Question about treatment course

My husband was diagnosed at 18 and was stable for 10+ years but the middle of last year he started bruising badly. We were lulled into a fall sense of security by his relatively stable and high counts (90s-110s consistently) for so long and honestly very ignorant of how bad things could get so he didn't see anyone about it for months. In December, I had a friend order a CBC for him thinking we would just check and see how he was doing. The count came back at 1 and it's been an odyssey of hospital stays, ER visits, treatments and doctor visits since then.

His doctor to me seems a tad splenectomy happy. Some testing/treatment options have been due to my research and asking for certain things. Thus far he only has small, almost negligible responses to Dexamethasone and prednisone. They did a two week cycle of abx because he tested positive for h pylori. During his last hospital stay, they gave him multiple rounds of IVIG and two platelet transfusions and he was released at a count of 17. Insurance approvals have held a lot of things up and been an all around nightmare so we are just now trying his first week of Rituxan. That's some background to get to my question.

His hematologist says if he hasn't responded in 8 weeks she wants to start the preparatory round of vaccinations for a splenectomy. I am a little confused because I thought Rituxan removed immune memory and vaccinations wouldn't take. She offhandedly mentioned Promacta but said she doesn't think that is a good idea. We are really, really hoping to avoid splenectomy so I am not sure why she doesn't want to try TPO-RAs, unless it is because he destroys platelets so quickly that she doesn't think making more platelets would help. He has currently had single digit counts for weeks and they are doing platelet transfusions multiple times a week, but his body destroys them all in <24 hours. Am I on the right track with assuming the Promacta won't work because of his platelet destruction issues?

Any insights would be appreciated.

Welcome ten-eyes,

You have really done your homework. You might read up on retesting for h pylori, as I recall it can be resistant to certain therapies, and require retreatment with different antibiotics. Also, platelet response to h pylori eradication takes anywhere from 1 to 6 weeks from treatment.

8 weeks is early to give up on Rituxan. 12 weeks is common, and delayed responses do occur even later.

You are right about the vaccines. Here is a good reference on that:
www.bloodjournal.org/content/122/11/1946?sso-checked=true
6 months is generally considered the duration of B-cell depletion, and some vaccines give poor response even later than 6 months.

Platelet transfusions are CONTRAINDICATED except where actual bleeding is putting life at risk, and cannot be stopped by other means. Exogenous platelets stimulate the immune system to fight platelets, and each transfusion shortens the amount of time before the next transfused platelets are destroyed. Platelet transfusions should be reserved for life-saving measures and for emergency major surgery.

ITP can be caused by either poor production or excessive destruction, or both. Destruction can occur while platelets are being created or afterward, when they are in the bloodstream. Promacta accelerates production, which can help if your husband is producing too few platelets. It can also help where destruction is the problem, by producing platelets faster than they can be destroyed. I have not read of there any way of knowing whether TPOs will work except trying them.

Are all of his other blood studies coming back normal?

From several things your hematologist has said, I am not too confident in her. Maybe a second opinion would be a good idea, from someone who is highly knowledgeable with ITP. Where are you located? Maybe someone here can refer you to an expert.

For those who didn't get why I called you ten-eyes, a bee has five eyes, so a bee with glasses (bee-spectacled) would be called ten-eyes instead of four-eyes. :woohoo:

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Hello Bee. Welcome to the group!

I agree with everything that Rob said. I also think a second opinion is in order. Promacta and N-Plate have done wonders for many seemingly refractory patients, so I do not think it is unreasonable to give it a try. Most people respond well and it has been a great addition to ITP treatments. It is sometimes the only thing that works for some people and seems to have very few side effects. One unexpected perk that came from the TPO's are remissions. Some people are able to eventually stop using them even though many patients and doctors assume they will be used for life.

It's true that vaccines are usually not effective after splenectomy, yet I see this happen time and time again. Patient gets Rituxan and has no response after a few weeks, so they are pushed into the surgery. It's frustrating to see that the literature is either ignored or unread.

People can also become refractory to platelet transfusions, so they should be reserved for bleeding situations.

There is another gentleman here who had the same situation as your husband. He was in single digits for months until he started N-Plate. His counts are now great and he is doing well. He never thought he'd get to that point and felt discouraged. The TPO's can work even if destruction is presumed to be the problem. It's possible that your Hemo doesn't have any experience with the TPO's and wants to avoid them for that reason. That seems unfair to the patient since you have every right to explore any treatment method that is a viable option.

Homework is my preferred coping mechanism in scary times.

We are in Phoenix, AZ. He has an appointment scheduled for a second opinion with a doctor at our local Mayo Clinic early next month, but I don't know how well versed that particular doctor is in ITP, either. The more time I spend on the PDSA site/forums the less I find his current/recent treatment course evidence-based. It seems like a very old school approach, but with his counts staying in the single digits and the looming fear of another bleeding episode/hospitalization I'm afraid my husband will just go with the flow out of desperation. I really don't want him to lose his spleen just because we didn't see the right care provider.

