Newly Diagnosed

From what I read a large jump in count can be dangerous. But...
Thanks for your replies Carducci!

I do believe in a slow taper - I had no withdrawal, but I did a very slow taper since we lived in Hong Kong and the hematologist wasn't very good and she'd panic if my count decreased & would want my spleen.

Carducci- Now you see from experience what I meant in an earlier post- the doses of Nplate build upon one another. Its a tricky drug and has been endlessly interesting to watch how it works.

I've been on Nplate for 5 years and back when I started there were repeated warnings all over the literature that Nplate was not designed to normalize counts. It was very clear that the target count was 50 and it stated that 80% of thrombotic events happen when counts are over 100. So the general agreement was counts equal to 50, or between 50-100. Dr Drew Provan, an ITP expert in the UK believed counts between 35-50 were the safest. Now it seems that warning has been relaxed on the Amgen website, the warning is there but I don't see it in big letters anymore. I keep my counts around 50 because of that old warning, because I always respected Dr Provan's advice, plus I've known people on this forum who have had strokes and blood clots from Nplate.

Nplate seems to work more slowly for some people than others, along with some people being more responsive to the drug. For example you respond quickly to a dose increase in one week. But it takes me about 2 weeks to respond to a dose increase. A few years back, I crashed to a platelet count of 1. Nplate was increased and next week my counts went up to 15. My hematologist understands that it takes time for the new dose to work to its fullest so he did NOT increase the dose. Following week my count was 65 right where I wanted it to be. I've stayed on that dose now for 2 years. As you are seeing, its something you have to play around with. enjoy the ride!

ps. Withdrawal symptoms from tapering prednisone too fast (adrenal insufficiency) are fluish feeling, body aches, joint pain, muscle fatigue, depression, overall feeling dog-tired and thinking you're coming down with something. If you feel that way it means you're tapering too fast and should probably slow it down. If you are feeling good and have good energy then your adrenals are likely working fine.

Rob 16 posted this a couple of years ago I think, well worth a read
I am cross-posting this article from the National Adrenal Diseases Foundation ( www.nadf.us/adrenal-diseases/secondary-adrenal-insufficiency/ ) because I think it deserves its own thread.
It gives an excellent explanation of how steroids suppress ACTH, causing the adrenal glands to atrophy, and how symptoms of adrenal insufficiency will result as prednisone is tapered below 5 mg.

It is worth reading all of it, but I have excerpted the most relevant parts.

Some interesting points:
If you take steroids for a significant amount of time you WILL develop adrenal insufficiency.
Adrenal Insufficiency can become permanent {I have not been able to confirm this, though!}
Tapering below 5 mg prednisone must be done VERY slowly, depending on how long you have been treated.
The symptoms of this tapering are the result of adrenal insufficiency.
Some degree of adrenal insufficiency is necessary to restart your adrenal glands.
Additional steroids may be necessary in case of illness or trauma.
Every adrenal insufficiency patient should wear an identification bracelet or necklace.
www.nadf.us/adrenal-diseases/secondary-adrenal-insufficiency/
Secondary Adrenal Insufficiency
What Causes Secondary Adrenal Insufficiency
The most common cause of suppression of ACTH is the use of glucocorticoid medications [which] are steroid hormones that act like cortisol. They include cortisone, hydrocortisone, prednisone, prednisolone, dexamethasone {...} When the cells in the pituitary recognize any of these drugs, they sense that there is cortisol present and therefore produce less ACTH. This ACTH suppression {...} can be very temporary, prolonged, or permanent depending on the dose, potency and length of use of the medication. For example, a few days of prednisone will not produce a significant problem, but several weeks of prednisone at a dose of 10 mg will diminish the cortisol level and the ability to fight a stressful situation. Recovery of the pituitary-adrenal response after use of a suppressive dose for more than one month will take about one month. Generally, this one for one recovery time is typical up to about 9 to 12 months, when recovery will often take up to a year or may not occur at all.

