Recently Diagnosed. Advice on Next Steps?

Hello, I am a 31 year old male recently diagnosed with ITP. After going in for a routine physical back in November 2015 my platelets came back at 36. I wasn't actually diagnosed until January 2016 after ruling out all of the other possibilities. Ultrasounds came back normal and bone marrow biopsy suggested ITP as well. I could have been living with ITP for as long as two years which would have been my last blood test prior.

My hematologist was pretty sure this is what we would find from the beginning but it has certainly been a roller coaster of emotion that I know you all are familiar with. You don't know if what you have is going to end up a minor inconvenience or something that is going to kill you in 6 months and everyone seems terrified to speculate or reassure you in any way. The toughest part was the news came about 5 weeks after we found out we are having our first child. I was kind of a wreck there for a minute lol. Good news though that it was the lesser of all the evils and indeed ITP.

Since November my count has ranged anywhere from 20 to 84 and everywhere in between. To this day I have practically no symptoms which is strange to me but doc says it is because what platelets I do have are large and immature.

In regard to treatment, I initially took a 3 or 4 day round of Dexamethasone which made count jump from 53 to 83. 8 days later they were back at 33.

I started Prednisone 60mg on 12/16 and have been on that dosage to date aside from about 4 days where we tried to taper but it tanked again.

With no significant change from Prednisone I started on Rituxan infusions once a week for 8 week plan on 1/20/16. I had my 6th treatment this week and my count was at 33 again when they took my labs prior to hooking me up. I know Rituxan is infamous for delayed response but it is looking like we are probably going to be discussing next steps by week 8.

Through all of the medication I have only had mild side effects. I am tolerating it all very well. A blessing in all of this.

The next treatment phase he is leaning toward is splenectomy given my age and because he is not completely comfortable with the long term track record of some of the other drugs. I told myself if it got to this point I would seek a second opinion so I have an appointment scheduled with Mayo Clinic following my last round of Rituxan as well.

I lead a pretty active lifestyle and I know my doctor wants to get me back to where I was. Prior to my physical I was training martial arts and sparring among other recreational activities that are not very ITP friendly that I love. Obviously I've had to quit that in the interim but it is a blessing we found this when we did.

Our baby girl is due on May 17th so I'm weighing out surgery vs. just living with it for now if deemed safe enough. However, I am not sure of recovery times for splenectomy and if I need to be overly concerned with the timeline etc.

I guess I am posting to see if this sounds familiar to anyone and if there is any good advice out there for where I am at. The thing I'm struggling with the most is not being able to get a good idea of what life could look like from here on out. It seems like it's anywhere from something works and it remisses forever or I could be going through treatments several times a year or be on steroids indefinitely. How often do people just walk away from this with no further issues? I'm prepared for whatever it is but I'd love for someone to just tell me the blunt truth.

I'm hoping to get as much information as possible at this point and any help the community can provide would be great! Thank you very much!

Joel:

Hello. Welcome to the forum.

I've read your story and you might think that what I'm about to say is odd, but I'll say it anyway. I don't think you've really needed any treatment at all. 20k is a safe number, especially if you don't have any symptoms at all. One thing that is usually stressed by the top ITP Specialists is to treat the symptoms, not the numbers. You've had a lot of treatments thrown at you in a short time that may have been unnecessary. Most here would not treat at all with counts in the 30's; I wouldn't. People do not need 'normal' counts, only 'safe' counts.

Since ITP can be chronic, some people are on and off of treatments for many years. The side effects of those treatments take a toll. I'm not talking about short-term side effects, I'm talking about long-term damage that accumulates. Right now you seem to be a very healthy young man with lower than normal platelets. Once you start using these drugs, other problems can begin.

