Husband Newly Diagnosed.ITP & Heart Transplant

husband just diagnosed 12 days ago, has been in hospital due to only 2k platelet, he is 67 yo, has heart transplant 10+ years. was on Prograff, just changed to Cyclosporin to treat ITP. 3 days of massive dose steroids (increased count to 21k but didn't hold). Then 2 separate IVIG treatments over about a week with 2nd pushing up to 31k, the highest since admitted. We r waiting to hear whether it held which will be good news and allow us to go home. drs. say probably will do Retuxib soon either here at hospital or at home if platelets hold at 31k and/or goes up.

This could have been triggered with a cold he had before for 2 weeks, which he probably acquired from me (I had for a month and couldn't get rid of). He was on his 2nd round of antibiotic, and mine had seemed to go away after 2 weeks and return or either he gave it back to me. Who knows. Here in Atlanta area we had an unusual 3 weeks of no stop rain with all the usual high pollen etc. I had begun gardening and wondered if all the exposure to flowers breathing in pollens everyday etc had led to just allergies of which I have never experienced to that magnitude. No matter, don't know if any of that led to anyof this, but he had never experienced such a low platelet count before although hovering in the 95k-130k since 2012.

all his vitals have been good now for last 3 days. He did have a low BP episode, going down to 71/49 which is was in hospital room and ran to nurses station for 2nd time warning that his BP was going too low. A code was done with hydration infusions and 02 which brought him back. That sure was frightening. Really, since it was just the following day after fIrst IVIGi fusion, high BP was expected instead. Therefore, suspicion of infection led to transfer to CCU and 2-3 days of IV antibiotics. No infections whatsoever have been found since the beginning and many, many tests have been performed.

Any helpful info would be appreciated.

Hi Sharon. Sorry to hear about your husband.

The first thing that you should know is that low counts themselves are not necessarily a life-threatening thing. The symptoms are more important. How does he do with counts under 10k? Does he have any bleeding?

It could have been the cold that triggered this, but it also could have been the antibiotic. Drugs can sometimes do that, especially antibiotics. It could also have been the combination of events. You never know. Sometimes ITP is acute and goes away within a few months to a year. Only time will tell if that is going to happen or not. In the meantime, you just have to manage it the best way you can to keep counts in a safe range. 'Safe' usually means anything over 20k to 30k. Most people do fine with counts in that range and 'normal' counts are not necessary. Some of the treatments can cause remissions. IVIG is not one of those treatments; it is just a very temporary rescue treatment. Rituxan is one of the treatments that can cause remission if a person is responsive to it. Some people do respond and some do not.

I don't know if his heart condition complicates his situation in any way or not. It might affect treatment decisions and hopefully, you have a good team of doctors working for him. Many Hematologists are not well-versed in ITP and it can sometimes be a challenge to find one who is.

There are quite a few more treatments to try and it wouldn't hurt to become familiar with them and possibly make suggestions. Some have worse side effects than others, some have better success rates than others. There are many experiences here that you may benefit from if you read them. Most people end up becoming ITP experts in a short period of time.

Someone posted this story a few days ago. It is definitely worth reading.

ouhsc.edu/platelets/ITP/crystal.html

Thanks for the input! He did have another improvement today from 31k to 37k. Hematologist was pleasantly surprised. Didn't mention in my first post that he did have significant bruising along with some of the red dots and a huge bruise on his backside that never had any pain and didn't know was there until night before visit to ER. Also had some bleeding at night sleeping which he thought he was biting his tongue sleeping and re injuring original bite. In hindsight, these were symptoms of course. Bleeding issues subsided quickly after hospital admittance.

Will do the Retuxin on Monday. Also, I forgot to mention he has Diabetes 2 which he acquired post transplant.

He has having been having high BP issues in the last 2 days. though glucose excellent, heart rate and 02 very good. From what I understand the Retuxin destroys the B cells responsible for attacking the platelets? Also, I have read he could have a harsh reaction to Retuxin, and so I have requested that he stay in the hospital at least until after the following day of the infusion in case he becomes very ill. There is only so much I can do at home, plus don't want to rush back to hospital several days later if doesn't go well. At least that is my thinking at this time. If anyone has any helpful comments, please let me know. Either here or at. Sharonwo37@yahoo.com

Thanks

Hopefully, he will continue an upward trend. Platelet counts can fluctuate constantly, so the numbers can change even in a few hours. The analyzers that count platelets also have a margin of error of around 5k, so even the same blood sample run twice can show two different numbers, such as 17 and 22. Counts bounce around a lot with ITP.