What are the Symptoms of Secondary Adrenal Insufficiency
The symptoms are related to the degree of cortisol deficiency, the underlying health of the individual, and the rate of reduction in cortisol level. The most common symptoms are severe fatigue, loss of appetite, weight loss, nausea, vomiting, diarrhea, muscle weakness, irritability, and depression. {...}

If secondary adrenal insufficiency is anticipated, {...} appropriate treatment may prevent any symptoms. However, if it is not expected, there are likely to be progressive chronic symptoms that may be missed or ignored until a sudden event like a flu virus, an accident, or the need for surgery suddenly precipitates a dramatic change for the worse. This is an adrenal crisis and is a medical emergency.

How is Secondary Adrenal Insufficiency Treated
{...}The management of those who have developed secondary adrenal insufficiency from prolonged use of steroid therapy presents a challenge. Once glucocorticoids have been tapered to below 5 mg of prednisone, dosing for stress such as illness or surgery is still needed until there is full recovery of adrenal reserve, typically using a guide of one month for each month that steroids had been used. The most difficult issue is that symptoms of adrenal insufficiency will be present during the tapering phase, because low levels of cortisol are the only trigger to the pituitary to stimulate the return of ACTH production and the restoration of normal pituitary-adrenal responsiveness. The longer high dose steroids were given {...}, the more likely that individual will suffer from adrenal insufficiency symptoms on withdrawal of the steroids. In addition, tapering off the steroids may cause a relapse of the disease that had been treated, causing a combination of disease symptoms overlapping with adrenal insufficiency symptoms. That is why it is very common for steroid tapers to be aborted, with a temporary return to therapeutic doses of glucocorticoids, followed by a slow attempt at tapering if the primary disease is in remission.

Why Should Secondary Adrenal Insufficiency Patients Consult an Endocrinologist
{...} Most cases of permanent secondary adrenal insufficiency should be managed by an endocrinologist. In cases of steroid withdrawal for the treatment of medical conditions, endocrinologists often work with the primary physician or specialist in that disease to assess the recovery of pituitary-adrenal reserve and provide guidance about whether long term glucocorticoid therapy is needed. because I think it deserves its own thread.
It gives an excellent explanation of how steroids suppress ACTH, causing the adrenal glands to atrophy, and how symptoms of adrenal insufficiency will result as prednisone is tapered below 5 mg.

The increase in my count from 38000 to 211000 was both euphoric and scary. I thought they mixed up the samples.
I questioned whether the dose should be reduced but the Hematologist is following the published N Plate protocols to the letter i.e. over 200000 for two weeks then reduce the dose by 1 mcg. I would love to believe my count will be above 200000 again this week so they can reduce the dose but this has been such a roller coaster ride I am not confidant. If something crazy happens and my count jumps above 400000 because they should have reduced the dose with the large jump then per protocol they will not give me a shot this Friday.
From what I can see in various research, the thrombotic events reported have been in the 2% range and those people had some history of cardiovascular issues prior to treatment. That said I will be mindful that the N Plate effect does seem to build up. I do not want to deal with any new issues.
As you said in an earlier post 3 mcg out of a maximum of 10 mcg is not a high dose so if my count drops to somewhere between 50000 and 200000 and I can maintain it there I will be happy.
While i was on the high doses of Prednisone, 70/60/50 mg I suffered with the typical symptoms like insomnia, swelling in my feet, blurred vision on occasion, and increased blood pressure ( I have hypertension). Once I reduced the dosage below 40mg my sleep improved and now that I am below 10mg all of the other side effects have disappeared except swelling of my feet as the day goes on. Other wise I am feeling fine and back to most of my normal activities.
Thank you again for all of the information. It has been invaluable.

I plan to watch this Friday's number closely. If I have another major jump then I will talk to the hematologist about reducing the dose. I do not want a thrombotic event.

Thank you

Thank you for the post. i am at 5mg now and plan to slow down the taper from this point forward even though my Hematologist and Primary Care Doctors show no concern. I have had no withdrawal symptoms but would rather play it safe. I plan to extend the taper by going to 5mg one day and 2.5 mg the next for a week and then to 2.5 mg for a week before going to 2.5mg every other day for at least a week. I will monitor myself for any sign of symptons and adjust accordingly.

Protocol with romiplostim is different in US and UK so it gets confusing. When I was using it I was mindful that it can cause blood clots so I used the lowest dose possible. But the idea with it wherever you are is to keep to a count of 50 or so. We have seen people here on the forum have clotting events with no history of the same and I was mindful of that when using it. I was on it for three years when my count went high and I was able to stop it. I used it very briefly again last year but only needed about 8 weeks before stopping again.