It sounds like I need to do more research on Promacta.

Bee, You can click on "search" and plug in Phoenix to find comments related to others in your area.
You can click someone's name, then the "message" tab to send a private email, since not everyone checks in every day.
There is a local group in your area:
pdsa.org/join-the-community/local-groups/item/472.html

Just think of it this way: if he would have a splenectomy out of a sense of urgency and it didn't work, what would you do next? Do that now.

How are his symptoms, by the way?

I emailed the contact for our local support group to see if there are any local doctors that they could recommend. Here's hoping!

Do you have any literature/studies with the platelet transfusion info? I showed him your responses and he said it sounds like he should refuse further platelet transfusions unless he is emergently bleeding. I thought he might feel more comfortable saying no if he goes armed with evidence.

Symptom-wise, he is currently dealing with a persistent low flow nose bleed. I suspect that is mostly caused by our dry climate and winter heater usage. He isn't even bruising nearly as badly as he was last summer, but he is also not doing a lot of the things he used to do that might cause bruising. He often seems very fatigued, but that seems more related to a) the steroids making him so agitated he can't sleep well at night and b) after effects of the various transfusions/infusions.

From my perspective, the low counts are hitting him almost more emotionally than physically. He doesn't like feeling fragile. If we could just bump him up to the 20s even, I think a lot of the urgency would disappear.

Rob16 wrote:
Are all of his other blood studies coming back normal?

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Forgot to respond to this bit. I'm not sure, is the short answer. I know his dr. has run a billion things, but I don't know what would be relevant to your question.

Immune Thrombocytopenic Purpura Treatment & Management
Platelet transfusions may be required to control clinically significant bleeding but are not recommended for prophylaxis. Transfused platelets also have decreased circulation, and repeated platelet transfusions may lead to platelet alloimmunization.
emedicine.medscape.com/article/202158-treatment

Too tired to find primary sources, but secondary sources like this one are all over the place if you google: alloimmunization platelet transfusion ITP

Rob16 wrote: ITP can be caused by either poor production or excessive destruction, or both. Destruction can occur while platelets are being created or afterward, when they are in the bloodstream. Promacta accelerates production, which can help if your husband is producing too few platelets. It can also help where destruction is the problem, by producing platelets faster than they can be destroyed. I have not read of there any way of knowing whether TPOs will work except trying them.

Here's a study I found on this subject, titled Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists.
www.ncbi.nlm.nih.gov/pubmed/23913253
I have no expertise to understand how significant it is, but thought I'd add the link for others' evaluation.

On a personal note, my ITP worsened enough to need treatment in August 2013. After taking prednisone for 14 months, it began to work only sporadically. My hema kept pushing for splenectomy, but I kept pushing back harder. During the past 12 months, I've had five different MDs try to convince me that splenectomy would solve all my problems. I adamantly refuse to consider it, given the meager success rate for someone my age.

Doctor Hema finally convinced me to try Rituxan, and I very reluctantly agreed at first. At the very last minute, I backed out. The severity of possible side effects seemed worse to me than the risk of ITP bleeding. I then consulted a top university ITP specialist who, to my amazement, also pushed splenectomy.

I finally opted to try NPlate. With its 80% success rate and very low complication rate, it seemed my best choice. I started treatment in October '14. Am still trying to get off the prednisone and stabilize to a safe count; but I'm sure it will be done with enough patience. It does bother me a bit that it is still a 'young' drug, but I'm not sorry to have begun it.

I've had ITP since late 2008. I don't pretend to understand a fraction of the science of it the way that Rob and Sandi do; but I've done quite a lot of reading, researching, and treatment consideration. I wouldn't consider your husband's doctor to be up on her game with this disease. You'd be wise to seek other opinions until you find options that are more acceptable to you both.

Bee:

I wouldn't go to the Hemo with a handful of responses from people on a message board. It's not very credible to any doctor. You'd need better sources such as Bloodjournal or the NIH.

Bee, My google-fu has failed me: I cannot find primary research for ITP patients developing immunity to transfused platelets. It is something that seems to be accepted as fact in MANY articles, like the one I showed above from Medscape. The phenomenon was noted in early research on platelet transfusion by Hirsch and Garner, 1952 but I cannot find a copy (too old?).

I would go with the Medscape article.

Here is some info from the International Consensus:

Emergency treatments

An urgent increase in platelet count may be required for some thrombocytopenic patients needing surgical procedures, at high risk of bleeding, or with active central nervous system (CNS), GI, or genitourinary bleeding.

