.