If an effective medicine is available to treat a disease, is it a human right to access it? What if the cost is very high? Pharmaceutical companies who dedicate resources to research and develop cures need to recoup their investments in order to continue pushing for solutions. Governments need to make hard choices on where to spend public resources. Disease management protocols are complex. Right now, for the approximately 20 patients diagnosed with Paroxysmal Nocturnal Haemoglobinuria (PNH) in New Zealand, the high costs to provide the available medicine have been determined to outweigh the benefits. From an economic perspective, the logic is clear. From a patient’s perspective—my perspective—it is harder to reconcile.

My journey started with a serious ski accident in January last year in Grenoble, France, which left me broken and requiring multiple surgeries on both my femurs and pelvis. As a team of incredible doctors raced to stem bleeding and stabilise me, I was given blood transfusions to replace the significant blood loss I experienced. In the aftermath of the operations, I fell into a coma, suspended between life and death for a month as my body protected itself from the intense pain and trauma. I was on a ventilator and required regular blood transfusions to boost a precarious blood count. Doctors were already suspecting an underlying issue with my blood, noting continued thrombocytopenia. My parents flagged that I had just started seeing a GP at university because of some unusual bruising that had started to appear sometimes, and that I had been prescribed iron supplements while they monitored the situation. Given the acute state of my health, my blood was a secondary consideration at this stage—something to look into at a later point. I survived, came out of the long coma, and then started an intense 8-month period of grueling rehabilitation in a neurorehabilitation centre. My blood count remained unsteady and was regularly monitored. A bone biopsy was undertaken. I had so much to deal with, and my doctors advised me to take things one step at a time as we figured out what was happening.

Just as I began to reclaim the fragments of my life and plan my return to studies at the University of Auckland (where ironically I was pursuing a career in biomedicine), I was hit with the shattering diagnosis of a rare blood disorder: PNH. The biopsy of my bone marrow showed that I was not producing blood normally and PNH clones were present. Of course, the first thing I wanted to know is whether it is curable. No. Is there a treatment available to help manage it? Yes. Relief washed over me. But when the doctors explained how serious PNH is, it was a daunting prospect, and I realized I would be dependent on the medications for the rest of my life to continue living. When you are 21, with dreams and hopes, your whole life ahead of you, it’s a heck of a reality check.

The next blow was being advised to remain in Europe so that I could access PNH treatment. I was told the medication isn’t yet available in New Zealand and that if PNH is untreated it can be life threatening, causing thrombosis. I was devastated. How could it not be available? I love New Zealand. I was living my best life studying at university - and all my friends and extended family are there! The life I was building has been totally interrupted. My future is uncertain.  On one hand, I am grateful that I have been diagnosed, that I have access to medicine in Europe, and that science continues to evolve and progress. I hope this article contributes to efforts in raising awareness and interest in the wider scientific community, to advocate for more attention and investment so we can unlock more accessible preventative and curative options to support a growing number of PNH patients.

What is Paroxysmal Nocturnal Haemoglobinuria (PNH)? 

PNH is a rare acquired bone marrow failure disease. Bone marrow is the organ that produces blood cells, so PNH is classified as a haematological disorder. In plain English, it can be broken down to; “Paroxysmal”, meaning sudden or episodic; “Nocturnal”, referring to its occurrence at night; and “Haemoglobinuria”, which describes the presence of haemoglobin in the urine. It is characterised by the destruction of erythrocytes, a process also known as haemolysis [1].

The root cause of PNH comes from a deficiency in haematopoietic stem cells (HPSCs) in bone marrow, which serve as the source for all blood and immune cells (erythrocytes, platelets, and white blood cells). These HPSCs normally replicate to create new healthy blood cells, however sometimes they can divide and produce PNH affected stem cells instead. When these PNH affected stem cells divide, they in turn produce more defective blood cells, called PNH clones [2].

Interestingly, everyone has a small percentage of PNH clones, ranging from 1–100% of blood cells, but few have enough clones for it to be routinely detected. Expansion of these clones results in a clinical detection of PNH [3].

Genetic Basis of PNH 

PNH is acquired, so it is not a genetic disease and cannot be passed on. It is typically diagnosed in young adults and arises due to a somatic mutation in PIG-A (X-linked phosphatidylinositol glycan class A), which encodes the synthesis of GPI-anchored protective proteins. Of these proteins, CD55 and CD59 play a critical role in regulating the complement part of the innate immune system, preventing excessive cell destruction [3].

In PNH, the HPSCs carrying the PIG-A mutation clonally expand, giving rise to more blood cells that lack GPI-anchored proteins. Without CD55 and CD59, cells are unprotected by complement-mediated lysis, leading to the premature destruction of erythrocytes, a process called haemolysis [4]. Lactate Dehydrogenase (LDH) is an enzyme found in red blood cells and is an important indicator of the extent of haemolysis in the patient. Monitoring LDH levels are key to tracking disease progression and response to treatment therapies.

Researchers still do not know what triggers the PIG-A gene to mutate, but it is an ongoing area of research. One prevailing theory is that of immune escape, which suggests that the HPSCs with the PIG-A mutation gain a selective survival advantage in the event of immune-mediated bone marrow injury [5]. In such autoimmune scenarios, normal stem cells are destroyed, while the mutated PNH clones–lacking the surface protective proteins– are able to escape immune detection. Over time, these resistant clones proliferate and dominate the bone marrow, giving rise to the clinical features of PNH. The theory is compelling and explains the strong association with aplastic anaemia, where there is an altered immune environment. It may also help with the explanation of why PNH is most commonly diagnosed in young adults rather than in childhood.