I should add that here in the UK we inject ourselves at home so have more control over dosage.

One thing to know is that it takes at least 4 days for an injection to do anything so you won't get a fast response.

I hope someone can provide input regarding my situation.
Per my earlier posts, my counts first dropped below 50,000 in May 2019. Steroids had no effect on my counts even 70 mg of Prednisone for three weeks.. IVig infusions made my counts jump significantly but after at most a week my counts dropped back. I received four Rituximub infusions 5/22 to 6/14. I started N Plate injections 6/20. N Plate dosage and platelet counts were as follows. FYI, I tapered off the Prednisone and will be completely off within the next few days.
o 1 mcg/kg on 6/20 and 6/27 with platelets above 100000 due to IVig infusions received in the weeks prior
o 2 mcg/kg on 7/5 with platelets at 30000. Clearly IVig effect was gone.
o 3mcg/kg on 7/12 with platelets at 36000
o 3mcg/kg on 7/19 with platelets at 211000
o 2mcg/kg on 7/26 with platelets at 256000. Dosage reduced due to count above 200000 for two weeks at 3mcg/kg.
o 2mcg/kg on 8/2 with platelets at 240000
o 1mcg/kg on 8/9 with platelets at 248000. Dosage again reduced due to count above 200000 for two weeks at 2mcg/kg.
o 1mcg/kg on 8/16 with platelets at 173000
I had a CBC done yesterday 8/19 and my count dropped to 140000.
I am of course happy with my counts over the last 5 weeks. I want to believe that the high counts were due to the N Plate and that the recent drop was due to the reduced dosage at 1 mcg/kg.
My concern is that it was not the N Plate but the effect of the Rituximub kicking in 8 weeks after my first infusion and that the Rituximub is already wearing off causing the drop in the count.
Has anyone had experience that could shed light on my situation?
Any input would be welcome.
Thank you

Thank you for your response.
Do you know how long an injection lasts? I have read that N Plate has a half life of approximately 3 & 1/2 days. In other words a dose at 2mcg/kg reduces to 1mcg in 3 & 1/2 days then 1/2 mcg/kg by 7 days and so on. I assume this takes place after the initial 4 days waiting for the injection to start working?
I just posted recent history on my situation. If you have the time i would appreciate your comments. My counts had jumped to 211000 to 256000 for four straight weeks so my N Plate dose was reduced from 3 mcg/kg for three weeks to 2mcg/kg for 2 weeks and then 1 mcg/kg the last 2 weeks. My count dropped to 173000 after 1 week at 1mcg/kg and 140000 after 10 days. Still great numbers. Eight weeks before my count jumped to 211000 I received my first of 4 Rituximub infusions. My concern is that my counts went up because of the Rituximub not the N Plate and that it is already wearing off after only 1 month causing the drop.
Any thoughts?
Thank you in advance.

I don't think its Rituxin. Just my opinion- I think your counts are acting like Nplate. Rituxin doesn't "wear off" like that generally. It knocks out your Bcells for about 6 mos, so if you have a response it usually lasts 6 mos or longer. Its possible that its both Rituxin and Nplate, just have to watch how it goes. If you can taper off of Nplate and your counts are still over 100 then you'll know its Rituxin.

There are no absolute rules on how Nplate works. Everyone seems to respond differently. So if you want to understand what your counts are doing, I wouldn't think in terms of half-life and that, honestly. Just look at the pattern of numbers, and from there you can figure out how your body is responding to Nplate. And also as I've said before, the doses build upon one another. That is evident in the pattern of your platelet counts.

My hematologist says with Nplate "you have to give it time to work". Thats important, because the Nplate doses are building upon one another, you have to give each dose time to reach its full potential.

So 7/5 when you increased the dose to 2mcg your count was steady at 30. I would have stayed at 2mcg to "give it time to work". If you had stayed on 2mcg then I believe your counts would have slowly climbed (which is preferable to shooting up). The raise to 3mcg hadn't kicked in yet on 7/12, but by7/19 all of those dose increases have built up and your counts shot up over 200.