I would suggest a second opinion. The protocol for Rituxan is 4 treatments, not 8. There is research that suggests that even 4 treatments may be too many for ITP; the 4 dose standard was based on the dose used for lymphoma treatments. Studies have shown that patients responded to two treatments as well as they responded to 4, so 8 is definitely overkill. More is not beter. Once the B cells have been targeted, they are gone. More infusions won't do a thing. I consider Rituxan to be a heavy duty, toxic treatment. I've used it myself and did have health consequences from it. It can take 4 to 12 weeks after stopping Rituxan to see a response, so you need to give that more time.

As far as splenectomy, I wouldn't even consider that right now. ITP can resolve sometimes within the first year and if you have the splenectomy, you will never know if that might have happened. The spleen is important, especially for those with autoimmune disorders. Also, it is becoming a treatment of the past, very few doctors suggest it any more. The top ITP docs do not recommend it any more. It doesn't always work, can fail at any time, and there are better options these days.

The biggest problem I see now is that once you have Rituxan, the vaccines necessary prior to splenectomy are not effective for 6 to 12 months after the infusions. I can provide the data for you if you want. Splenectomy after Rituxan is not a good idea, especially since you are symptom free.

Another odd thing that might be hard to understand right now is that people with ITP are susceptible to blood clots. There are several reasons for this, but splenectomy raises that risk and it is life-long. If splenectomy does not work and you end up having to use other treatments, that can raise the risk even more.

I know that your main goal right now is to get platelets up and you are willing to do whatever it takes to do that. But there is so much more to learn about all of this and looking at the big picture is very important. You don't want to trade one problem for others.

I know that you are active and that seems to be the only problem with backing off of treatments. Some people do choose to treat because they don't want to give up their activities. I would like to at least suggest that you slow down a bit here. It isn't a race. Rituxan may very well work for you, there is still time.

Hi Joel,

It is not too late for Rituxan to be effective. Eight to twelve weeks is not unusual, and even longer, for it to take effect.

The treatments for ITP can be more risky than the ITP itself. The drugs Promacta and Nplate are an exception to this, as they appear to have a pretty good safety profile, and sometimes produce a remission. They are very expensive, and insurance is not always willing to cover them, but often will after Rituxan has been tried.

The spleen is not a useless "vestigial" organ. It is an important part of one's immune system, as well as providing an emergency reservoir for one third of one's platelets. Splenectomy does not always work. Being asplenic exposes you to certain infections for the rest of your life. Even if splenectomy were a good idea for you, this would be much too early to consider it, as ITP can resolve on its own in some cases.

A lot of people with ITP that is not too severe will choose not to treat, or to treat only when symptoms appear or counts get too low. My wife is at that stage now, having had a partial remission since Rituxan treatment 18 months ago, with counts mostly in the fifties, occasionally dropping into the twenties. Watchful waiting, as it is called, works especially well if one responds quickly to rescue medications, like prednisone or IVIG.

The martial arts and other sports may be a factor. Bruising is not the issue. The issue would be mostly head and abdominal contact that might cause internal bleeding. If I had to choose between risky sports and keeping my spleen, I would give up the sports.

Congratulations on the child. Hopefully the ITP will become a minor distraction, as it has for many here.

Edit: I see that while I was hunting-and-pecking, Sandi posted the definitive response. She is our resident guru and moderator.

Thank you both for your quick replies!

I would definitely agree on slowing down. I've just been going with the flow and I guess I was just looking for some confirmation from others with experience. It is hard for me to judge what information is good information because there is so much of it out there. Splenectomy is definitely not a route I'd like to go and especially so soon. What you are saying makes sense to me to give it some time to work itself out. I am certainly ready to start tapering off of Prednisone. I suppose I will just continue with these last two treatments and make the request to taper as soon as possible.

Yeah and that Sandi gets bossy sometimes. Ultimately Joel, the decisions are yours. With ITP though, you need to do your research. Kitchen sink approaches are not always the best course of action. We all tend to want to rush and fix this, but with ITP, there are no quick fixes. It can take time and patience. These treatments are not innocuous though. Less is always better and you want to do what will keep you safe, and not necessarily normal. Some doctors are all gung ho with treatments and bring out too many big guns. They get a bit too focused on the problem at hand without thinking ahead. Your future is important too.