Although changing from corticosteroids to IVIg or anti-D may be effective in emergency settings, combining first-line therapies is appropriate: prednisone and IVIg are recommended for the emergency treatment of patients with uncontrolled bleeding. High-dose methylprednisolone (HDMP) may also be useful in this setting. Other therapies that work rapidly include platelet transfusion, possibly in combination with IVIg, and emergency splenectomy. There is also some evidence of rapid response to vinca alkaloids.

www.bloodjournal.org/content/115/2/168.full?sso-checked=true

Platelet transfusion should not be considered benign and should be withheld unless there are compelling clinical indications, and these usually involve current serious bleeding accompanied by thrombocytopenia below 50,000/µL or platelet dysfunction. Serious bleeding is almost never explained primarily by thrombocytopenia with a platelet count that is between 50,000 and 100,000/µL in our clinical experience.

www.ncbi.nlm.nih.gov/pmc/articles/PMC2874899/

Sandi: I laughed a little at the thought of saying "The Internet people told me..." I assumed that wouldn't go over well. He says he is comfortable just outright refusing because they're obviously not helping anything based on his counts, so I guess that is what he is going to go with. I pointed out that if he gave her scholarly info on why he doesn't want to, he could possibly help a future ITP patient that crosses her path, so perhaps he might.

Rob: already excerpted the medscape article for him and I'm hopeful it is enough to at least get her thinking/researching. I tried digging last night as well, but mostly only found general articles about alloimmunization and a few mentions of not using platelets in non-emergent bleeding situations in patients with ITP but no real "why" links. There were also some that said it could be used preventatively in patients with extremely low counts though. I might feel differently about it we weren't adding the risks with what appears to me to be an absolutely negligible benefit.

Thank you all for the advice thus far. In a strange way, I have found it a relief to have my concerns about his doctor confirmed. It gives me hope that just because he has not responded well to the things we have tried so far that that doesn't mean he won't respond well to the other options. After a few months of nothing working, it can be easy to feel like nothing will work. So thank you all for that.

Bee,
From my experience I can recommend NPlate with the only side effect being a mild headache. It might take a few treatments (5 weeks for me) before it works as they start you off on a small dose and gradually increase it but once it kicked in I never looked back and went into remission on the 5/11/4 after 5 months. I was refractory to all other treatments and was below 5 for many months but now I do not take any medications and have maintained a 200+ count. Just be prepared for some scary platelet counts though while they balance dosage levels to platelet numbers (my max was 1,084 but I felt no different than when I was at 0) as the difference in the dosage level amounts is very small. I was losing between 150-250 platelets per week and it was only NPlate that saved my spleen as that was becoming my last option.
I wish you all the best.

Bee:

There is always hope. Always.

Here's a couple of options (my preferred search is "benign hematology" to find docs who know about ITP)

arizonaoncology.com/physicians/profile/dr/

azcc.arizona.edu/patients/directory/Physician?tid=369&field_profile_specialty_value_many_to_one=All&site=All (picture of the doc returned when searching thrombocytopenia is attached)

Bee
I am in scottsdale and would love to talk to you! I see dr. Halepota at palo verde cancer centers and am getting a second opinion at ironwood cancer center on wednesday. Maybe sandi can tell us how to actually talk to each other without disclosing personal info on the discussion group. I am really new to ITP and have fingers crossed the nplate works for me. Just finished the steriods and have horrible indigestion. Not sure if it is nplate or left over steriods. Sleeping better and my emotions are back in check.

Emily:

To speak to Bee privately, you click on her name (left side, above picture) and then click on messages. You will be able to write a message that will go directly to her e-mail address.

So, an update. He had a CBC this morning before the second week of Rituxan and his platelets are at 4. They wanted to order another platelet transfusion for him but he refused it and they said that was fine since it didn't seem to be helping anyway. I'm starting to feel like they're ordering things just to have something to do. They're doing two rounds of IVIG instead, which feels a little futile to me as well since he seems to be refractory to those as well.

His dr stopped in during the treatment to talk to him about it and said she is very concerned about how low he has been for so long and she *really* wants him to have a splenectomy. He asked her about why she doesn't want to try a TPO and she said that they can cause bone marrow fibrosis and he can't be on them for very long. I guess I need to do more digging into the side effects because her new plan is if he doesn't show a response to Rituxan by week 3 she will concurrently put him on a TPO as well. He is concerned that they won't know which he responds to if he is on both.

Is there anything that can predict the success of splenectomy? I thought I saw something about a platelet localization study or something named similarly that could. We are just so concerned about splenectomy happening and not having any effect on his counts.

Thanks again for letting me pick your brains on this.

Did you bring up the issue of vaccines before splenectomy?

It is called an "indium-labeled platelet screening test" Available in England and at one place here... I think Johns-Hopkins. (somebody please confirm)

I do not see any reason not to start Promacta. The strategy is to adjust the dosage to keep platelets at or below 50k. If the rituximab kicks in the dose will drop to zero, and you will know.

