Tutorial on Neutropenia from Dr. Dale

“White blood cells (WBCs) in our body help fight infections. There are various types of WBCs and each has its own way of fighting microbial infections. The most important WBC is called the neutrophil.

“The number of neutrophils in the blood is expressed as absolute neutrophil count (ANC) and it measures the percentage of neutrophils in the differential WBC count. The ANC of a healthy individual falls in the range of 2,500 to 6,000 per microliter.

“A total blood count gives the levels of the three types of blood cells – white blood cells, red blood cells, and platelets. Neutrophils are present in two forms – polys and bands. Polys are also known as segmented neutrophils and are the most abundant of the WBCs. Bands are also called stabs and are immature polys. Both polys and bands destroy invaders (i.e. microbes) in the body.”

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Absolute Neutrophil Count (ANC)

Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study

In a study by C. L. Andersen, et. al, published in the Journal of Internal Medicine, it was revealed that with regard to neutropenia :

1. Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L, may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood.
2. Using a primary care resource, comprising more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nation-wide health registers, risk estimates were assessed.
3. Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality.

The conclusion was that:

The lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively.

In other words, a low ANC cannot be ignored, and requires thorough investigation until the underlying condition causing the low ANC is determined and addressed.

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Clinical Significance of Neutropenia in Routine Complete Blood Cell Counts

Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study

Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L⁻¹, may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood. Neutropenia is associated with viral infections and hematological malignancies in a dose-dependent manner, according to a study published online Jan. 21 in the Journal of Internal Medicine.

C.L. Andersen, from the University of Copenhagen in Denmark, and colleagues examined the clinical significance of neutropenia. A primary care resource was used to examine the correlation with various conditions and all-cause mortality in the four years following neutropenia identification for more than 370,000 individuals.

Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias and myelodysplastic syndromes. Odds ratios [95% confidence interval (CI)] for viral infections were 2.32 (1.84–2.91), 2.80 (2.20–3.57) and 4.77 (3.22–7.07) for subnormal (≥1.5–1.8 G L⁻¹), mild (≥1.0–1.5 G L⁻¹) and moderate–severe (≥0.0–1.0 G L⁻¹) neutropenic individuals, respectively (all P < 0.001). Likewise, odds ratios (95% CI) for haematological malignancies were 3.23 (2.35–4.45), 8.69 (6.58–11.47) and 46.03 (33.98–62.35 ), for the same neutropenia levels, respectively (all P < 0.001). Thus, the lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively.

Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented support focusing attention to viral diseases and haematological malignancies when neutropenia is observed.  “The risk estimates presented here support focusing attention to viral diseases and hematological malignancies when neutropenia is observed,” the authors write.

Read full text of article: http://onlinelibrary.wiley.com/doi/10.1111/joim.12467/abstract

Authors of the study were:  C. L. Andersen, D. Tesfa, V. D. Siersma, H. Sandholdt, H. Hasselbalch, O. W. Bjerrum, P. Felding, B. Lind, Niels de. F. Olivarius andJ. Palmblad^,

Neutropenia Risk Prompts REMS for Antipsychotic Clozapine

The Food and Drug Administration (FDA) has announced changes to prescribing information for the atypical antipsychotic clozapine and a new shared risk evaluation and mitigation strategy (REMS) due to continuing safety concerns and current knowledge regarding the risk of severe neutropenia. Clozapine is indicated for the treatment of resistant schizophrenia and to reduce the risk of recurrent suicidal behavior in schizophrenia and schizoaffective disorders.

The requirements to monitor, prescribe, dispense, and receive clozapine are now incorporated into the new shared Clozapine REMS Program, which replaces the six individual clozapine registries. The REMS program includes all clozapine medicines in order to provide a centralized point of access for prescribers and pharmacists in managing the risk of neutropenia. Starting October 12, 2015, clozapine will be available only through the Clozapine REMS Program.

Important changes to the neutropenia monitoring recommendations and treatment algorithm for clozapine include:

• Absolute neutrophil count (ANC) is the only test result accepted in the Clozapine REMS Program to monitor for neutropenia.
• If the patient is an outpatient, the ANC must be reported to the Clozapine REMS Program before clozapine is dispensed.
• If the patient is an inpatient, the ANC must be reported within 7 days of the most recent blood sample.
• Patients with benign ethnic neutropenia (BEN) can now be treated with clozapine.

This article originally appeared on MPR.

Girl With Rare Blood Disorder Works to Inspire Others

Kara Loader is just like any sixth grade girl. She’s been playing the violin for seven years, loves softball, and says she’s really good at school. She’s a huge Taylor Swift fan, and she has a lot of friends. But something sets Kara apart from her friends and classmates, though it’s nothing you’d be able to see on the outside.

11-year-old Kara has been battling severe congenital neutropenia since birth. Neutropenia is a rare blood disorder, meaning her body doesn’t make enough neutrophils in her white blood cells. So when Kara gets sick, or even gets a cut, her body may not fight off the infection as quickly. 

