PH – from patient to researcher

As a research scientist, I’ve always enjoyed my work and taken great pleasure in all aspects of my duties. Jo PickworthI’ve researched various diseases, ranging from detecting water-borne parasites, developing assays for Parkinson’s, Alzheimer’s and Creutzfeldt Jakob diseases, to studying heart disease and currently pulmonary arterial hypertension (PAH). These different areas of research have seen me transition through different environments, starting from small biotech to ‘big pharma’ and more recently to my current position as a research assistant studying for a PhD at the University of Sheffield on the inflammatory interaction with BMPR2 signalling in PAH.

After graduating in biomedical sciences at the University of Bradford, I retained an avid interest in human biology and was keen to undertake a career in research. Having never had a serious illness, I was unsure what disease area to focus on, and to me the patient perspective was an almost abstract concept. This all changed dramatically when I was 37 weeks pregnant and, as a fit and healthy 27-year-old with no personal or family history of illness, I fell seriously ill. Just three days into maternity leave, I was at home when I became extremely light headed and faint. Luckily, I managed to get to the phone to call the maternity ward, and the nurse I spoke to sent an ambulance immediately.

Because I had mixed symptoms of breathlessness, low arterial oxygen levels and evidence of pulmonary embolisms – yet low platelets, bleeding and bruising indicating a lack of clotting – it was a very confusing time for all concerned. It was deemed best to induce labour and carry out the necessary tests following delivery without further risk to the baby. This turned out to be an excellent decision by my consultant as at birth my daughter too was suffering from lack of oxygen owing to the very low oxygen saturation of my circulating blood.

The lack of oxygen caused her to have seizures and a left occipital brain haemorrhage, which had she still been in utero would have been left untreated and therefore far more devastating. During labour I lost a lot of blood and needed several transfusions. Having got through the labour, feeling battered and extremely tired, I started to be put through the investigations into what was causing my symptoms. My condition was peculiar as the onset seemed so sudden, but it had clearly been developing for some time, given the extent of the clotting in the lungs. Looking back, however, I now realise that I did in fact show the non-specific symptoms that included shortness of breath, light-headedness, back and leg pain, and indeed I visited my GP and midwife complaining of several, if not all, of the symptoms. Many of these were unfortunately masked by the apparently ‘normal’ symptoms of pregnancy and my inexperience at picking them up. Following a long stay in the HDU and extensive testing, I was diagnosed with extensive bilateral pulmonary emboli (PE) and right atrial thrombus further complicated by HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome pre-eclampsia. A concurrent diagnosis by echocardiogram of pulmonary hypertension and a clot in the pulmonary artery was noted.

I was placed on warfarin for six months to disperse the clots, in the hope that my pulmonary arterial pressures would return to normal. During these months I tried (and failed) to fight the urge to research my potential illness but, as I’m sure is the case with most people given such a diagnosis, I faced an irrepressible urge to find out my prognosis. I talked at length with health visitors and my (many) doctors, as well as doing my own online searches. I spent the following six months in limbo knowing that I potentially had a degenerative disease but trying remain positive while waiting for the clots to clear and for a followup echocardiogram to confirm a solid diagnosis.

Even with my scientific background, I sometimes struggled to take in what I was being told in hospital – particularly when it related to my daughter, as panic took over. I also became acutely aware that the whole experience was easier for me than for those around me. I knew how I felt, but my family could only guess at that from how I looked. I found I could handle information surrounding the possible long-term implications of my diagnosis and yet, understandably, my family struggled to cope with my change in circumstances.

It was far more difficult for me to deal with the information surrounding my daughter’s condition and with my feelings of guilt and responsibility, since it had been my lack of oxygen that had caused her illness. I asked myself why I hadn’t noticed my symptoms earlier, and whether maybe all this could have been avoided.

Though irrational, these thoughts must enter the heads of all patients and, while none of it was my fault, I did and still do feel responsible for having caused my daughter’s problems at birth, although thankfully there was no lasting damage.

I was lucky that many of my husband’s family are medics, which really helped him to deal with the events and information overload of those first few weeks in hospital. With his wife and newborn daughter in separate high dependency units, it must have terrifying and unimaginable. I know it helped him to talk things through with his family.