ITP bruises usually don't hurt; we've all said that at one point. I once had a huge black one on my thigh that looked like it would really hurt if touched, but it didn't. It was as black as a rotten banana. Probably because there is never any actual trauma to the area...it's just a spontaneous thing.

The main symptoms to look out for are 'wet' symptoms, such as blood blisters in the mouth, blood in urine or stool or a nose bleed that will not stop gushing.

Good luck with Rituxan. The list of side effects is long and ugly, but most do fine. I'm sure they will want to monitor him extra closely because it can cause cardiac or blood pressure issues for some people (normally only during the infusion). It can take a few weeks to begin to work, usually between 4 to 12 weeks, so it's a treatment that requires patience. You're right about the way that Rituxan works. Many people with ITP also have platelet production issues too; destruction is not the only cause.

Managing ITP when other conditions are present can be tricky at times, like the steroids and diabetes/high blood pressure. If those continue to get worse, other treatments can also be considered. I hope he has a good team of doctors that communicate with each other. It will make everything much easier.

I didn't realize it takes 4-12 wks to work. I read about Nplate and another and wonder if those have a better track record? Though they likely have specific reasons Retuxin was chosen, I imagine?

Yes, he has Hemotology, heart and endocrinology Drs. Also numerous fellows, interns, residents (Emory is s teaching hospital). All of whom are in communication with each other here at Emory. He seems to be receiving excellent care. Today all his vitals are very good and stable.

Yes, N-Plate and Promacta have better success rates than Rituxan. It wouldn't hurt to ask why they are going this route with Rituxan.

After doing some reading, it looks like the Nplate is really only to maintain at 50k (he is only at 37k now though) and the Promacta poses increased risk of blood clots which is probably why don't want to use. however, it is likely there are other reasons due to being a heart transplant recipient, blockages, and other medical issues he has to use the Retuxin instead.

Sharonwo37 wrote: however, it is likely there are other reasons due to being a heart transplant recipient, blockages, and other medical issues he has to use the Retuxin instead.

That could very well be. Both N-Plate and Promacta use pose a risk of blood clots if counts are too high, and counts should be maintained around 50k when using either. 50k is a very safe count though and that is all that is really needed. Usually, the only time a count below 50k is a problem is if a person is on blood thinners. I know nothing about your husband's condition though, so of course I don't know what is best for him. All treatments have pros and cons, and most people go through a few of them before finding the one that works and one they can tolerate. It sometimes can take a year to get to a comfortable place with ITP, but some get there sooner.

Your husband's other medical issues may play a part, but 37k is not a bad count for most people with ITP and hospitalization is very rare, even non-existent for that count. Hopefully, he can get out of there soon! I hope Rituxan goes well.

Platelets Up to 40k today. We r waiting in our room for the Hemotologist to come talk to us re: Retuxin. Given husband's numerous health issues, we may forgo Retuxin temporarily, but will see. the gradual increase that has occurred this week since the last IVIG infusion instead of decrease is promising it seems. then again, if the Retuxin works as it should, it will erase the autoimmune memory forever, at least, this is what I understand and want to delve further about this with the dr.

No, Rituxan does not deplete memory cells forever. It only targets CD20 cells which are cells that are already present in the blood. B cells that are in the bone marrow or brand new baby B cells that were just produced do not have the CD20 marker. They will regenerate and it usually takes about 9 to 12 months to have a normal level. This is why Rituxan remissions usually last about a year, give or take.

