Hydrea and Platelet reduction. What about the other blood cells?

[azaelea]

Hi, just a thought....if my platelets have reduced from 730 to 287 in under 4 months, how can they tell when they will stop going down and also if the Hydrea can deplete the red and white blood cells at the same rate, causing anaemia and immune deficiency. My next Haemo appointment isn't till 8th October ,last one being end of July. No blood tests mentioned in between. What does everyone think? Regards, Fran

[mhos61]

Interesting question.

When my platelets reduced from 500 to 288 my CNS reduced my hydrea dose from 500 mg every day to 500 mg Monday to Friday only. She did comment that she didn’t want them to go too much lower at the time.

Do you get a print out of your blood results? Just wondering if you know if your other counts have been affected.

[azaelea in reply to mhos61]

Hi, thanks for your reply. No, I don't get a print out of my blood results. I will ask next appointment. My GP was keeping an eye on them initially as my Haemo appointment was cancelled and I had to wait longer. Perhaps I should ask him to keep an eye on bloods again and have a monthly test.

[mhos61 in reply to azaelea]

I would definitely get a print out of your bloods. If you can’t get it at the hospital, ask at your GPs surgery. I always get print outs, that way you can monitor how, or if the hydrea is affecting other blood cells.

[azaelea in reply to mhos61]

Thanks. I will do this. Probably from GP's .

[WileyFrench]

Since I’ve been on HU not only are my platelets down, but other counts as well. That is one thing that seems to happen - suppress one, suppress most/all. I get tested every 6 weeks and get printed results in the mail (Canada). I just keep an eye on the red cells to make sure they’re above 110. My haemo says that below 110 might have to look at iron supplements or something.

[azaelea in reply to WileyFrench]

Hi, thanks for your info. I will definitely make arrangements to have regular blood tests and ask for print outs.

[hunter5582]

HU suppresses all hematopoiesis. Platelets, erythrocytes and leukocytes (red and white blood cells) will all be reduced. The usual recommendation when initiating HU is blood tests every two weeks to monitor your response. HU is a toxin so with weak therapeutic effect so dosing is really critical to get right. Max benefit is often achieved by keeping you just below a level of toxicity that is too high. HU works by reducing DNA activity, slowing the action of hemopoietic stem cells - that is the intended benefit. However, it also can break allele strands and inhibit the DNA self-repair function of your cells (all cells). Thus it is a teratogen, mutagen, carcinogen, and is potentially leukemogenic. Since it is a teratogen (birth defects) you must not have a child while on it. Men must wait 1 year post HU and women 6 months to have a child. Women of child bearing years should wear gloves when handling the bottle if not on HU themselves. Sexually active couples are advised to use a condom to protect the partner as HU passes into semen and vaginal secretions. You should have been advised of all of this by your hemo-doc and your pharmacist. This is just a partial list.

Here is more from ePocrates.

Serious Reactions

myelosuppression

leukopenia

anemia

thrombocytopenia

macrocytosis

secondary leukemia (long-term use)

skin carcinoma (long-term use)

infection (peds pts)

vasculitic ulcer

gangrene

dermatomyositis

radiation recall rxn

mucositis, severe

pancreatitis

hepatotoxicity

peripheral neuropathy

fever

hallucinations

seizures

pulmonary fibrosis

renal impairment

tumor lysis syndrome

male infertility

Common Reactions

myelosuppression

stomatitis

infection (peds pts)

anorexia

nausea

vomiting

diarrhea

constipation

rash

skin ulcer

peripheral erythema

facial erythema

nail hyperpigmentation (long-term use)

skin hyperpigmentation (long-term use)

nail atrophy (long-term use)

skin atrophy (long-term use)

scaling

alopecia

renal impairment

ALT, AST elevated

headache

drowsiness

fever

rigors

asthenia

edema

dyspnea

erythrocyte abnormalities.

Hope this helps.

