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Improving the care of haematology patients during COVID-19. Dr Philip Murphy Blood Cancer Network Ireland
VTE is recognised as being a leading cause of cardiovascular mortality worldwide. Dr Barry Kevane Mater Misericordiae University Hospital & Ireland East Hospital Group
Gene therapy for haemophilia has been on the horizon for over 20 years. It is now close to becoming a licenced therapy. Brian O’Mahony Chief Executive, Irish Haemophilia Society
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IN THIS ISSUE
04 Hopeful future for multiple myeloma patients
05 Why I chose blood thinners over surgery for DVT
06 How to prevent a leading cause of cardiovascular mortality Business Development Manager: Ross Bannatyne Email: ross.bannatyne@mediaplanet.com Content and Production Manager: Kate Jarvis Managing Director: Alex Williams Head of Business Development: Ellie McGregor Digital Manager: Jenny Hyndman Designer: Thomas Kent Content and Social Editor: Harvey O’Donnell Paid Media Strategist: Ella Wiseman Mediaplanet contact information: Phone: +353 1 691 8842 E-mail: uk.info@ mediaplanet.com All images supplied by Gettyimages, unless otherwise specified
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Improving the care of haematology patients during COVID-19
The pandemic has had a dramatic effect on the lives of people worldwide, but we must adapt and continue the vital work we are doing in the blood health sector.
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atients with blood cancers would be expected to be at increased risk of severe sequelae from COVID-19 infection due to their age profile, their underlying condition and their treatment. Thus, Irish healthcare professionals have had to take unprecedented steps to protect patients with blood cancers from the effects of infection by COVID-19. Many patients are being monitored remotely by phone or video consultation to reduce risk of exposure. Decisions about whether to proceed with strongly immunosuppressive therapy or to delay treatment with careful monitoring have been carefully made. Each individual case is carefully considered, using a multidisciplinary approach, national and international guidelines and taking into account experience from other countries. Testing for white blood cell abnormalities in COVID-19 patients The unsung heroes in the fight against COVID-19 are our hospital laboratory staff. Despite the stressful circumstances, the hospital laboratory staff continue to perform the molecular testing for COVID-19, provide excellent 24-hour laboratory cover, generate rapid blood test results and provide blood products for COVID-19 patients with severe bleeding problems. In my laboratory, white blood cell abnormalities distinctive to COVID-19 infection can be detected by
microscopy in about 70% of COVID-19 positive patients and may aid in the early detection of this viral infection. Hope for chemotherapy-resistant patients, despite COVID-19 Myeloma is a cancer of plasma cells in the bone marrow, which usually presents with severe bone and/or kidney disease. This year, we have seen patients with advanced, chemotherapyresistant myeloma, enter complete remission using an oral therapy targeting BCL2 protein. Targeting BCL2 and similar proteins offers great hope for many other patients with blood cancers in the future. Hodgkin lymphoma is a cancer of lymph nodes with a generally excellent response to combination chemotherapy. However, a minority of patients are resistant. An ongoing study is researching using a combination of chemotherapy and an antibody-drug conjugate as initial therapy for Hodgkin lymphoma. This study is a BCNI and the European Organisation for Research and Treatment of Cancer (EORTC) collaboration. There is an antibody-drug conjugate that specifically targets the Hodgkin cancer cell and its combination with chemotherapy promises to improve the prognosis of this lymphoma even further. Blood conditions must not be overlooked Haemophilia is a hereditary disorder affecting males, who are at risk of
Dr Philip Murphy Head of Haematology Department, Beaumont Hospital and Director of Clinical Trials, Blood Cancer Network Ireland
severe bleeding due to low levels of clotting factors. Traditional treatment includes replacement of the missing clotting factor by intravenous infusion. However, in the recent past, gene therapy offers the hope of long-term cure for such patients. In a ground-breaking development, three Irish patients with haemophilia B have entered an international clinical trial, which uses a viral vector to deliver gene therapy. The first Irish patient received the gene therapy in March of this year. Based on earlier studies, it is expected that the effects of a single gene therapy may last for many years or even a lifetime. Women may overlook symptoms of bleeding disorders Heavy periods or heavy menstrual bleeding (HMB) affect many women and, in one fifth of cases, may be due to an underlying bleeding disorder. With early diagnosis, HMB may be effectively treated, significantly improving quality of life. Recognition of bleeding disorders is essential to reduce the risk of future bleeding at operations or childbirth. A new Health Research Board funded public awareness campaign “Know Your Flow” (www.knowyourflow.ie), which was launched this year, seeking to educate women about heavy periods and their impact as well as signs of an underlying bleeding disorder.