This article uses the exapmples of lymphoma and RA, but it also applies to ITP:

Rituxan is a therapeutic antibody that binds to a specific protein called CD20 found on the surface of cancerous and normal B-cells. In non-Hodgkin’s lymphoma (NHL) and rheumatoid arthritis (RA), Rituxan works with the body’s own immune system to eliminate marked CD20-positive B-cells. Stem cells (B-cell progenitors, those cells that give rise to B-cells) in bone marrow do not have the CD20 protein. B-cells usually regenerate after Rituxan treatment and return to normal levels in about 12 months for most patients.

media.biogen.com/press-release/corporate/fda-approves-rituxan-plus-chemotherapy-most-common-type-adult-leukemia

Note: The B cells that are eliminated are not specific B cells that target cancer or ITP. Rituxan reduces the general population of all B cells that include CD20. It could take up to nine months for someone to replace those B cells and have their immune system and antibody production (including the helpful antibodies) back in working order.

www.pdsa.org/treatments/conventional/b-cell-depletion.html

My husband's father had leukemia though believed he acquired flying planes through nuclear testing in NM WW2. His son had the APS, a clotting disorder of the blood. Don't know if there is any relation at all except they are all blood disorders I believe.

Now we r being told they found a past occurrence of hep B though we never knew about at all probably from past transfusion perhaps they said? So the Retuxin may not be good for him due to risk of re activation I just read here on your site for Retuxin?

I would think that Rituxan would not be a good idea if he's had Hep B. Yikes. Yes, Rituxan can cause a reactivation of the virus. That would be a strong point to discuss with the doctors if they want to continue with it. Good thing they tested him first.

There can be a connection to APS and ITP. They can be separate disorders or they can occur at the same time. I had ITP for 8 years and then was diagnosed with APS antibodies. I've read studies that have stated that about 1/3 of the people with ITP also have APS. They are both autoimmune and it's fairly common that more than one family member will have an autoimmune disorder.

In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

www.bloodjournal.org/content/98/6/1760?variant=full-text&sso-checked=1

Many patients present with thrombocytopenia and antiphospholipid antibodies (APLAs). When both are present, 3 questions arise: (1) Does thrombocytopenia result from activation of coagulation or from platelet antibodies? (2) Do APLAs identify patients at risk for thrombosis? (3) Should treatment be altered?

www.bloodjournal.org/content/113/26/6511?sso-checked=true

Here is some info from the Rituxan site:

www.rituxan.com/?c=00001065&moc=MBRTNH7005

Sharon? How are things going?

He was released from hospital on Tuesday at 40k. Went for platelet count lab work yesterday, 3 days later, down to 19k. Told to go back to hospital. Today dropped to 13k. Hep b probably a false positive cause redid and was negative. However, will redo a 3rd to be sure as Retuxin is on the table again. Will also do a bone marrow on Monday to rule out any issues in the "factory" making area. No mouth bleeding yet like before or red spots except for the residual spots from weeks ago that partly cleared. Though I am worried about the next step since they are dropping daily and getting close to dangerous levels. I think I heard a blood transfusion may be done to get it up as it is dropping even though that was only a small increase before when done. The former 2 IVIG didn't increase platelets enough we were told today to be considered Successful. Retuxin has a 60-80% chance of working and will hold 1-2 years.

Hey, there you are! Was getting worried.

Platelet transfusions don't usually work and are actually contraindicated unless there is bleeding. Hopefully his counts will hold where they are.

I'm glad they are doing the bone marrow biopsy; that's a good idea in difficult cases. It's not as bad as it sounds. Mine took 20 minutes in the Dr.'s office. Hip is sore for a few days and bending over hurts, but the procedure isn't all that traumatic. I hope it comes out okay.

Rituxan response can be tricky. It can cause remissions with normal counts or can cause partial remissions which means that counts might just hang at a higher number than they are now. It can last two months for some who are responsive, or last years. Everyone is different. What you quoted is the average response. I did have a full remission which lasted 13 months, pretty much typical, but I have seen everything in between.

N-Plate or Promacta might be great options to discuss, assuming he doesn't have APS antibodies. It might save a lot of time waiting for decent counts since Rituxan can take so long.

The bone marrow biopsy results came Back And showed no Leukemia or cancer. Also, the Hep B was a false positive. So will receive 1st NPlate shot tonight and 1st Retuxin infusion tomorrow. Platelets have remained steady for 3-4 days at 13-15k since re hospitalized last Friday when it was 19k.

