TOPIC:

Ref: www.ncbi.nlm.nih.gov/pmc/articles/PMC2786288/

Hematuria (blood in urine) seems to be associated with intracranial hemorrhage, the one outcome all parents worry about... as a result, why aren't doctors doing urine analysis as a routine lab? My son's doctors never ordered it; worse yet, when his urine was checked for a separate condition (frequent urination), at the same institution, trace amounts of blood were found but neither we nor the hematologists were informed (I found out later, after finally logging into the patient portal).

If you are a parent of a newly diagnosed kid, you may want to ask about a urine analysis, and take the results into consideration when deciding on a treatment plan (or watchful waiting).

I've honestly never heard of anyone being tested for this unless they had obvious signs of blood in urine (red or pink). It's not a standard test. I think the reason is that the results could literally change from hour to hour. I think the basic thought is to look for the simple symptoms first...bruising, petechiae, bloody noses, etc and if those are minimal, internal bleeding is probably not present.

This study seems to suggest a pretty strong correlation between hematuria and ICH, so it seems worth checking, especially since a urine analysis is not invasive (and hopefully not expensive?). If the study is right, a consistent lack of blood in urine would be very reassuring to a parent. Imagine if parents could do it at home with a dipstick test to reliably confirm a low chance of ICH, I would sleep so much better at night without treating low numbers. (Yes, seeing positives would probably increase treatment rates, but if further research were to confirm the correlation between hematuria and ICH, perhaps that wouldn't be such a bad thing.)

This is another interesting article (literature review), which discusses the topic, including the limitations of the study above, and some new findings (e.g. increased reporting of hematuria in recent years, and the novel practice of tracking "microbleeds"):
www.sciencedirect.com/science/article/pii/S0037196313000255

You could talk to your doctor about it if it would help you to feel more comfortable. It is inexpensive, that's true. It's not unusual though to find trace amounts of blood in urine so I'm not sure what the cut off would be when you'd need to worry. How often would you want to have it done?

How are his symptoms, btw, since the IVIG?

All very good questions. The study needs followup, for sure. There are some warranted questions around limitations. What if the reporting was generally / somehow more meticulous in the ICH group than the control, which had zero instances of hematuria?

As for applicability, I have no idea what the cut off would be or how often one could do it (if there was a home dipstick test, it would be easy to do even daily, at least for my 3 year old who still insists on using his little potty and not the adult toilet)... I just get the feeling that a lot more could be done to make management a bit more predictable. I grew up with asthma, and I remember being followed much more carefully in terms of tests, and my parents having much more precise advice about what to do in case of an attack...

Thanks for asking - he has been doing great since the IVIG a week ago, with zero symptoms until today, when I noticed a tiny line of petechiae from scratching, and a bit of reddish nasal discharge, no actual blood. It's great to see his skin totally free of bruises. We'll likely do a count on Wednesday when he goes for a checkup. I hope he holds up for a while, symptoms wise. He is big into attempting headstands on the bed, which I used to encourage but now terrifies me, so I've tried to distract him from attempting them...

Here is another study, on occult hemorrage:

onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.24264

"Our findings suggest that occult hemorrhage occurs with greater frequency than overt bleeding in children with severe ITP. CNS [cranial nervous system] microbleeding is a potential risk in this patient population. "

Talk to the doctor, Maria. I think you're freaking yourself out a bit with these articles. Not that there isn't anything to worry about, of course there is, but the only way to really control that is more frequent counts and treatment.

Don't worry, I'm totally calm, just frustrated. More frequent counts are not great for little kids so if there were better ways to track symptoms, it would greatly improve quality of life at least for pediatric patients.

Apparently platelets also play a role in vascular integrity (ie it's not just that if you do bleed, it may not stop, but it may be easier to begin bleeding for ITPers in the first place):
www.ncbi.nlm.nih.gov/pmc/articles/PMC3229170/

PS This is not to panic anyone. As a friend of a friend who is a hematplogist told me the other day, "the prognosis for ITP is super."

Vitamin C is known to strengthen the blood vessels and vascular integrity. Just an FYI. It has improved symptoms for some people over the years.