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Blood clots treatable if caught in time but fatal if ignored 60% of blood clots happen as a result of a hospital stay and many are preventable. Thrombosis Ireland & HSE have rolled out one million Blood Clot Alert Cards to all the Irish Public Acute Hospitals with the recommendation that they be used as part of their hospital VTE (venous thromboembolism) prevention strategy. All patients admitted should receive this card before discharge as their risk of getting a blood clot remains high for 90 days after they go home.
Ann Marie O’Neill Patient/Founder & CEO Thrombosis Ireland
What is a blood clot? A blood clot is made up of platelets and red blood cells that form a plug and a mesh of cross-linked fibrin protein, causing a blockage in a blood vessel. Blood clots do not discriminate between young, old, male or female. They can happen to anyone. They are very treatable if caught in time but can be potentially fatal if ignored or missed, so awareness can be lifesaving. What increases your risk of getting a blood clot? • A hospital stay – and the following 90 days once you’re home. • Having active cancer or receiving cancer treatment. • Being pregnant or having had a baby fewer than six weeks ago • Becoming immobile (more than three days in bed/travel non-stop more than six hours/ in a leg cast Risk may increase further if: • You or a close relative had a blood clot • You had surgery in the last 90 days • You have thrombophilia (tendency to clot) • You are on the oral contraceptive
pill or HRT • You have heart, lung or inflammatory disease • You are over 60 years of age or are overweight • You have varicose veins that become red and sore Signs and symptoms of a blood clot • Swelling or pain in one leg, usually the calf, or arm • warmth or redness in the leg or arm • Shortness of breath or rapid breathing • Chest pain (particularly when breathing deeply) • Coughing or coughing up blood If you have one or more of these symptoms, you may have a clot and need urgent treatment. Do not delay seeking medical advice. Blood clots are preventable in many cases and very treatable if caught on time. Patients and carers need to be aware of the risks and the signs of a blood clot, in order to protect themselves and their loved ones, particularly in the 90 days after discharge from hospital.
Blood clot alert card The blood clot alert card is designed to be used as an information tool for patients admitted to our acute hospitals. It informs patients of their risk, the signs and the need to get medical attention fast. It also prompts them to request a VTE risk assessment from their doctor to assess if they need intervention to prevent blood clots while in hospital and when they go home. It reminds them of the importance of walking and moving as much as possible to keep their blood flowing and the need to keep hydrated. Awareness about blood clots will save lives. Patients are entitled to be informed so they can be vigilant and proactive about their health. The card itself is laminated and folds to fit in your wallet.
For further information or support please contact Thrombosis Ireland on 087 3634828 or go to our website www.thrombosisireland.ie
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New treatments improving survival and quality of life for multiple myeloma patients
Hopeful future for multiple myeloma patients Encouraging results from CAR-T therapy trials bring hope for those with relapsed and refractory multiple myeloma.