[azaelea in reply to hunter5582]

Thank you very much, Hunter. I always read with interest your very knowledgeable posts and have already learned much from them. I was only given very brief information from the Haematologist when first given Hydroxycarbamide a year ago, mainly about possible skin cancer. I have since done a lot of research and found lots of effects it can have but I must say the list you've provided is very helpful. I wouldn't be told about the pregnancy risks as I am well beyond the childbearing age! I did read about renal impairment and as I've been experiencing pain in my right side (kidney area) mentioned this to Haemo nurse and also my GP ..I am pleased to say he has sent me for a CT scan which I have next week but he says my kidney function is alright from blood test. I will post the outcome on this forum in due course and thank you again for your very informative reply. Regards, Fran

[hunter5582 in reply to azaelea]

I am glad you have found the info helpful. I am aware that HU can benefit some with MPNs, but not all can tolerate it. As one of those who is HU-intolerant, I am rather sensitive to the issues we can face when on this medication. Sometimes our providers are not as informative as we would expect regarding the meds they prescribe. Sometimes they are even dismissive of the adverse effects. With MPNs being so rare, many run into problems as the providers themselves (even hematologists) lack the KSAs to effectively provide individualized care. I hope you are having a different experience. FYI - I never leave my hematologists office without my blood test results. They have their own lab and do them on the spot. All of my providers also have patient portals where I can log in from home and review my current and past results of all of my labs. Should think you would be able to do the same. FYI2 - July to October when on HU sounds like too long of a time span. Would think they would monitor more closely than that. All the best to you.

[Magentas in reply to hunter5582]

Hunter, do you think Jakafi is less risky than HU. All the above looked so frightening, especially as I’m very sensitive to everything.

[hunter5582 in reply to Magentas]

I think the answer to that question can vary based on our unique profile, treatment goals, risk tolerance, and preferences. Jakafi (ruxolitinib) and HU each have a risk/benefit profile that each individual must consider. There is not one right answer for everyone.

As you know, i am HU-intolerant. I experience toxicity even at very low doses. Other people tolerate it for years with no problems. I have tolerated Pegasys quite well. All benefit and no significant adverse effects. Other people cannot tolerate PEG.

If I had to choose between Jakafi of HU, I would choose Jakafi. That is based on my goals, risk tolerance, and preferences. For someone with significant pruritis, Jakafi would clearly be a better choice. That would be the right answer for that person. Many people with MPNs find HU suits them and are fine with that choice.

There is more to the decision than just looking at the adverse effects, although that certainly must be considered. We also have to look at the intended benefit and how the medication works to achieve the desired effect.

Hydroxyurea

Pharmacology .

Metabolism: liver 60%, intestines; CYP450: unknown

Excretion: urine primarily (40% unchanged); Half-life: 2-4h

Subclass: Antimetabolites, Urea Derivatives; Sickle Cell Disease

Mechanism of Action

exact mechanism of action unknown; inhibits ribonucleotide reductase, immediately inhibiting DNA synthesis; increases fetal hemoglobin levels, RBC water content, and sickled cell deformability; alters RBC adhesion to endothelium

Jakafi

Pharmacology .

Metabolism: liver; CYP450: 2C9, 3A4 (primary) substrate; Info: active metabolites

Excretion: urine 74%, feces 22%; Half-life: 3h (parent drug), 5.8h (active metabolites)

Subclass: Immunosuppressants; Kinase Inhibitors, JAK Inhibitors

Mechanism of Action

inhibits janus-associated kinases (JAK) 1 and 2, leading to disruption of cytokine and growth factor signaling pathways

Hydroxyurea is a cytotoxin. It inhibits DNA activity in DNA-active cells like hemopoietic stem cells. It affects DNA activity in other cells too (e.g. endothelial). HU can break allele strands and interferes with the DNA self-repair function. This is how it works and produces its intended benefit. It is effective at slowing down the production of blood cells by interfering with DNA activity in the progenitor cells. It also alters RBC adhesion to the vascular endothelium.

Jakafi is a JAK-Inhibitor. It slows down the activity of the JAK-STAT pathway that is overactivated by the JAK2 mutation. It is more directly focused on what the problem is, particularly when the overproduction of cytokines is an issue. By inhibiting the JAK-STAT pathway, Jakafi also reduces hematopoiesis. The JAK-STAT pathway is quite ubiquitous in what it does. It is involved in various bodily processes. Inhibiting the JAK-STAT pathway can certainly have unwanted effects.