On 8/9 with counts of 248 your body is still responding to 3mcg of Nplate. I think it hadn't worn off yet. Then the next week 8/16 your counts reflect the 2mcg dose decrease. It appears that the effects of Nplate are lasting about 4 weeks. My advice would be stay on 1mcg or whatever dose you decide on for 4 weeks to get some stability. Unless of course your counts are too high which could mean the Rituxin is working.

Hope this makes some sense. Nplate is a tricky drug for sure! I've been on it 5 years so I know how it works for me, but everyone responds differently it seems. Great that you are on such a low dose- good luck

I can't thank you enough for this response and your past responses. The insights from your experience are very valuable.
I did see at least one study with people who received four Rituxin infusions and initial response varied from 1 to 15 weeks after the first infusion and duration of response varied from 12 to 42 weeks. My numbers jumped 8 weeks after my first infusion i.e. 7/19 but then my count dropped 4 weeks later so i agree it does not seem to fit the normal Riruxin pattern.
My Hematologist is strictly following the N Plate published guidelines i.e. increase 1mcg/kg if below 50,000, reduce 1mcg/kg if above 200,000 for two weeks in a row, and stop injections if above 400,000. I have not had enough experience at this point to give him input on the dosage but I will start to focus more on the pattern of my numbers as you suggest and see where it takes me.
If I continue to drop at the same rate as I have the last 10 days ( 240000 to 140000 in 10 days or 10000/day), my count will be around 100,000 by this Friday when my next blood test and N Plate injection are scheduled. Based on past practice my Hematologist will keep me at 1mcg/kg for the third week in a row. My concern is that at 10,000 per day I could be down to 30000 by Friday 8/30. Do you think that will be the case or do you think the consecutive doses will build and I will plateau closer to 100000? If I can stabilize near 100000 with a 1mcg/kg dose I would be ecstatic.
Any further input you could provide would be greatly appreciated.
Thank you

I did Romiplostim (NPlate ) for a year. 1mcg/kg did nothing, 2mcg/kg sent count from 24 to 76 in a week then counts stayed around an average of about 60 for 2 months then dropped to 21. Haemo said I would like you to stay on this dose a bit longer to see if that was a blip but weekly counts please:- 93, 42, 230, 44, 45, 33, 28...up to 3mcg/kg:- 118,110, then swung about all over the place from low 30s to mid 100s. The day before a planned op count was 6 and op was cancelled. End of my foray into the world of injectable TPO.

Carducci- Mrsb's example was the best answer to your question- what will happen next? Nplate is too illogical to imagine that your counts will continue to fall in a pattern of 10,000 per day- that would be too predictable for Nplate. Plus there are so many variables that are unknown. But that said, I think you could achieve stability on Nplate if you can stay on one dose long enough. Right now your dose has been changed every week to 2 weeks. So it will be very interesting to see what happens with your next count. As you said, that will tell you if you can stay on 1mcg.

If your counts fall below 30, your doctor will raise the dose back up to 2mcg. If that happens then I would stay on 2mcg for at least 4-8 weeks just to let your immune system settle down. Yes, as you said, your doctor is following Amgen's protocol and thats good. Its just that over the 12 years that Nplate has been out, my doctor and others have figured out how to achieve stability with the drug and the key is to stay on the same dose long enough to see what that dose is going to do. AND as Mrsb's story illustrates- not everyone can achieve stability on Nplate. Several people have really tried with that drug, have only had wild swings and never could get a consistent platelet count on Nplate. Keep us posted!

If you dropped out of the injectable world, what treatment are you utilizing?

Thanks for responding.

Wow, you're at dose '1' already. Doing very good Carducci.
Cheers to remission via Nplate!

Thanks.
Waiting to see count this Friday after two weeks at level 1. Expecting a significant drop from weeks at 3 and 2mcg. Assuming I continue at 1mcg, I may drop below 50000 and have to go back up to level 2. My best guess at this point based on my count at various dose levels is that 2mcg will be where I will end up to maintain a count above 50000.

How are you doing?

Carducci I am on Eltrombopag (Promacta) and have been for over 2 years. Generally I have much more stability of counts. There is the odd drop (viral or stress related) but a quick Pred boost sorts that out.