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esults from the first significant trials into CAR-T therapy for multiple myeloma, a bone marrow cancer, were published last year and offer fresh promise for patients who have few other options. Patients who participated in the trials, including a few from Ireland, all had an advanced stage of the disease, and had already undergone multiple other treatment cycles. “We’re aware of patients getting very good responses, but unfortunately, those are not sustained beyond six to 12 months,” explains Professor Paul Browne, Professor of Haematology at Trinity College Dublin. Waiting for mature results, but it’s a positive start The second generation of trials addressing issues of durability are ongoing. These studies are also assessing whether outcomes could be improved by bringing CAR-T therapy forward in a patient’s myeloma experience, rather than waiting until they are at an advanced stage. “In principal, that sounds like an appealing idea, but we’re going to have to wait for mature results,” continues Browne. Initial signs are promising but,
Professor Paul Browne Professor of Haematology, Trinity College Dublin and St James’s Hospital Written by Kate Sharma
realistically, it will be years rather than months before there is any talk of mass roll out and licencing. It’s worth remembering though that, as research gathers momentum, more patients will have the opportunity to access the therapy through trials. Browne is hopeful that some may even be conducted in Ireland. Infrastructure and funding are already in place to start treating patients who have other forms of blood cancer with CAR-T therapy in the country in the
We have a very good track record of delivering stem cell therapy. We have a very attractive system with an integrated approach working with partners, and some seed funding.” very near future. While great leaps have been made in advancing CAR-T therapy to treat multiple myeloma, it takes significant time to accumulate the evidence needed to progress further. The journey continues, but it does so with great hope.
Multiple myeloma is the second most common blood cancer in Ireland and is diagnosed in approximately 250 patients per year in this country. The disease can be detected incidentally when an abnormal protein is found in the blood or urine, or the patient can experience symptoms, which raise the alarm that something is wrong.
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Siobhan Glavey Consultant Haematologist, Beaumont And Connolly Hospitals
orldwide in 2020, recent years with the aim of delivering patients with multiple a more personalised approach to myeloma are benefitting treating this disease in individual from the many new patients. treatments that have become available One such test is “minimal residual for this disease over the last 15 years. disease” (MRD), which has emerged This is translating into a better from several international clinical quality of life on treatment and longer studies as an important predictor survival for patients in Ireland. of remission times and survival in Earlier detection, due to greater multiple myeloma. This test may also awareness of the disease and more help doctors to decide which patients sensitive tests, has also led to might benefit from certain types improvements for patients. However, of treatment, particularly when this cancer typically combined with follows a remitting genetic tests and relapsing of cancer cells. course, which means We hope that, in future, At Beaumont that patients need Hospital and Royal this will lead to a more close monitoring College of Surgeons personalised approach in Ireland (RCSI), in and new treatments to the treatment to be available to collaboration with them when the several hospitals of this disease for disease re-emerges throughout Ireland, Irish patients. in their blood or via the Blood Cancer bone marrow. Network Ireland and Cancer Trials Ireland, we are carrying Aiming to personalise approach to out a research study looking at treatment combination of MRD and genetic tests Predicting when the disease might to try to identify how patients will re-emerge and what treatment is best respond to treatment, and learn more suited to a particular patient is one about predicting prognosis. of the biggest challenges we face in We hope that, in future, this will treating this disease. lead to a more personalised approach Along with new treatments, to the treatment of this disease for advanced testing techniques have Irish patients. also been developed worldwide in
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Why I chose blood thinners over surgery for DVT Blood thinners were the only route I would consider after my harrowing experience with, what should have been, a fairly straightforward medical procedure.
Joanne Campbell Patient
The catheter that should have improved my chemo experience In December, I started chemotherapy. Because of the risk of lymphoedema the only arm available for me to have the infusions was my left arm. The oncology nurses wanted to insert a picc (peripherally inserted central catheter) line to avoid the hassle of looking for veins every week and also the chemotherapy is meant to be quite hard on veins. So, I had a picc inserted in my arm in early December. During the insertion of the picc, the nurse flushed it and I could hear water in my ear! She double checked what she had done and then sent me for an X-ray to check it. In the X-ray they noticed it had twisted at the tip, so they told me to come back the next morning to have it redone by a doctor. My neck pain and palpitations were put down to anxiety That night I felt sore around my neck area and I had palpitations during the night. When I went the next day the doctor looked at it under X-ray and said it had rectified itself. Over the following days I complained about neck pain but was told it was probably anxiety, or the way I was holding myself; maybe being nervous about having it in. The doctor said I had no nerves in my vein so it couldn’t hurt. The nurse suggested using a pain relief cream on my neck. My first chemo followed so I wasn’t feeling great and, at this stage my neck was still sore but so was my underarm. I complained again but again was told that picc lines can be a bit annoying. The following day I could hardly lift my arm in the shower to wash my hair and when I got out I noticed my forearms were different colours, I knew something was wrong so I drove to the hospital. I’d developed a deep vein thrombosis the size of the catheter It was there they looked and noticed
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n September last year, I was diagnosed with breast cancer. At the time I had to take sick leave from my full-time job as professional violinist to have treatment. I had my first surgery at the start of October and then I had a further surgery at the end of the same month. The second surgery involved a mastectomy and taking lymph nodes from my right arm, which was a concern to me as I could develop lymphoedema and it could affect my career.