Yes, spontaneous bleeding is always a possibility, but is very rare. Again, symptoms are usually a good indicator of how well the body can tolerate low counts. There are other clotting factors in addition to platelets, and many ITP patients have 'microplatelets' that are too small to be counted but aid in clotting. It is thought that platelets shatter for some reason and those tiny platelets do work.

"Platelet microparticles (PMPs) are vesicles derived from platelet membranes that are too small (less than 0.5 micron) to be detected in routine platelet counting. They arise in association with platelet activation and other unknown causes. Elevated PMPs have been observed in idiopathic thrombocytopenic purpura (ITP), a disorder in which autoantibody interacts with platelets and the opsonized platelets are destroyed by macrophages. However, the clinical significance of PMP has been unknown. Using flow cytometry, we examined PMP concentrations in 62 patients with ITP and in 33 normal control subjects to assess the clinical significance of PMP in ITP. When compared with PMP levels in control subjects, PMP levels were significantly higher (p less than 0.005) in patients with ITP, but considerable variation among individual patients was observed. Patients with platelet counts less than or equal to 60,000 were evaluated for correlation of PMP levels with manifestations of thrombocytopenias; patients without symptoms (free of petechiae or mucosal bleeding) are found to have significantly higher PMP levels (p less than 0.05) than patients with symptoms, suggesting hemostatic protection by PMP. Additionally, we identified a group of patients with ITP who experienced neurologic complications resembling transient cerebral ischemic attacks (TIAs): recurrent episodes of dizzy spells or weakness in mild cases, and coma, seizure, or progressive dementia in advanced cases. Small cerebral infarcts were demonstrated by computed axial tomography scan or magnetic resonance imaging in spite of severe thrombocytopenias. Patients with this syndrome are often found to have higher PMP levels (p less than 0.005) when compared with the group free of neurologic complications. It is concluded that PMPs play an important role in hemostasis in patients with thrombocytopenia, and that high concentrations of hemostatically active PMP can be thrombogenic in certain clinical settings. Quantitation and characterization of PMP is important in assessment and management of patients with thrombocytopenia. "

www.researchgate.net/publication/21573113_Clinical_significance_of_platelet_microparticles_in_ITP

That's just it, though, outward symptoms seem totally useless as predictors of ICH, if the study from my first post on this thread is to be believed. Only head trauma and hematuria were significantly correlated with ICH; bruising, petechiae, even nose bleeds, were not.

That is totally fascinating about the microplatelets. I think I found my bedtime reading for tonight! Thanks!

And I've read on this site about vitamin C, and will look into it some more. How much vitamin C does one need? We eat a lot of fresh fruit and veg.

I don't know how much Vitamin C to give a child. I take 2,000 to 4,000 mg's daily which is about all I can tolerate without running to the bathroom. A person can never have too much, so it depends on how much can be tolerated.

This doctor gives fantastic speeches about Vitamin C and the benefits to the body:

www.youtube.com/watch?v=y0LLX0sgwAU

www.youtube.com/watch?v=JFT5rdwrNV0&t=588s

Maria - all of us, for years, have solely relied on outward symptoms to base treatment decisions. I've been here almost daily for twenty years (yikes) and that is all we've looked at. It's worked pretty well for most of us. Your article about the urine was the first I'd heard of it. Talk to the doctor and see what he says. I'm kind of curious to know too. Apparently, not many doctors have read that because it hasn't been put into practice based on what I see here.

Thanks, Sandi! I will check out the vitamin C stuff!
I'll definitely ask the doctor about the hematuria. That article is the only one I can find too, but it has been cited by a lot of others. It's a bit strange no one has tried to replicate the results, it should be relatively straightforward. I am guessing the issue is, as you said, that no one gets tested for this routinely, so there is little reliable data. Still, with tens of thousands of people having ITP in the US every year, I can't imagine it would be very hard to do a 3-5-year study with a decent sample. You'd need records of ~10,000 people to possibly see 50-100 cases of ICH (assuming an incidence rate of 0.5% or less). I kinda want to quit my job and run the study, just so we can have an answer, ha! (Actually, it may be even easier to get to those numbers of participants if we allow other thrombocytopenias, although of course that wouldn't be as accurately applicable to ITPers.)