The adverse effects for HU were listed above. here is the list for Jakafi.

Adverse Reactions .

Serious Reactions

thrombocytopenia

anemia

neutropenia

infection, severe

tuberculosis

PML

non-melanoma skin CA

severe myelofibrosis sx exacerbation if abrupt D/C

multiple organ failure if abrupt D/C

respiratory distress if abrupt D/C

DIC if abrupt D/C

hypotension if abrupt D/C

Common Reactions

infection

dizziness

dyspnea

hemorrhage

edema

diarrhea

fatigue

HTN

headache

ecchymosis

musculoskeletal pain

nausea

fever

cough

UTI

thrombosis

weight gain

rash

muscle spasms

anemia

thrombocytopenia

hypercholesterolemia

ALT or AST elevated

GGT incr.

neutropenia

Med facts from ePocrates.com

Note that if all we ever look at is the potential adverse effects then we would not take anything. Not even aspirin or acetaminophen. ALL medications have a risk/benefit profile.

Some MPN Specialists have moved away from the use of HU (including my MPN Specialist). Others continue to use it routinely. Some healthcare formularies prefer HU because it is so much cheaper. Some tend to limit access to other options for older patients since some of the HU risks are associated with long-term use and use by people of childbearing age.

Regardless of what the provider or your healthcare system prefers for whatever reason, you have to decide what you prefer. A good provider will review each of your choices with you,helping you to understand all of your choices. A good provider will respect your right to choose your preferred treatment and assist you in accessing it.

That was a really long answer to a short question. I hope it helps.

[Magentas in reply to hunter5582]

😊 “a really long answer to….”. Indeed and I am very grateful for it! I have a lot more understanding of how to approach my decision. Thank you so much for your time and understanding, Hunter, you really are a godsend.

[Wyebird]

Don’t worry, they will look at all your other blood components.

Ask for / demand a copy of your blood test results.

On the sheet will give your counts

It will have a column stating the normal range.

Another column saying if you are above or below that range.

You can then keep an eye on your bloods and query.

Hope this helps

[azaelea in reply to Wyebird]

Thanks Wyebird, I'm going to ask for a printed copy of my results and ask my GP to authorise monthly blood tests till next Haemo appointment.

[Wyebird in reply to azaelea]

How long betweenappointments?

[azaelea in reply to Wyebird]

3 months, which I feel is a bit long.

[Wyebird in reply to azaelea]

I understand your concerns, your platelets are a good level. Did they offer you a telephone consultation? If not try and get one. So that you could discuss blood results that your GP has authorised. It’s a difficult one to answer. If your heamo is an mpn specialist then I think all you can do is voice your fears.

Do keep me posted.

[EleanorPV in reply to Wyebird]

My experience. My GP authorised me to request a copy of my blood results. He noted this on my patient notes. Even now 3 years later, when I request a copy my receptionist tries to say ‘we can’t do that’. I say please look at my notes.

I do have very nice GP who allows me to also request any blood test whenever I require.

[Wyebird in reply to EleanorPV]

Ouch, maybe a request in writing is needed.

I truly think a copy of your results are useful.

[ChelseaF]

That is what has happened with me, my other counts tanked. I have had tests every two weeks until the last one when they lowered my dose and now I am down to monthly. I think 3 months is a long time if your counts are not yet stable. The plan for me is that when we find a dose that keeps my counts steady we’ll drop to checks every 3 months.

[Anag]

When any such jump happens to me, I run to the next blood test! I went today and mine had jumped from 538 to 909 in 5 weeks!!! I am short of my next TIA. I was able to take immediate precautionary measures. More aspirin, more Anagrelid immediately. I was dizzy, tinnitus, numb hands, hair loss, word loss, fainting. Terrible. Take control of your situation and don’t wait for the docs if you re down so low. Tell them

[Lifam]

My blood test result from GP yesterday showed platelets down to 299, internal organs and other blood cells are fine, I always have a copy of print out from her, I asked for blood test every 2 months just to monitor. My Haem also gives me appointment every 2 months with blood test to keep an eye on everything.