my upper arm was slightly swollen, I was sent for an ultrasound and they discovered I had developed a deep vein thrombosis (DVT) the full length of the picc. It ran from my elbow up into my jugular and to my heart. The oncology team consulted with the vascular team in Dublin and they then removed the picc line. I was injected with heparin and sent to Dublin where I spent eight hours in A&E waiting to see the vascular team. A doctor from the team came down to see me before I was admitted, and I mentioned that I needed that arm to work and she replied: ‘You’ll not play the violin again!’ When I was admitted, a heparin drip was put in my foot and my arm was wrapped and put in a sling. The doctors decided that they would like to try to remove the DVT as it was relatively new but, after consideration, I decided not to do the procedure. The side effects of bleeds and a stroke just seemed too frightening, as I was still more concerned about surviving the cancer. I felt I didn’t need any more risks. I checked with my oncologist that I would I still be able to use that arm for my chemotherapy and, when he said yes, I was happy to go down the route of blood thinners. My aftercare was limited, at best I left hospital just before Christmas with an antithrombotic prescription and a couple of elasticated bandages for my arm. That was the full extent of my care. After a week, a vascular doctor rang and told me she would send me a prescription for a compression sleeve. One of the oncology nurses referred me to a hospital physio and six weeks later I got a sleeve. I attended the physio for exercises for both arms and she was helpful, but the symptoms were still there. I stopped wearing the sleeve as it was making my hand swell and my neck sore. I continued to have chemotherapy throughout this time through whatever vein in my arm the oncology
During the insertion of the picc, the nurse flushed it and I could hear water in my ear! nurses could find. Sometimes finding a vein took over an hour. I just want more clarity and better communication At my vascular follow up appointment, three months later, I brought a list of questions to which I got no answers. I wanted to know about flying, playing the violin, exercises, anything to improve the symptoms but the doctor didn’t answer any of them. In fact, he googled the answer to my flying question. I told him my oncology team had thought I would stay on my prescription until the chemo was over, so he wrote me a prescription for another three months. I assumed they would do another ultrasound but no, he signed me off saying ‘too many cooks spoil the broth’. That evening, he rang me and said he had seen a letter from my oncologist saying that my team would be guided by him as to when I should come off the antithrombotics. So, he changed his mind, told me to finish up my old prescription in a week and not to use the new prescription. That meant I finished the antithrombotics five weeks before the chemotherapy ended. Since all this has happened, I have had intermittent pain and heaviness in my arm and swelling in my hand. I’m concerned I may never be able to return to full time playing again. I’m unsure as to when I can fly again. I don’t know what exercise is safe, whether weight bearing exercise is a good or bad idea, really, I’ve had next to nothing in follow up care.
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Dream therapy almost reality for haemophilia The long-cherished hope of seeing gene therapy and a possible functional cure for haemophilia is now visible on the horizon.
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person with haemophilia B has a deficiency in coagulation Factor IX. In normal individuals without haemophilia, the Factor IX level is typically between 50% and 150%. In severe haemophilia, it is usually less than 1%. Gene therapy involves an intravenous infusion of a modified human Factor IX gene, carried within an attenuated virus known as an adeno associated virus (AAV). This delivery system is known as a vector. AAV virus does not cause illness. In this case it is acting as a delivery system for the FIX gene. The vector travels to the liver where the FIX gene is released, and these liver cells then start producing factor IX.
How to prevent a leading cause of cardiovascular mortality
Brian O’Mahony Chief Executive, Irish Haemophilia Society
Hospital-acquired venous thromboembolism (HA-VTE) is the leading cause of preventable hospital deaths.
haemophilia or even normal. It is also our hope that people with haemophilia in Ireland will have an opportunity to participate in Factor VIII Gene Therapy clinical trials (for haemophilia A) in 2021.