Fortunately after six months’ treatment with warfarin my clots dispersed and, with them, the pulmonary hypertension. A later diagnosis of a silent thrombophilia known as antiphospholipid syndrome (APS) was given, although it is still unclear what caused me to develop this autoimmune disease. After hearing that diagnosis, I realised that I had shown symptoms, including suffering from temporary losses of vision, for years. In the months following my illness, it was made clear to me that, should the PH persist, the high risks involved meant that further pregnancies would be out of the question. However, once it became obvious that the PH had been linked to the PEs and that this condition was caused by APS, I was offered counselling on the possibility of having more children. It was thought that, with careful monitoring and prophylactic daily injections of clexane throughout pregnancy and for six weeks post delivery, the risk of recurrence would be low.

Nevertheless, despite daily injections of low molecular weight heparin, I suffered from further PEs in the weeks following the birth of my second child, so I’m now on lifelong prophylactic daily warfarin tablets. I’m under strict medical instruction to avoid any further pregnancies and, not wanting to push my luck any further, I’m happy to follow that advice.

These experiences did give me an insight into what patients with pulmonary hypertension go through: all those hospital visits, tests, procedures, the emergency care and lifelong treatments, not to mention all the worries thatare perfectly normal under such conditions. Having been so ill without realising it, I now struggle to trust my own judgement about how I feel. I find myself wondering if every little pain is another clot, and I’ve had to learn again how much breathlessness is normal when going for a run. I lost my nerve to know how far I could go, what’s normal and what’s not.

For me, this has been one of the hardest things to overcome – experiencing symptoms so similar to those I felt when ill makes it difficult to keep pushing myself and accept things as normal, and to try not to feel scared. While I have had an amazingly positive outcome – in large part due to the vigilance and dedication of my obstetric consultant and the fantastic treatment I received under her care – I know that it could easily have been far more serious!

This gives me a huge incentive to do what I can to help drive research that could advance treatments for other patients with PH. By chance, eighteen months after By chance, eighteen months after the birth of my daughter I was offered the opportunity to work in PAH research with Novartis Pharmaceuticals (Horsham).

After my second child was born (a son), I moved north and was offered a research position in the Department of Cardiovascular at the University of Sheffield. This has close links with the Sheffield Pulmonary Vascular Disease Unit, the largest of the seven national specialist centres for the treatment of pulmonary hypertension. I jumped at this opportunity as, from the patient’s perspective, I’m so aware how important research is. I found I had increased vigour and a real incentive to make every experiment count, as well as to learn as much as I can from interactions with medical professionals. On the flip side, I also know that one of the biggest constraints on moving research forward is the lack of availability of patient samples. As a patient, I’m always happy to donate samples for research purposes and, as a researcher, I’m always incredibly grateful when another patient donates samples. Every single patient sample donated can really make a big difference to enhancing our understanding of this disease.

I thoroughly enjoy my work and feel a sense of satisfaction with what I do, so I’m thrilled whenever small inroads are made into the understanding of the disease and am even more delighted when I feel that I have played a small part in those breakthroughs. I am enthralled at conferences when I hear about all the research that is going on into this disease. And, although sometimes the descriptions can be a little scary, I enjoy the fact that there’s such a wealth of research going into improving the quality of life for PH patients. I’m sure it’s difficult for most researchers to imagine this disease from a patient’s perspective and, while early research breakthroughs are still a long way from finding a ‘cure’, I for one take satisfaction in the fact that each one, big or small, is taking us a step closer.

My research now is focused on several projects, including investigating the links between inflammatory signalling and BMPR2, helping to develop novel human antibodies for pre-clinical and clinical trials and investigating putative serum biomarkers for PH. The research group interlinks well with the clinical service and runs a biobank funded by the British Heart Foundation, recruiting patient blood samples at diagnoses. These critical and valuable samples are used for a variety of studies, on which the group is collaborating with a number of other research centres in the UK, Europe and the USA.

Jo Pickworth
Research Assistant
Department of Cardiovascular Science.
www.phassociation.uk.com