You do not have to finish the treatments.

As far as credible information, any articles that you find on this site (and there are many) are credible. They were written by the top ITP doctors. Anything from bloodjournal.org is credible. If you're not sure, ask us.

Here is a good video:

fhs.mcmaster.ca/medicine/hematology/ITP-2010/player.html

I am with sandi on this one, why on earth would they treat you at 53 or even 20? I would definitely just monitor your count

You've been given some great advice by Sandi and Rob, but I just thought I'd jump in with my agreement of what they have said. If you are having few to no side effects, I would completely be fine with staying at counts of 20,000. Treatment can cause so many negative side effects and please don't let them take your spleen so easily! I had mine taken as a treatment for ITP as a child (at age and I'm still dealing with my ITP as an adult (counts anywhere from 20K-60K). I have the additional worry of potential for clotting problems and infection problems because I don't have a spleen.

I think getting a second opinion and finding a hematologist with lots of experience with ITP is a great suggestion. You don't want a hematologist who is just going down a treatment list (and in a big hurry from what it sounds like!) and who is shooting for "normal" count numbers.

Good luck to you and congratulations on expecting your daughter. You will have so much fun with her

Thank you all for your great advice and for taking the time to respond!

You have definitely given me some things to think about. I needed some reassurance that it is not time to consider splenectomy and you have all confirmed that for me. I am going to move forward with the second opinion through Mayo Clinic just to cover all of the bases. I also set aside some more time to speak with my doctor next week prior to continuing treatment to get a better understanding of why we are on the current path.

I think the most concerning thing you had said Sandi was that Rituxan can render the vaccines given prior to splenectomy ineffective for 6-12 months. So let's say worst case scenario I back off of all treatments and all the sudden experience symptoms or an episode that were to lead to emergency surgery I'd be in trouble. I would be interested in seeing that data if it is readily available.

Thank you all again!

Keep your spleen. Is my advice and get off the pred as soon as you can.

Joel:

I have been on this Forum since 1998 and have seen thousands of people come and go. In that time, I have only ever seen one emergency splenectomy. Splenectomy is usually elective, as in 'choice'. It is not 'necessary'. The person I'm referring to had low counts, nothing else worked, and they had serious bleeding. Since that time, two new drugs have been created for ITP that have a very high success rate, which has drastically changed the way ITP is treated. I rarely ever see anyone have uncontrolled bleeding, even with low counts. Elderly people tend to have more problems with bleeding because they have thinner veins and arteries. Young people can generally handle low counts better. You are also one who does not really have symptoms at 20k, and that is also on your side.

Abstract

B-cell depletion may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). We investigated the effects of rituximab on antibody and cellular responses to Streptococcus pneumoniae polysaccharide and Haemophilus influenzae type b (Hib) vaccines in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n = 17) or placebo (n = 7). Among 20 evaluable patients, 3 of 14 (21%) in the rituximab group and 4 of 6 (67%) in the placebo group achieved a fourfold increase in anti-pneumococcal antibodies (P = .12). For anti-Hib antibodies, 4 of 14 (29%) and 5 of 6 (83%), respectively, achieved a fourfold increase (P < .05). Fewer patients in the rituximab group demonstrated Hib killing (2 of 14 [14%], 5 of 6 [83%], P < .05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, preplasma cell blasts and interferon-γ-secreting T cells were reduced in rituximab-treated patients. Antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with depleted B-cell pools. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in ITP patients.

www.ncbi.nlm.nih.gov/pubmed/23851398

During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen.

www.ncbi.nlm.nih.gov/pmc/articles/PMC3659395/

If you received vaccinations within six months of receiving rituximab (Rituxan®), they were probably ineffective. In a new study, people who received pneumonia and flu vaccines six months after their rituximab treatments had a significantly lower response to these vaccines than the placebo group. Nearly 20% did not respond to the vaccines at all. Rituximab depletes B-cells (cells that make antibodies) and also reduces cellular immunity (the part of the immune system that doesn’t include antibodies), both needed for a healthy immune system. This cellular depletion lasts at least six months and has implications for the lack of response to vaccinations and the increased risk of infection seen in rituximab patients.