Venous thromboembolism: Acute and chronic morbidity & mortality Venous thromboembolism (VTE), which comprises primarily of pulmonary embolism (PE) and deep vein thrombosis (DVT), has an annual incidence of approximately one in 1,000. VTE is recognised as being a leading cause of cardiovascular mortality worldwide. Among survivors, a substantial burden of chronic morbidity has been reported. Well-known chronic complications of VTE include a potentially life-threatening pulmonary vascular disease called chronic thromboembolic pulmonary hypertension, and post-thrombotic syndrome; a disorder characterised by chronic pain, swelling and ulceration of limbs affected by deep vein thrombosis. Recent data pertaining to a range of other newly described ‘post-PE’ syndromes has also been reported, suggesting that a substantial burden of chronic morbidity associated with this condition exists, which has likely been under-appreciated until recently. This chronic morbidity associated with VTE is a major contributor to healthcare resource utilisation globally as well as a major negative influence on patient quality of life.
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Gene therapy could be licenced in the near future Gene therapy for haemophilia has been on the horizon for over 20 years. It is now close to becoming a licenced therapy. It is anticipated that the first Factor VIII gene therapy will be licenced later this year and the first Factor IX gene therapy will be licenced in 2021. When licenced, these therapies will initially be options only for adults with severe haemophilia. (As the liver in a child continues to develop, there Three individuals undergoing is significant turnover of liver cells so clinical trials the current gene therapies in clinical On World Haemophilia Day in trials would not be suitable for April 2019, the children as the liver Irish Haemophilia cells producing the Society highlighted factor would be lost the fact that clinical as the child’s liver Gene therapy for trials of gene cells changed). haemophilia has been therapy for both on the horizon for over haemophilia A and A functional cure for haemophilia B (the haemophilia? 20 years. It is now close rarer form) were The current to becoming a licenced underway globally. therapies in clinical We are working with therapy. trials are also onethe haemophilia off therapies as clinicians to provide the opportunity the person will develop antibodies for some people with haemophilia to the AAV, thereby preventing in Ireland to participate in some of retreatment. Work is ongoing to allow these clinical trials. retreatment in the future. For most In March this year, we announced of the clinical trials, individuals with that the first Irish person with pre-existing AAV antibodies are also haemophilia B had been treated with excluded. The Factor IX trial here is gene therapy as part of a clinical trial. an exception as, with this particular Since then, the number of people vector, those with pre-existing treated has been increased to three. antibodies can be included without All three individuals are reported to damaging the effectiveness. be doing well. Questions remain regarding the range of factor expression we will Findings so far see and the duration of expression, In the earlier dose finding study, but the long-cherished hope of FIX levels six months post infusion seeing gene therapy and a possible ranged from 33% to 57%. This functional cure for haemophilia is changed the individual from now visible on the horizon. having severe haemophilia to mild
Hospital-acquired VTE A number of risk factors have been identified as being associated with an increased risk of VTE. Major surgery, active cancer, prolonged immobilisation with medical illness and traumatic injury with limb fracture are among the most clinically significant VTE risk factors encountered in clinical practice. Other risk factors include pregnancy, oestrogen therapy and long-haul travel. However, while VTE may arise for different reasons in different people, the majority of all these VTE events occur during admission to hospital. This is likely because multiple transient VTE risk factors frequently arise among hospital in-patients (such as immobility, acute infection/ inflammation, major surgery etc.). Crucially, while VTE is common in hospitals, high-quality data has consistently demonstrated that the majority of these VTE events are preventable, provided appropriate steps to reduce VTE risk are taken.
Dr Barry Kevane Consultant Haematologist, Mater Misericordiae University Hospital & Ireland East Hospital Group
Effective VTE prevention strategies consist primarily of the use of validated clinical risk assessment tools (to identify high-risk patients) followed by the appropriate use of pharmacological thromboprophylaxis with anticoagulant medicines to reduce the chance of blood clotting during these high-risk periods. As most instances of HA-VTE are preventable, deaths associated with HA-VTE are also likely to be preventable in many cases. The implementation of standardised VTE prevention strategies in other countries, including the UK, has been proven to reduce VTE-related mortality in hospitals. Recently, the HSE has made a concerted effort to address the major risk posed by HA-VTE in Irish hospitals. Guidelines for prevention of HA-VTE in Ireland have been published and a HA-VTE national key performance indicator has been introduced for all Irish hospitals to drive VTE quality improvement initiatives.