Kara has to be extra cautious and carry a medical kit with her at school, and when she gets really sick, Kara visits a hematology and oncology specialist at the Cleveland Clinic. She takes a shot of neupogen every day, which helps her build her neutrophils. However, she has to watch how much she takes, because the drug increases the risk of developing leukemia.

Kara has become a bit of a celebrity of her own in the neutropenia community. She said her video inspired a woman in her 30’s to talk about the disorder for the first time .”She always thought that it wasn’t okay, like, it wasn’t normal to tell people that you actually have it. And she said that my video actually gave her the courage to tell it to other people,” Kara said.

Kara said she has one message for anyone else battling neutropenia: “I would tell them everything’s going to be okay.” Kara and her family remain in contact with families they have encountered in the hospitals and at a yearly conference for neutropenia.

Ariana-Leilani also has suffered from neutropenia.   Sign her petition to assure she gets proper treatment and protection from abuse.

Read more: Kara Loader

 

Sepsis: The Uncontrollable Killer

Just hours before he fell ill with sepsis and went to the hospital, and never went home.

Ariana-Leilani has been diagnosed with neutropenia — low immunity causing high risk of infection.   Although she can look perfectly normal, a few hours can mean the difference between life and death.   Neutropenic patients are particularly prone to sepsis, which is the most common killer of Americans.   It is an infection can suddenly turned into the life-threatening condition called septic shock.

Most vexing about sepsis is that doctors can only treat the symptoms. They don’t have an effective treatment for the underlying condition — antibiotics don’t work.

One thing that can help is prompt medical attention — especially when an infection is accompanied with some of the symptoms of sepsis, such as confusion, rapid heartbeat, shaking and skin rash.   In a neutropenic patient, like Ariana-Leilani, GCSF is one of the medicines that can boost the immune system.

Read more: Sepsis, A Wily Killer, Stymies Doctors’ Efforts To Tame It

Please sign Ariana-Leilani’s petition.

A Blood Condition Called Severe Congenital Neutropenia in the UK

Audra Keir (48) and her son, Mark (19), have a blood condition called severe congenital neutropenia which means they lack the type of white blood cells needed to fight bacterial and fungal infections leaving them unable to fight throat, skin and chest infections as well as countless others. Even cuts can see them on a drip in hospital if antibiotics are not taken quickly enough.  A normal cell count for a healthy person is 1500-8000 cells per microlitre of blood with anything under 500 considered a severe case – Audra’s count is often just 20 or 30.

Like Ariana-Leilani, if they are unlucky enough to get an infection and the correct treatment is not given in time then their neutropenia can prove fatal.  “Apart from being very open to bacterial infections, their condition causes extreme fatigue and aching limbs, tiredness, mouth ulcers and, of course, very serious infections which can start off small and become very difficult to treat very quickly as our bodies don’t mount a normal immune response.

As if their illness wasn’t debilitating enough, Audra and Mark have an increased chance of their condition further mutating into acute myeloid leukaemia and when it comes to their treatment, Audra says they face an alarming dilemma.

The Keirs have suffered problems all through their lives due to the neutropenia such as serious infections, long periods of ill health, extreme fatigue and low mood. This, in turn, has led to problems with normal life like education and work with Audra only being able to work part-time in finance and not judged as ill enough to be able to claim any benefits. Mark, meanwhile, was often off school with the condition.

On trying to claim benefits, Audra said, “I feel I was discriminated against at all times through the process because of the rarity of the condition. We are judged as having a disability when it suits and not when it doesn’t and are caught in the middle with no emotional support or otherwise. We do feel very isolated with this condition and I know other sufferers feel the same.

Support for the disease is very limited as Audra explained. “We’ve never had any direct help. We’ve always had to go looking for it. I help run a predominantly Facebook-based support group here in the UK which was started by another lady in Somerset. Our support group has been running for nearly two years and is growing slowly in numbers with 163 members currently.

“Although the group is UK-based, nearly a third of the members come from abroad with people from the USA, Australia and other parts of Europe. We are trying to become a charity. In the USA and Australia they have their own support organisations but there was nothing in the UK.”

The rarity of neutropenia means that the worldwide patient group suffer from public ignorance and even a lack of understanding from medical professionals. Audra’s own consultant haematologist has only ever treated two patients with the condition – Audra and Mark.

In the last couple of years, they have had some support from a specialist genetics support nurse based in Dundee who sees the family at home every few months. Apart from this, they get no support from other official bodies.

With the severity of the Keirs’ condition affecting one in every one to two million people there are only around 60 to 70 people in the whole of the UK with the illness and they don’t enjoy specific experts or centres of medical excellence for advice and support and there is also no funding. Expert advice comes only from contacting an international registry of the disease based in Washington DC, in the US.

Audra said, “Last year I attended a reception for Rare Disease Day at the Scottish Parliament which was highly informative and I hope to do the same this year as the Scottish Government try to push a rare disease UK strategy. I was really encouraged to see that the government is trying to support all sufferers of rare diseases but the strategy is still in its infancy and will take some time to become a reality.”