Nazi I et al. “The effect of rituximab on vaccine responses in patients with immune thrombocytopenia.” Blood. 2013 Jul 12.

www.pdsa.org/products-a-publications/e-news/2013-e-news/item/924-platelet-e-news-august-29-2013.html?tmpl=component&print=1



After treatment with rituximab, immunological responses to both polysaccharide and conjugated vaccines are impaired in patients with ITP.

Splenectomized patients who received rituximab may be at increased risk of infection because of compromised immune responses to vaccines.

www.bloodjournal.org/content/122/11/1946

PS. I cited that video for you to watch. In it, Dr. Drew Provan (top ITP Specialist) says that he has not seen people dropping dead due to not having splenectomy. He deals with very severe cases and several people from the US have traveled all the way to the UK to see him. His word is gold as far as I'm concerned.

Now, about Rituxan.....I know I'm throwing a lot at you. But I believe it's better to be an informed patient so you can advocate for yourself. Many Hematologists are not up to date with ITP as some consider it to be a benign disorder compared to the other illnesses that they treat. Most Hematologists have their specialty illnesses (certain types of cancer), so do not focus on ITP or bother to read updates. Some older doctors are old-school. If you went to five different doctors, you'd probably end up with five different approaches.

Statistics have shown that more people die from infection than they do from bleeding. I can provide articles about that too. This study quoted below suggests that two infusions are enough to treat ITP patients. I can provide more if you'd like.


We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m2 and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician’s preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 109/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.

www.bloodjournal.org/content/124/22/3228

That is good to hear and I welcome any new information at this point so no worries! Thank you for providing the info on Rituxan that makes a lot of sense. You would potentially be putting yourself in a lot of unnecessary danger by moving directly on to a splenectomy after suppressing the immune system for several weeks. I was feeling like a splenectomy was somehow necessary but that was just from ignorance and not asking the right questions. Everyone's experience with ITP seems to be slightly different so I had no idea what to expect.

Ideally, taper off of the pred asap and see if the Rituxan has a delayed response. In the meantime just keep an eye out for symptoms and focus on diet and exercise and maybe it runs it's course. I haven't had a chance to watch the full video you sent just yet but I plan to tonight. I'm looking forward to learning more!

Looks like you get it. Only thing is, don't taper off of Prednisone too fast. You will have withdrawal symptoms and that isn't pretty. What dose are you on now?

Prednisone, Rituxan and splenectomy are all immunosuppressants.

I am currently on 60mg and have been on that dose since 12/16/15. Aside from 4 days in January where we tapered to 30mg but platelets dropped and so we went back up to 60mg. Everything I've read since then suggests a much slower taper so that is what I am going to do.

I didn't have any issues during that 4 days when dose cut in half. I seem to tolerate Prednisone pretty well and I think it is because I had to take it many times for brief periods growing up due to asthma and allergies. I am knocking on wood as I type this (which is difficult) but I'm hoping the withdrawal goes smoothly and no major side effects.

Yeah, I'd go slow with that dose. I'm glad you are not having too many side effects. You're rare. I always found that the more I had to do Prednisone rounds, the worse the side effects got.

What are your counts?

Sandi,

My last count was 33k. That was from Wednesday 2/24.

To give a clear picture when I started the Dexamethasone in the beginning I quit taking all medication other than what I am being prescribed for ITP. I was taking Zyrtec and Flonase once a day for allergies and a multivitamin. I also quit drinking alcohol. I still have a cup of decaf coffee a day which I know has a small amount of caffeine but I have avoided caffeine for many years. I read somewhere that could affect your count but I don't know it seems like just about everything could.