Symptoms and Complications of PNH 

Symptoms of PNH can vary widely among patients, with haemolysis as the primary clinical hallmark. The lack of GPI-anchored proteins leads to uncontrolled activation of the complement system, resulting in severe intravascular haemolysis. The rupture of erythrocytes releases haemoglobin, subsequently excreted by the body through the urine, resulting in dark, coca-cola-coloured urine [1, 3]. While haemolysis is ongoing throughout the day, it worsens at night because the urine becomes more concentrated during sleep.

Other PNH symptoms include fatigue and weakness. The breakdown of erythrocytes releases haemoglobin, the protein responsible for oxygen delivery to body tissue. As a result, the oxygen-carrying capacity of the body is reduced, and the body tissue receives insufficient oxygen, leading to extreme fatigue [5]. The free haemoglobin in the bloodstream is usually bound to haptoglobin, a blood serum protein released by the liver that helps clear away free haemoglobin after cell death [6]. With PNH however, the continuous destruction of erythrocytes overwhelms the available haptoglobin, leading to an excess of free haemoglobin in circulation, which can cause kidney damage and haemoglobinuria.  

PNH patients may also experience difficulty breathing, frequent headaches, erectile dysfunction, and abdominal pains, which further impact daily life and overall well-being [5].

It can often take many years for patients to be diagnosed with PNH. On average, research shows it can take up to five years or more for a diagnosis [7]. In my case, because of my accident, my diagnosis was fast-tracked. A silver lining of sorts, but an important one, given that when untreated, PNH is a life-threatening disease.

 PNH and Bone Marrow Failure 

PNH has a strong link to other bone marrow failure diseases such as aplastic anaemia (AA) —as in my case—illustrating the disease’s wider implications. The bruising I was noticing was an early sign of thrombocytopenia. AA is a severe bone marrow failure disease, characterised by T cell-mediated autoimmune destruction of HPSCs. Notably, having AA is the only known risk factor for developing PNH.  

PNH-related bone marrow failure manifests in multiple ways:

• platelet deficiency (thrombocytopenia), leading to easy bruising and excessive bleeding
• erythrocyte deficiency (anaemia), leading to fatigue, pallor, and weakness
• white blood cell deficiency (leukopenia), weakening the immune system leading to increased susceptibility to infections

Ironically, having a bone marrow failure that results in a low blood count can mask or delay the development of PNH. When you don’t have enough blood cells racing around your body, there will be a lower incidence of mutant cells. Once the blood count improves, the bone marrow produces more blood cells, both healthy and those originating from PNH clones. The clones may increase, simply because there are more precursor cells available for the PNH mutation to expand within.

Treatment Options 

Despite the life-altering nature of PNH, there is hope on the horizon. Targeted therapies, particularly complement inhibitors, have revolutionized PNH management globally. Inhibitors like eculizumab and ravulizumab help by preventing the immune system from attacking red blood cells prematurely [8]. The treatments work by binding to the C5 complement protein and obstructing it, preventing the formation of the membrane attack complex (MAC)—a key driver of haemolysis.

I am thankful treatments have been developed and are available to manage PNH. While these treatments drastically improve survival rates and quality of life, they come at a steep cost [9]. In over 40 countries—including Australia, Italy, and the Netherlands— they are publicly funded. Devastatingly, it is not publicly available in New Zealand primarily because of the high price being sought by the pharmaceutical company Alexion [10].

In addition, supportive care helps alleviate PNH-related symptoms and complications. Supplemental iron therapy, blood transfusions, and erythropoietin (hormones secreted by the kidneys to stimulate red blood cell production) can help patients suffering from anaemia [10]. However, the only curative treatment for PNH is a bone marrow transplant. Due to its significant risks and high mortality rates, it is reserved for patients with severe aplastic anaemia [11].

A call for action: Advancing PNH Care and Advocacy 

The growing recognition of the severity of PNH is prompting both governmental and private sectors to allocate more resources towards effective treatment options, research investment, and clinical trials. As a result, we are expecting a rising demand for these therapies in the market. Advancements in biologics are actively shaping the rapidly evolving PNH therapeutic landscape, with monoclonal antibodies and complement inhibitors aiming to block the immune system’s attack on red blood cells [10].

However, treatment breakthroughs are meaningless if patients cannot access them. The disparity in global treatment availability underscores the need for increased awareness, policy reform, and investment in both treatment accessibility and research. Advocacy efforts should focus on fostering a sense of collaboration between clinicians, scientists, and policy makers to ensure that no patient is left behind in the fight against this rare and devastating disease [11]. After much reflection, I decided to share my personal story to put a face to the numbers—to show that behind every rare disease is a real life, a real struggle, and a real voice. As a patient and student affected by this disease, I urge the medical and scientific community to prioritize discussions on pharmacoeconomics, ethical treatment allocation, and innovative solutions that balance economic sustainability with humanitarian responsibility. By pushing for progress, we can create a future where PNH patients have access to the care they need.