Carducci- Just for fun I would guess that your counts will be over 50 on Friday. It's because your counts are dropping so gradually. Your dose was lowered pretty dramatically from 3mcg to 2mcg to 1mcg in just a couple weeks and yet your counts are sort of drifting down. Many people would crash with that dose reduction. I'm just thinking if you were going to crash it would have happened already. Also when your numbers were over 200, the counts were very stable- that is a good thing! You are having a great response to Nplate overall.

Thank you as always. Your messages always seem to come when I am feeling stressed out and worried.
As I mentioned my count last Friday was 173000 versus 248,000 the previous week after weeks with my N Plate dose at 2mcg/2mcg/1mcg. I had a blood test as part of a physical at my Primary Care Dr on Monday and the count dropped to 140,000 so 33,000 in 3+ days and 100,000 in 10+ days. To me that is crashing but I don't have the experience to make that call. Based on your previous message if I am above 100,000 I am going to question my Hematologist as to the possibility that the Rituximun is effecting my count. If I drop to the 50,000 to 100,000 range I am going to ask if i can receive a 2mcg versus a 1mcg injection. I would rather do that than stay at 1mcg and crash below 30,000 just to get the 2mcg injection to get back up over 50,000. As you said, I would rather get to a stable situation and dose than continue to ride a roller coaster up and down. Problem is the Plate protocol says you raise 1mcg when you are below 50,000 so my doctor may not be willing to raise the dose if I am between 50000 and 100000.
I analyzed all of my previous numbers as you suggested and I agree that unless it is the Rituximun, my count will probably be between 50,000 and 100,000 today. My gut tells me 2mcg is where I need to be to get to a stable situation. We will see what happens and i will let you know if you were correct that the Rituximun is having an effect or you were right that my count will be above 50,000.
I hope you don't mind another question? When my count was at 6,000 back in June I injured my right hand twice hitting it against hard objects the week before I crashed. The bruising was very bad and took weeks to disappear. Since then I have had bruising on that same hand even when my counts were above 200,000. The bruising heals quicker but I seem very susceptible on that hand with no recent bruising anywhere else. i am wondering if my hand has been through to much trauma and is just weak? Your thoughts?
Thank you ahead of time for taking the time to respond. It is greatly appreciated.

Just got back from Hematologist. My count was 105,000 after 08/02 240,000 and 2mcg, 08/09 248,000 and 1mcg and 08/16, 173,000 and 1mcg. Received 1mcg today. Hemo thought about going to 2mcg but concerned about possibility of thrombocytosis.
So you were correct in your prediction that my count would be above 50,000. Not sure if you are correct about your prediction that Rituxin is playing a role in my count. Dropping from 173,000 to 105,000 is significant but staying above 100,000 after 2 weeks at 1mcg? By next Friday the effect of the earlier doses at 2 four and five weeks prior and 3mcg six weeks prior should be minimal so I should get a true reading of where my count will be at 1mcg. If miraculously I am still at or near 100,000 do you think that will indicate the Rituximan is working in the background?
Anyway just wanted to let you know your prediction was correct and again to thank you for your help and guidance.

Great news Carducci, that is a great count! Yes, I still would call this a slow drifting down rather than a crash- haha all depends on your point of view.

Your doctor was wise to not increase your Nplate dose to 2mcg. There would be no point in shooting your counts up to 200 again and it really is risky. These TPO drugs, Nplate/Promacta can cause blood clots and stroke. So I like your doctor! He really knows what hes doing and follows the dosing protocol.

I think what I said about Rituxin was that if you could taper completely off of Nplate and your counts were still staying up around 100 then you'd know that Rituxin was working. I'm tending to think you are responding to Nplate but its hard to say when 2 drugs overlap. Time will tell. Meanwhile you are having an awesome response to one or the other, or both!

I'm sorry I don't know much about the bruises. Some people say that Vit C will strengthen blood vessels. I avoid Omega 3 and turmeric as they are natural blood thinners.