Since November 2015:

36 (initial test from physical)
42 (confirmation test)
53 (prior to starting any medication)
83 (after short round of Dexamethasone)
33 (drop after Dex. Started Prednisone 60mg)
58
64
84
61
42
32 (after 4 day Prednisone taper)
37 (started back on 60mg of Prednisone)
44 (Started Rituxan)
64
20
32
56
33

Joel,

As I read it, steroids seem to have little or no effect on your platelets. Your initial count was 36, but it has been as low as 20 while on prednisone, and is at 33 now, essentially the same as when you started. The ups and downs could easily be random variation. I would try to taper off, and see if platelets remain at a safe level, and whether symptoms appear.

When are you going to Mayo Clinic? I am glad you are getting an expert opinion.

All of those counts are really above treatment level if you are symptom free. Some people treat at 20k because they feel more comfortable, but it's not necessary. The high dose of steroids don't seem to be doing much.

I wouldn't worry about the coffee so much. You're right, it does seem like everything can affect counts so we like to say 'use in moderation'. You can't quit everything. The main thing is to stay away from aspirin, Vitamin E and omega's because those can thin the blood. You don't want that.

I agree I have felt that way for a while. Just that it isn't affecting count either way. That is why we tried to taper about halfway through.

One thing I do think is it is possible the Prednisone may be helping me tolerate the Rituxan a little better. I had a slight reaction on my first dose where I started wheezing and got a bit flush. I was due to take my Pred for the day and right after I took it I was fine the rest of the way. I know it has helped me transition off of my allergy meds as well.

Quite honestly, even knowing what I know now I would have probably agreed to all of the treatment steps taken so far with some changes in duration/dose certainly. When I initially found out I just wanted everything to go back to normal as soon as possible, but I've settled into the idea I am likely going to deal with this in some capacity from here on out. I'm just trying to learn everything I can about managing the disease and avoiding surgery.

Rob, my appt. with Mayo Clinic is in a couple weeks. I'm going to have all my records and slides from my biopsy sent down so that they can double check the diagnosis as well as advise on further treatment/non-treatment.

Sandi, question about the Omegas. Does that mean you avoid eating fish?

No, don't avoid eating fish. You still need that for your general health.

I hope the second opinion is helpful.

Joel, you are getting lots of good advice. I will just throw in my small 2 cents worth.

Had ITP first in 2001, 100mg for two months and a 6 month taper, the good news was a 5 year remission. Had Retuxin four treatments and no prednisone in 2006. No one mentioned splenectomy but the first couple of days hemo did and my GP said no way. Have different Hemo now that I love working with.

Two years ago I had double cataract surgery 15 years before most folk need it. I am 59 for a few more weeks. Most folks are 70 or even 80 for cataracts. Eye doc blamed the prednisone.

So long term changes ARE a factor in treatment decisions . I would not consider splenectomy either.

Best of luck to you and congrats on the baby.

Non-contacts martial arts do exist. I love Tai Chi.

Thank you Cindy! I am sorry to hear about your surgery. I hope that you are doing better these days! That was definitely a long time to be on Prednisone and it wouldn't surprise me if it was the culprit. Hoping everything goes smoothly here when I start tapering and counts stay safe. I certainly want to avoid any long term complications like so many of you have experienced.

Joel wrote: I certainly want to avoid any long term complications like so many of you have experienced.

The key to that is to treat only when necessary, use the least toxic treatment, and use the lowest possible dose. Immunosuppressants raise cancer risks over time, among other things.

I wanted to follow up with everyone who has helped me and let you know the results from my trip to the Mayo Clinic.

The diagnosis of ITP was confirmed in his opinion. The doctor reiterated a lot of what you on this forum had stated. Basically, he would not have treated as long as my platelets were safely above 30k.

