Deaths related to Nplate?

My 34-year old wife recently died under unexplained circumstances (she is actually a member of this community, although I do not know her username). She had ITP and was on Nplate only for two or so months (perhaps just 6 weeks). All of the doctors (around 20 involved) in the greater Reno area could not figure out what was wrong with her; only that her immune system began to attack her kidneys and lungs. This resulted in respiratory failure and multiple watershed strokes.

The death certificate states: Anoxic Brain Injury, Non Traumatic; Acute Respiratory Failure; Acute Renal Failure, and; Unknown Etiology.

One doctor thinks something may have come from her bone marrow (i.e. an acute form of leukemia) but they were unable to do a biopsy before she passed. She did not have high platelets (got to 150 max and dropped below 100 while in the hospital) so there was no clotting.

My research on Nplate shows no side effects of any kind related to what she went through -- but I was surprised to get a call from the Nplate "company" a few days after her strokes asking questions. My understanding is Nplate increases platelets by increasing production within the bone marrow... and given the doctor thinks whatever auto-immune issue got her came from the marrow as well... And it was very acute.

Does anyone in the community know of any ITP patients on Nplate that died under questionable circumstances shortly after beginning treatment? Any information would be greatly appreciated as I investigate this...

I am sorry for your loss.

I am so sorry and shocked to hear this. 'Shocked' does not even describe it. I have not heard of any deaths related to N-Plate, but I will be looking into it now. It's been considered to be a fairly safe drug.

I looked it up quickly and found this site. I only looked at the first two pages, but it does seem to give some information about N-Plate and serious side effects. I wasn't aware of it.

www.druglib.com/reported-side-effects/nplate/reaction_death/

I would like to try to figure out who your wife was. We are a close community, and we genuinely care about each other. Can you tell me her first name? Maybe we can figure it out.

Again, I'm so sorry for your loss.

I am very sorry for your loss.

After thinking about this, I'm wondering if maybe your wife did have clots. Clotting is very possible with counts over 100, in fact, clots can occur with very low counts. I'm wondering if she had CAPS, or Catastrophic Antiphospholipid Syndrome. It could have caused all of the symptoms that you described (strokes and multi-system organ failure). Antiphospholipid Syndrome is common in people with ITP and although the article below states that most people with CAPS also have Lupus, that is not always the case. This is just a guess; something to consider since you're asking.


The catastrophic antiphospholipid syndrome (CAPS) is a very rare complication encountered in a subset of patients with antiphospholipid antibody syndrome. This rare syndrome is characterized by the development of multiple blood clots that block small blood vessels in several organs in the body. The organs most commonly affected by these small blood clots include the heart, lungs, nervous system, and kidneys. In many ways, this syndrome is similar to another rare disease, thrombotic thrombocytopenic purpura.

Many patients who develop this rare complication have lupus, and infections have been reported to potentially increase a patient's risk to develop the syndrome. Even with the best treatment, as many as half the patients who develop this syndrome do not survive.

Treatment includes anticoagulation (blood thinners), steroids, and a procedure called 'plasma exchange'. Plasma exchange refers to a process whereby a patient's plasma (the liquid part of the blood) is removed and replaced with plasma from blood donors. Patients who survive this life-threatening complication are generally maintained on long-term anticoagulant therapy.
www.apsfa.org/caps.htm


Introduction

Romiplostim (N-Plate) is a thrombopeitin-receptor agonist approved for raising platelet counts in patients with immune thrombocytopenia (ITP). Several hematologic adverse effects have been reported including acute myeloid leukemia, myelofibrosis, and thrombosis.
Methods

We report two cases, one pediatric and one adult patient, who had antiphospholipid antibodies and received romiplostim for ITP. Additionally, we conducted medline, Food and Drug Administration (FDA) Adverse Events reports website, and manufacturer׳s adverse events database.
Results

Both patients developed thrombosis with evidence for catastrophic antiphospholipid syndrome (CAPS) after treatment with romiplostim. No reports or events were found from literature and database searches in regards to thrombosis associated with romiplostim in patients with antiphospholipid syndrome.
Conclusion

These cases illustrate the potential for thrombosis with the administration of romiplostim. The administration of this drug to patients with a history of an autoimmune disease, especially those with positive antiphospholipid antibodies, should be done with caution.

www.semarthritisrheumatism.com/article/S0049-0172%2815%2900196-1/abstract

Requnix,

I am so sorry about your wife.

It sounds to me like what the doctors might be describing is a cytokine storm, where the immune system falls into a sort of feedback loop. My brother died from a cytokine storm after treatment with an experimental drug cured his lung cancer, but overstimulated his immune system, which attacked his own lungs as though they were foreign bodies.

However, I think Sandi's hypothesis of Catastrophic Antiphospholipid Syndrome is more likely accurate, as it is a known (but rare) risk of Nplate. The damage to lungs, brain and kidneys is an excellent fit between your wife's symptoms and CAPS.

Patients with ITP have a higher incidence of antiphospholipid syndrome (APS). 2% of ITP cases are actually secondary to APS. APS reduces platelet counts, so I believe that counts of 150 or even much lower do not at all rule out APS and clotting as the cause of organ failure.

Given the potential for CAPS with Nplate and Promacta, as well as for less catastrophic clotting, I think screening for antiphospholipid antibodies (APA) should be standard procedure prior to treatment, and positive APA should be a contraindication for Promacta and Nplate. Do you know if your wife was screened for APA?

I hope the doctors will search for the cause of your wife's death. It could be an important contribution to medical science.

Sorry to hear about your wife.

First of all, thank you to everyone for your overwhelming support. My wife's name was Colleen.

It's hard to say if APS was a factor; the autopsy revealed no blood clots of any kind, and many x-rays and ultrasounds prior to her passing also revealed no clots. I personally spoke with the doctor who performed the autopsy and she said the results were inconclusive. It's all up to pathology now.

What's interesting is APS was NEVER mentioned by any of the doctors until weeks after she was admitted (and had the strokes, which only took place 4 days after her admittance). And yes, they knew from day 1 she was on Nplate and I made sure her Hematologist was involved...

That page showing all of the Nplate deaths is a bit disturbing, especially given it doesn't show symptoms/signs of what lead up to the death, only that Nplate was involved. The doctors said Colleen was Lupis negative, but a 'trait' came up that could be associated with APS. We'll have to wait and see until all of the pathology comes in.

After reading what's been posted here, it seems to me Nplate could have been the cause, and even worse, what happened to her is "known" but not documented anywhere as to the list of side effects...

I wonder what the APS 'trait' was? APS is diagnosed with any of three antibodies and can be confirmed with a blood test. The clots from CAPS are microscopic and not easy to see. Of course I'm not sure if this occurred, but since it remains undetermined, it's a possibility.

Here is s short video about ITP and clotting.

www.onclive.com/insights/immune-thrombocytopenia/Risk-of-Thrombosis-in-Patients-With-ITP