Don't be sorry for not knowing about blood vessels. You have been so knowledgeable about everything I thought I would ask.
I understand what you are saying about the Rituximun. I will be interesting to see if my count drops this week and if so how significant a drop. If I stay above 50,000 then I will go another week at 1mcg. At that point, there should be very minimal effect from earlier higher doses and I assume 1mcg will be my on going dose. As you said earlier if I drop below 50000 I will go back to 2mcg and assuming I then stabilize above 50,000 2mcg will become my on going dose. I want to believe the roller coaster ride is nearing an end or at least the ups and downs are getting flatter as I zero in on stability.
Hopefully I can update you in the next couple or weeks with good news.
Thanks again for everything. You really have helped keep my blood pressure under control.

You were right when you said if your counts drop by 10,000 per day you'd be at 100 by Friday. Your logic was right! I doubted that Nplate could ever be so predictable. Yes as you said, I wouldn't think your counts are being driven by the higher doses now, only the 1mcg. Can't say for sure but seems very possible that you could level off above 50 with this dose. Will be interesting to see what happens next!

You mentioned if you stayed at 100 would Rituxin be working in the background? hmm.. that would be hard to know. It would be possible that Nplate is doing nothing and rituxin is keeping your counts up. Sometimes people will have 3 or 4 drugs going at the same time and no one knows which one is working. I still have to think Nplate is doing its job because your counts are correlating to the Nplate dose changes.

Thank you as always.
I think this week will provide a good indication of whether the Rituximun is working. If I continue to have a significant drop in count then I agree I am following the N Plate dosage. If I stabilize near 100,000 with 1mcg NPlate then I am either very responsive to the NPlate or the Rituximun and NPlate are working together.
I will be happy when I can hopefully reach a stable count based on a stable dosage.
What is your guess for my count this coming Friday?
I will keep you posted.

Carducci7292 wrote: Just got back from Hematologist. My count was 105,000
...
Hemo thought about going to 2mcg but concerned about possibility of thrombocytosis.
...

I like the way that doctor thinks too.

My count guess for Friday is: 105.

What do you think is keeping my count up, Rituximun or NPlate or both?

Thanks

My count was 113,000 today up from 105,000 last Friday after three weeks at 1mcg N Plate.
When I was at 2mcg my count was in the 170-180,000 range and when I was at 3mcg it was 240-250,000. I am starting to think the Rituximun is having some base effect and each mcg of N Plate is adding to the count? I received 1mcg again today and will be meeting with my Hemotologist next Friday in hopes of getting some clarity. Feeling good about my results.
Can I ask how you handle travel when it extends beyond a week? I have a trip planned from Sunday to Saturday with three plus days in each of two locations and I don't think I will be able to arrange to receive an injection on my normal day, Friday. Should I wait until the following Monday for the injection?
Thanks as always for your input and insight.
Regards

pdsa.org/discussion-group/7-treatment-general/30158-travel-other-lifestyle-changes.html#64665

pdsa.org/discussion-group/7-treatment-general/30250-nplate-injection-at-home.html#65579

Carducci- great counts! very good news- I thought Hal's guess of 105 was a bit overly optimistic but he was right! Unfortunate that you have to travel right when your counts are stabilizing but life happens. So.. again the mystery of what is working??
If Rituxin is keeping your counts up then you can miss your injection and theoretically counts should be the same- right? But if Nplate is keeping your counts up then your numbers should drop if you miss your Friday injection. It kind of seems as though your only option is to miss your dose on Friday and get right in on Monday to check your counts and get your Nplate.

If its any comfort I have missed a whole week of Nplate a couple times (injection on day 14). My counts dropped from 40s to 15 and 16. I don't worry about numbers in the teens as I don't have bleeding issues. I have gotten injections on day 9 and day 11, counts didn't drop much on day 9. I think they went from around 40 to 26. Those numbers are fine for me. Its important to watch symptoms and not just the numbers. I also always carry prednisone for emergency. 10mg prednisone will bump my counts up to 50 within 24-48hrs. I try to time vacations so I get an injection the day before I leave and get right in the day I come back, but as I said sometimes its over 7 days. Will be interesting what your hematologist says.

Good count Carducci
If I were you I would be inclined to skip the injection and have a count done on return. This could be the way to find out if it is the Rituxin or not that is holding your counts.
As Poseymint says take some Pred with you in case of emergencies.
Enjoy your trip.