The indium screening test determines whether platelets are being sequestered in the spleen or in the liver. If in the liver, splenectomy will not help. If in the spleen, splenectomy MIGHT help.

Rob16 wrote: Did you bring up the issue of vaccines before splenectomy?

It is called an "indium-labeled platelet screening test" Available in England and at one place here... I think Johns-Hopkins. (somebody please confirm)

I do not see any reason not to start Promacta. The strategy is to adjust the dosage to keep platelets at or below 50k. If the rituximab kicks in the dose will drop to zero, and you will know.

No on the vaccinations. He goes to his treatments by himself because I'm at home with our kids and so the vast majority of his interactions with his hematologist occur when I'm not around and remembering all the questions/issues I pepper him with is not his strong suit. Especially since the steroids seem to exacerbate his ADD. It will definitely come up if we proceed any further towards splenectomy (or vaccinations) but for now he stood firmly that he wanted to try TPOs before splenectomy.

Now to win the Powerball and fly us all to England.

You are so right about steroids making ADD worse. I also have a spouse with ADD and ITP who can't remember to ask all the right questions, and it definitely gets worse with steroids. I can think of a number of ITPers on this website who I'd bet have ADD. Do you think there might be a connection? :lol:

OCD here, no ADD!

SO far with the TPO's, bone marrow fibrosis has been reversible once the drug is stopped. It does not occur often, and many people have used the TPO's for years without having problems. Some patients have even gone into remission after using N-Plate or Promacta for 2 or 3 years. The main thing with those meds is that counts should be around 50k; you don't want to maintain normal counts.

The only problem with Rituxan and a TPO is, as you said, you wouldn't know which is working. If counts go up, hopefully the doctor would know enough to back off the TPO dose.

There is no way to predict splenectomy success. Rob mentioned the indium-labeled platelet screening which is performed in the UK. I haven't heard of anyone having it done here in the US. The test can tell you where destruction is taking place, so if it's in the liver, splenectomy will not work. If destruction is shown to be in the spleen, a splenectomy might work. The liver can take over destruction so going by what the test shows is not a sure thing, plus having the answer will not help if production is the bigger problem. I sometimes wonder if that is the case when people do not respond to treatments that target destruction, like steroids.

How are his symptoms through all of this?

So something changed in the doctor's demeanor since this morning and she called him back after the Rituxan for another sitdown. My husband has had single digit counts now for... I want to say about a month. She has been okay with him doing outpatient treatments up until today. For some reason, despite them being consistently this low she seems totally freaked out today and was saying he can no longer drive anywhere alone, she would really like him hospitalized for constant monitoring until they go up and she is trying to get him the NPlate today and probably moving up how long she wants to give the Rituxan to work. She also was shocked he was still going to work, but calmed a bit when he told her he was just sitting at a desk all day.

I'm not sure why today is her breaking point so to speak, or if we have just not been appropriately alarmed by his counts. He told me he is now "super scared."

Sandi: He still has a nosebleed on and off, but it is very mild. I think it is mostly because we live in an extremely dry climate. He also had some new bruises pop up but he has had far, far worse. He's also fatigued, but he doesn't sleep well on the 40mg of steroids he's been on for the last two months, so I don't really know if that's the ITP or the side effects talking. When he was initially discovered to have single digit counts he wasn't feeling fatigued at all.

Bee:

I've always said that the reaction of the doctor will set the tone for the patient. It sounds as if his symptoms are not too bad, and that is the main thing to focus on. At this point, it wouldn't hurt to try the hospital and see what they can do, although there isn't much they can do for him there that they haven't already tried outpatient. Good news on the N-Plate though, let her get moving on that. It can take a few weeks to work, so don't expect much right away.

www.healio.com/hematology-oncology/hematology/news/print/hemonc-today/%7Bb11cec31-e0a4-4c96-89e0-d441862c9e10%7D/eltrombopag-maintained-efficacy-after-cessation-in-immune-thrombocytopenia

I think part of it may be that is is a very "still waters run deep" kind of guy who doesn't wear his emotions on his sleeve. I'm getting all of this secondhand through him, but it felt very much like she doesn't think he is reacting with enough concern and she may be thinking he's not taking it seriously and wants to shake him out of that. Which is totally not the case at all, but a relative stranger could get that impression from his outward demeanor. That and based on some of her past comments I think she thinks if he understood the gravity he would have agreed with her on the splenectomy already.

I really felt like his symptoms were mild and nothing at all has changed with them in the past few weeks, so today's change of heart is kind of baffling me.

I'd bet dollars to donuts that it is the fact that he is resisting the splenectomy.

What ever happened to the idea of a second opinion? That would become more difficult once he is in the hospital.

I agree with Sandi: it is good to get started on the N-Plate.