It would be an interesting study! The downside is that to prove the point, you'd have to witness ICH in the patients. We don't want that to happen!

I dunno. Previous to your posting Maria, I just assumed one would have a headache if there was a brain bleed.
Also, if one had a headache, and normal headache drugs weren't effective (excedrin is a sure headache kill for me), then that would be reinforcing evidence of bleeding.

About doing a study. Give it a couple of months. You'll probably come up with an even more provocative study at this rate. As they say, 'choose your battles wisely'.

Oh BTW. I came across this statistic that I was trying to remember before. ASH is the publisher here too.
Diagnosis and Management of Immune Thrombocytopenia in the Era of Thrombopoietin Mimetics
"Approximately 65%-70% of children remit by 6 months and another 15%-20% by 12 months."

I get the impression that the Thymus is very much trying to figure out what is bad and what is good during the formative years - hence this statistic. Later, the gland becomes less plastic as we grow older. Thus, may need a very powerful immune system provocation/inflammation to get a Shingles vaccine to 'stick' in older folks.

I think it would be hard to determine headache severity in a child who cannot verbalize it as well as an adult. I've heard it described as a 'thunderclap headache'.....it comes on fast and hits hard, like you got hit in the head with a baseball bat. It's nothing that you'd sit around and wait for Excedrin to kick. Normally there are other symptoms such as vomiting and loss of use of one side of the body. It's literally a stroke. Hemorrhagic as opposed to ischemic.

Right! The point of the study would be to find better ways to reduce the already low (but not low enough in my humble opinion ) percentage of ITP patients at risk of ICH. Presumably, around 0.5% (according to current estimates) will end up with ICH --whether they are being studied or not (so we may as well study!).

As suspected, the doctors hadn't seen the study. To their credit, they said they'd be happy to repeat the urine analysis next time his other symptoms were stronger and/or count lower.

Maria - I'm not surprised that they hadn't seen the study. At one point, my Hemo told me that I knew more about ITP than he did.

I watched a documentary tonight on Netflix. It's called The Bleeding Edge. Nothing about ITP or bleeding; it focused on medical advances. It's a real eye-opener. If you happen to watch it, let me know.

A couple of quick questions for you Maria.
Would it be reasonable to expect those with low micro platelets to be most at risk to bleeding/ICH?
Would one expect the quantity of micro platelets to be related to which antibodies were in play? That is, are micro platelets created by imperfect destruction - partial platelet destruction creates them?

Hal, these are super interesting questions and my answer is the same for all: I have no idea.

Sandi, that documentary sounds intriguing, I'll look it up if I get the chance!

Hal.
1. Yes. That's been mentioned in the data.
2. I suspect it would be a destruction issue, but I don't know if they have identified antibody causes yet.

Maria,
My son just diagnosed for ITP about a week ago, you could see my post here
pdsa.org/discussion-group/12-newly-diagnosed/30194-11-years-old-son-just-diagnosed-with-itp.html

I just read your post and found it is interesting. My son's platelets dropped to 3K this Friday at our Hematologist's office. So he send us directly to Children's National at DC to do another round of IVIG. At the same time, he also ordered a urine test. Neither he nor hospital doctor mentioned to me anything wrong about urine test. When we discharged from hospital today I asked for a copy of all test results. Then I noticed that my son's urine test shows 2mg/dL blood. It is just a trace amount and not visible to human eye. I asked hematologist in hospital and he said it is very common to have trace amount of blood with low platelets and nothing to worry about. After read your post, I will ask our hematologist again this coming Monday.

TH, we were told the same thing. On the repeat analysis, it was OK. The patient portal at Children's is kind of annoying, eh? (Yes, I'm Canadian!) They embargo the results for too long and then you have to click on all the individual results..

Chidren's has a portal? They never mentioned to me. Just want to make sure that we are talking about the same hospital. We were at Children's National Washington DC US.

Yes. childrensnational.org/specialty-care-patients/manage-your-care/patient-portals
You have to register for it while you're at the clinic. You can ask the young man at the front desk (the one who sits near the fish tank) to send you instructions by email.

Thanks for the information. We are going to Children's National Outpatient Center at Rockville Maryland today for follow up (I am living in Montgomery County) and will ask for instruction.