International Rare Disease Day 2015 takes place on 28th February

Twin Peaks Sheryl Lee, Also Struggles with Neutropenia

Twin Peaks Sheryl Lee, Struggles with Neutropenia

Sheryl Lee rose to fame playing murder victim Laura Palmer in David Lynch’s cult series Twin Peaks. But seven years ago the American actress, now 47, fell victim to a mysterious sickness — neutropenia — that was to plague her for years and make it impossible for her to work.

She had always been very healthy and had a strong immune system, so it was strange that she got a cold and couldn’t easily get rid of it.  Then when she did get rid of it something else would come right back. She kept getting sick for about six months. She couldn’t figure out what was going on.   Her doctor suggested doing some blood tests and immediately discovered that her white blood cell count was low. So then she went through many more tests including bone marrow biopsies until they figured out that she had neutropenia.

After six months of unexplained illness Sheryl, who has an impressive string of film, TV and theatre credits to her name, was diagnosed with neutropenia, a rare blood disorder which makes her much more susceptible to bacterial infections.  As a result of her illness Sheryl says she is still struggling with her health and finances.  From the age of 40, she went through illness for four and a half years. She tried to keep working through it as much as she could but she was physically not able to do as much and if you look sick it’s hard to get a job.

Neutropenia occurs when the bone marrow fails to make enough of a specific type of white blood cells called neutrophils. They are an important part of the body’s immune system and attack bugs that enter the body, particularly bacteria. It usually appears later in life as the result of another condition such as leukaemia, auto-immune disorder lupus, rheumatoid arthritis or infections such as HIV and hepatitis.

It can also result from chemotherapy, a bone marrow transplant or certain medications such as those for an overactive thyroid gland. However it can also sometimes be genetic.   In Sheryl’s case, the cause is something of a mystery. “Nobody knows how I got it. No one in my family that we know of has it,” she explains.   Sheryl, who was treated in a hospital in Los Angeles, had to learn how to give herself injections to stimulate her bone marrow to increase production of neutrophils.    If she developed an infection such as pneumonia she would have to go into hospital and have her medication administered via an intravenous drip. “But being in a hospital is not ideal for someone with a really low immune system so fortunately I was able to get my treatment during the day and then go home and sleep at night.   “But there’s a huge list of side effects, the biggest being intense bone pain. It also causes weakness, nausea and sensitivity to everything – taste, smell, light and sound.  “For years the mental, physical and emotional exhaustion were relentless,” she says. “You face the big questions when you go through that kind of illness. There were definitely times when I didn’t know if I was going to get better. There were a lot of nights spent on my knees in prayer.”

Sheryl, who has a son Elijah, 14, from her brief marriage to Neil Diamond’s eldest son Jesse, searched for her own solutions to her illness, changing everything from where she was living to her diet and cosmetics. She also tried alternative therapies such as acupuncture.   She now lives in a tiny Californian guest house and is taking acting work when she can, recently appearing with Katherine Heigl in Your Right Mind about a country singer fighting for custody of her daughter, which premiered at the Venice Film Festival in August.

“I have to be very aware of how I manage my health. I still have relapses if I push myself too hard and my immune system can’t handle it.”

 

Novartis Now Has Version of Amgen Neupogen Drug

Sandoz announced that its version of Amgen’s NEUPOGEN proved to be highly similar to the original in preventing severe neutropenia in individuals with breast cancer being treated with neoadjuvant myelosuppressive chemotherapy. Neutropenia is a condition where the body has an excessively low number of white blood cells.

The U.S. Food and Drug Administration had accepted Sandoz’s filgrastim application in July, making the company the first to have an accepted filing under the Biologics Price Competition and Innovation Act of 2009.

According to Professor Kimberly Blackwell from the Duke University School of Medicine, biosimilars have the potential to play important roles in widening access to top-quality biologics in the U.S. Since biosimilars are more affordable than the originals they are copying, savings will be generated which can then be used to finance other medical needs.

The biosimilar that Sandoz intends to distribute in the U.S. is already available in over 40 other countries. By the end of the decade, it is expected that biosimilars will account for around a quarter of the $100-billion sales generated by off-patent biological drugs.

Read More: Tech Times

Blood drive to offer support for children with neutropenia

Neutropenia is not a well-known disease and there’s only one network that conducts research for a cure.

‘There’s no awareness month, there’s no ribbon, there’s nothing. It’s just us moms trying to get the story out there and say please can you help us,” said Arnold (the mother of a Neutropenia child)   While most of the people who are diagnosed with neutropenia are young, it’s a disease that can go un-noticed, even by the doctors, or its risks can be ignored.

Luckily Arnold found a doctor who took the condition seriously and, in turn, saved her child from unnecessary risk to its life.   ‘I don’t really want to imagine what it would’ve been like without that diagnosis, because it could’ve been life or death for him.”

A blood drive to offer support for children with neutropenia will be held October 21st Ottumwa, Iowa in honor of Ryder and others affected by the disease.  The Neutro Heroes blood drive and Halloween Bash will be held at the Ottumwa Knights of Columbus hall from four to seven pm next Tuesday, October 21, 2013.

Learn more at KTVO

If you cannot make the blood drive, please sign the petition to help Ariana-Leilani, who also suffers from Severe Chronic Neutropenia.