Hopefully N-Plate will work fast so he can get out of that hospital. Since N-Plate has such a good success rate though, wondering why the Rituxan too?

I believe because the Retuxin holds better and results more stable and in case it doesnt work as quickly as needed being that he is only at 13k-15k and could drop below 10k when bleeding is possible and could even be fatal. Although I am not sure about that. A bit exhausted after 3 weeks of this and a good bit of weariness going through everything waiting and wondering and so on. In other words, of the 2 treatments, chances are greater that one will work I guess???? time is of the essence too I guess is also part of the thinking????

ITP can sometimes take a long time to get under control. It can take weeks, months or sometimes a year. It is emotionally exhausting. The good thing is that it usually can be managed. Most people are not hospitalized, so I would imagine that is making things much more difficult and exhausting for you.

The problem with using both of those treatments is that you won't know which one is working. If you want to get the fastest response, N-Plate is the one to try. Some people respond well and they respond fast. N-Plate is a maintenance drug and you have to keep using it, but remissions do occur with this drug too (months or years later). Counts should be maintained around 50k and it can take time to get the dose right. Rituxan can take 4 to 12 weeks to begin to work and remissions can occur within that time period. If counts go up and the doctors believe that Rituxan is working, they will probably want to stop N-Plate. If they want to keep using N-Plate, there was no point in using Rituxan in the first place. Doing that will be like driving a manual car up a hill for the first time; you'd have to get the pedal balance right or you roll down the hill backwards. Sometimes counts drop like a rock when N-Plate is stopped, so they would have to be sure that Rituxan will hold counts up. There is no way to know that until they try. If they use N-Plate alone, they will have an exact handle on what is causing what and can adjust accordingly. Sometimes throwing too many treatments into the pot can confuse things and even cause counts to go too high.

Rituxan just seems like an unnecessary step at this point, since it is more likely that N-Plate will do what you want it to do. I think it's great that they are even using it this soon....many people go through months of failed treatments before getting to that one. It's tricky, but hopefully one of them will work soon.

I want to Reread your reply in the morning when I am more fresh minded. I believe with my husband's many health issues, heart transplant with CAV, diabetes, elderly, obese and probably others I don't recall right now, it may be felt that too low a drop below 10k would be dangerous more so than for the average person. So that by giving 2 treatments, at least one will work. I wish I understood more.

Also, it is possible that because I inquired to the dr about the possibility of using NPlate after reading your post last week that it was added to the mix, since only Retuxin had been mentioned early on as a possible treatment. Also, now that I think more about (your email-post) I do wonder if because the head dr of the Hemotolgy group has been here for 40-50 years and favors Retuxin, possibly due to the many blood cancer patients treated in the hospital environment. Nplate being the newer drug, right, is less familiar, and not used as often since ITP is more rare. Maybe it has to do with risks associated with husbands immunosuppressants, which has been changed from Prograff to Cyclosporine. his many health issues complicate treatment, I suspect, while at the same time, posing more concerns as well.

I hope you can understand my post....not sure if I was clear. My brain is fried too.

Ultimately, getting counts up is the goal. I don't know how or if low counts would affect his other health issues, so I understand wanting them to go up. But because of his other health issues, the treatments also need to be considered as a risk. With treating ITP, its all about benefit vs risk. Rituxan is an immunosuppressant. N-Plate is not.

I sure hope that this doctor is familiar with N-Plate.

Sharon - Forgive me if I get too technical, but I did find an interesting study that relates to your husband's treatment. I was concerned about the combining of immunosuppressants, so I went looking for articles where the two were combined. What I found was positive. There is evidence from a very recent study that the combination of Rituxan and cyclosporine is safe and effective:

ww.bloodjournal.org/content/early/2015/05/13/blood-2015-03-631937
A novel triple therapy for ITP using high dose dexamethasone, low dose rituximab and cyclosporine (TT4)
Key Points:

• Triple therapy is well tolerated and effective in patients with chronic ITP.
• Relapse free survival was 92% for responders after 12 months and 76% after 24 months.

The 6 month response rate was 60%, so overall, 55% enjoyed a 12 month response, and 45% a 24 month response.

Important note: the researchers used low-dose Rituxan - 100 mg on days 7, 14, 21, and 28.