As most instances of HA-VTE are preventable, deaths associated with HA-VTE are also likely to be preventable in many cases. VTE prevention in the era of COVID-19 COVID-19 is posing challenges across our healthcare system. At an early stage of the pandemic, derangements of blood coagulation were identified as being hallmarks of this infection and as being indicators of poor outcome. Moreover, very high rates of thrombosis have been reported, which are associated with COVID-19, and appear to occur despite standard VTE prevention practices. Clinical trials to determine the optimal prevention strategy are awaited but, in the interim, adherence to existing evidence-based guidelines for VTE prevention and maintaining a high level of vigilance in our approach to VTE prevention is vital.
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New drugs bring hope for lymphoma patients
This article is sponsored by Roche
A novel class of drugs holds promise for patients with diffuse large B-cell lymphoma who don’t respond to first line treatment or relapse.
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Dr Brian Bird Consultant Medical Oncologist, Bon Secours Health System
iffuse large B-cell lymphoma (DLBCL) is the most common type of nonHodgkin lymphoma and over 800 people are diagnosed with it in Ireland each year. However, a third of patients don’t respond to first line treatment or relapse and the options for them are limited. There has been considerable interest in CAR-T therapy in recent years. The treatment, which involves programming a patient’s immune system to target the cancer by re-infusing genetically edited T cells, certainly holds great promise, but it isn’t suitable for everyone. It’s challenging and extremely expensive. Dr Brian Bird, Consultant Medical Oncologist at Bon Secours Health System, is keen to highlight other, potentially more accessible, new treatments. “There are more options for elderly people who don’t respond to first line chemotherapy or where a transplant hasn’t worked or isn’t an option. The one that’s going to be most relevant to the greatest number of people are antibody-drug conjugates,” he confirms.
Treatment options As it currently stands, the first line treatment for most DLBCL patients is a combination of chemotherapy drugs known as R-CHOP. For patients who don’t respond or relapse, the next option is an autologous hematopoietic stem cell transplant followed by high dose chemotherapy. Transplants are lengthy, risky and not generally considered for anyone over 70. “Of the third of people who relapse, only half of those will be fit to start a transplant and only half of those will be cured. That leaves us with an unserved population,” confirms Dr Bird. For this “unserved population” there are few alternatives, which is why trials currently taking place into antibody-drug conjugates (ADCs) are so exciting. This novel treatment combines powerful cancer drugs with an antibody that allows them to be delivered directly to cancer cells, which limits damage to healthy cells. Benefits of antibody-drug conjugate ADCs are already licensed for use in the US and EU but not reimbursed in Ireland and Dr Bird believes they
could bring fresh hope to forgotten patients with DLBCL in Ireland. “It seems to be well tolerated in frail and elderly patients with co-morbidities. I don’t think it’s a cure for the majority of patients, but it’s a very helpful drug in terms of prolongation of life,” confirms Dr Bird. Other research is taking place into therapies, such as cell signal blockers, other antibodies, bispecific antibodies, and checkpoint inhibitors, that have already been used to successfully treat other lymphomas. However, Dr Bird is hopeful that the phase three trial currently taking place into the efficacy of ADCs in first line DLBCL will mean that patients in Ireland could benefit within the next few years. “I do think that drugs like this are important advances in this population and would be optimistic that it may move into earlier lines of treatment, should the clinical trials be positive.” he concludes. Written by: Kate Sharma Veeva no- M-IE 00000097 Date of preparation June 2020
Well-known chronic complications of VTE include a potentially life-threatening pulmonary vascular disease called chronic thromboembolic pulmonary hypertension, and post-thrombotic syndrome; a disorder characterised by chronic pain, swelling and ulceration of limbs affected by deep vein thrombosis.” ~Dr Barry Kevane
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