However, if I had opted to treat, they would have given me the vaccines that go along with splenectomy prior to administering Rituxan in preparation for possible unsuccessful treatment. The Rituxan alters your immune system and the B-cells for up to 6-9 months after treatment and can make the immunizations less effective.

He recommended continuing to taper off of Prednisone of course and seeing if my counts can stay stable above 30k without it. If so those are perfectly safe numbers to live with after making some slight lifestyle changes.

If it turns out that the Prednisone is what is keeping them stable then his recommendation would be a few months of Nplate to get me to the point of getting immunizations for splenectomy. He feels splenectomy is the best long term solution for someone my age, but only if you are experiencing symptoms (which I am not currently).

He also stated that the Rituxan could still work up to 3 months later and not to do anything unless necessary within that timeframe.

My platelets are trending up at 79k and I am tapered to 10mg of Prednisone (down from 60mg) so I am feeling pretty good about that. Maybe we will ultimately see a big response from Rituxan. I'm prepared either way!

To those who are reading this for information because you are newly diagnosed, I learned a pretty valuable lesson. Don't just go with the flow and trust you are being led in the right direction. Learn as much as you can as fast as you can and get a second opinion before any treatment is proposed. These doctors only get a handful of new ITP patients a year and they are not all highly informed or specialized. That advice is all over this forum so call me a broken record. I wish I had read it sooner but hopefully it won't make a big difference in the end with my situation.

Thank you all again!

Thanks for the update, Joel! I'm glad you had a good visit. N-Plate (or Promacta) would be a great next option for you should you need to treat. They both have a great success rate with few side effects and can cause remissions. If N-Plate works, there is really no reason to move on to splenectomy so hopefully, you won't get to that point.

Good new on the counts!

Thank you Sandi!

I guess I should also say the only weird thing now is my last two labs showed my liver enzymes really elevated. This might be due to medication. I got a pretty bad respiratory infection and was on a round of antibiotics and antihistamine the week prior. I was also having to use my asthma inhaler quite a bit which I read can do this.

3/16/16 - ALT- 178 (Normal: 11.0 - 66.0) and AST- 59 (Normal: 15.0 - 46.0)
3/23/16 - ALT-109 and AST- 36

My very first lab back in December showed slightly elevated liver enzymes but they have been normal ever since. Same with my ultrasound. Small amount of fatty liver but nothing to be concerned about.

They just called and are sending me to a GI doctor to make sure. Any thoughts or experience with random liver enzyme spikes?

Thanks!

There have been a handful people here over the years who have had fatty liver disease, not sure if that caused ITP or not. Sometimes liver disorders can cause low platelets. If your tests have been normal at times, then it doesn't seem like you are headed in that direction for now. The elevated labs could just be, as you said, related to medications and could normalize again. Hopefully that's the case!

Good luck with the follow-up. Sounds like your doctors are on top of things.

Hey guys I wanted to check in here. So it has been almost 3 months since my last round of Rituxan and I seem to be having a delayed response. Great news! My two most recent counts were 100 then 95 taken 2 weeks apart from each other.

So that is good right? Can I still see even more response after the 3 month mark? I guess we won't know if it is a short term or long term response for a while.

The 9 month mark from my last dose will be in December. So at that point I could still elect for splenectomy in a year where I have already met my out of pocket deductibles. Am I crazy to still consider that if my count dips back down to the 30's?

As I have also been concerned about additional problems resulting from the treatment, one other thing is last month both blood draws showed high Eosinophil Count. I know this has to do with allergies (and my Spring allergies are pretty bad) so I'm not freaking out and neither is the doc at the moment. I know that this can indicate beginning stages of Cushings which I developed all of those symptoms toward the end of my steroid regimen and I was on Prednisone for 4 months (last dose 4/6/16). By symptoms I mean buffalo's hump weight gain in midsection and face and neck (nothing too bad fairly mild). People can be on Prednisone for way longer than that of course. Should I be concerned or ask for any other tests? Is Cushings only something that can occure while on steroids?