The full article is not available without subscription, but here is an excellent review of it:

www.jwatch.org/na37941/2015/05/20/triple-therapy-refractory-immune-thrombocytopenia
Triple Therapy for Refractory Immune Thrombocytopenia
David Green, MD, PhD reviewing Choi PY et al. Blood 2015 May 13.
Relapse-free survival was 92% at 12 months in patients who received dexamethasone, rituximab, and cyclosporine.

Corticosteroids are the initial treatment for adults with primary immune thrombocytopenia (ITP) and platelet counts of <30 × 109/L; second-line therapies include splenectomy, thrombopoietin-receptor agonists, and rituximab (NEJM JW Oncol Hematol Jun 2011 and Blood 2011; 117:4190). Rituximab selectively depletes B-lymphocytes, but whether suppressing T-lymphocytes with cyclosporine would further improve outcomes has not been evaluated.

Now, Australian investigators have conducted a phase IIb study in which 20 ITP patients who had received ≥2 lines of prior therapy were treated with a single course of triple therapy with oral dexamethasone 40 mg on days 1–4), intravenous rituximab (100 mg on days 7, 14, 21, and 28), and oral cyclosporine (2.5–3.0 mg/kg/daily on days 1–28, titrated to a blood level of 200–400 µg/L). Additional courses of dexamethasone were given if the platelet response was delayed.

The platelet count increased to ≥30 × 109/L (measured on two occasions >7 days apart) in 60% of patients; the median time to response was 7.4 days. The relapse-free survival rates at 12 months and 24 months were 92% and 76%, respectively. Factors significantly associated with response at 6 months were male gender, prior lines of therapy, and an initial platelet response by day 28 or day 60. Therapy-related grade III or IV adverse effects were hypertension in three patients and a wound infection in one patient; there were no deaths.

COMMENT

Although the response rate in this trial (60%) was similar to that reported previously with second-line rituximab (NEJM JW Oncol Hematol Apr 2015 and Lancet 2015 Apr 25; 385:1653), relapse-free survival was longer, probably due to cyclosporine suppression of reactive T-cells. In addition, the short duration of therapy and relatively mild toxicity further commend this approach. The next step should be a phase III trial comparing dexamethasone plus rituximab with this triple-therapy regimen.

Steroids r not any longer being given to him I think due to Diabetes as early on that caused sky high insulin ranges. I can see this is a real balancing act to adjust appropriately for the best hoped for outcome. we just have to wait and go through all the motions and see what transpires. Now Having to wait another day for a Hemotology room transfer where he can be monitored closely while recieving the Retuxin infusion which could be as long as 8 hours.

Yeah, it can take a while depending on how well the patient tolerates it. Most people get it done in under six hours if all goes well. Patients are usually monitored every 15 minutes (BP and pulse) and if there is a problem, the drip is slowed. Most side effects, if they are going to occur at all, will happen during the first infusion. Once you get past that, the next three usually go fine.

He received the Nplate shot on Wed and the Retuxin infusion on Thursday. he tolerated it well. Went up to 34k and was discharged on Sat. He is at home resting well, fatigued from 22 days of hospitilazion in the last month but glad to be home.

I was wondering why?? If Nplate is the winner for getting up the count, why is it not chosen first.? you commented that people finally after failed other treatments, end up getting nplate. I know the IVIG is very costly and its success isn't always good as far as holding platelts count up very long as was the case with my husband. is it because of increased blot clot risks? If that is true, are there not meds to give that will solve that issue or is it just generally tricky when looking to prevent blood clots?

Nplate isn't used first because it's very expensive. IVIG and Rituxan are expensive too but not given every week potentionally for years like Nplate.

Yes, sadly, it sometimes boils down to money. They will spend $100,000 trying to get counts up sometimes (IVIG, Rituxan, splenectomy) only to end up with the expensive drug anyway. Makes no sense.

There are drugs that can treat blood clots, but you don't want to use them for a person with low platelets unless you have to. Blood clots can occur with low counts. You also want to avoid blood clots because they can become life-threatening quickly at times before a person can get to the hospital. If N-Plate is used correctly, the risk of blood clots is lessened.