Iron level monitoring and control
18. Myelofibrosis is a condition with no cure. It is a progressive disease that affects each person differently. People with myelofibrosis receive regular blood transfusions, which means they are at a greater risk of developing iron overload.
19. Iron overload is a condition where there is excess iron in the body that can lead to serious conditions such as diabetes, heart problems, and liver disease. Iron overload can occur when iron levels are not controlled or monitored in these patients.
20. Iron chelation therapy (the removal of excess iron from the body using drugs) can be given to patients who receive regular blood transfusions to prevent iron overload.
21. There is no specific UK or international guidance on the monitoring or controlling of iron in patients with myelofibrosis. However, our haematology adviser told us it is appropriate to refer to guidance for other similar bone marrow conditions. As such, we have considered guidance relating to a similar condition called myelodysplasia. This is because it is a bone marrow condition in which the patient receives regular blood transfusions and is at risk of developing iron overload.
22. BSH’s ‘Guidelines for management of adult myelodysplastic syndromes’ (the BSH Guidance) says patients should be considered for iron chelation therapy at the time they have received 20 units of blood, or when their ferritin level is more than 1,000 μg/l, and that these levels should be checked every 12 weeks. It says studies conducted indicate that within three years of diagnosis, patients receiving regular blood transfusions are more likely to have developed heart and liver disease and that iron chelation therapy can prevent or delay these problems.
23. The BSH Guidance also says says desferrioxamine is the most efficient iron chelation drug to use, but should be stopped if a patient’s ferritin levels drop below 1,000 μg/l. The EMC’s ‘Manufacturer’s recommendations for the use of desferrioxamine’ (the EMC Guidance) says desferrioxamine therapy should be commenced after the first 10 to 20 blood transfusions, or when there is evidence from clinical monitoring that chronic iron overload is present. It describes evidence of chronic iron overload as being a ferritin level of more than 1,000 μg/l.
24. The BJH’s ‘Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias’ (the BJH Guidance) says ferritin levels can become raised for many reasons such as tissue damage and inflammation but, an increase in ferritin levels can be a sign of iron overload. Therefore, increased ferritin levels should be considered within the context of the situation.
25. Our haematology adviser told us the Trust would not be expected to administer iron chelation therapy to Mr U unless it provided him with a clear benefit. They told us this decision would be dependent on several factors, including Mr U’s prognosis (probable course and outcome of his condition) and his own views.
26. For example, if Mr U’s prognosis was such that he was expected to die before the effects of iron overload would cause his significant harm, they would not expect the Trust to provide it. This is because the benefit of providing iron chelation therapy would not outweigh the side effects of it which include pain, discomfort, and nausea.
27. This is because the GMC’s ‘Good Medical Practice’ (the GMC Guidance) says clinicians must prescribe drugs or treatment only when they have adequate knowledge of the patient’s health and are satisfied the drugs or treatment serve the patient’s needs. It says clinicians should adequately assess a patient’s condition, taking account of their history, including their symptoms, views, and values. It also says clinical records should include relevant clinical findings, decisions made, and actions agreed, and the information given to patients.
28. Further, the GMC Guidance says assumptions should not be made about the information a patient might want or need, and that patients should be told of any treatments the clinician believes have a greater potential benefit than those they or their organisation can offer.
29. In other words, we would expect to see evidence the Trust assessed Mr U’s condition and prognosis, discussed this with him, provided information and advice where necessary, and recorded this clearly in his clinical records. Further, if the Trust decided to provide Mr U with iron chelation therapy, we would expect to see evidence the Trust did so in line with the BSH Guidance, BJH Guidance, and EMC Guidance set out above, and clearly documented the reasons for its decisions.
30. Mr U was diagnosed with myelofibrosis in June 2019. We can see from the evidence available to us he received regular blood transfusions from July 2019 until his death in March 2022.
31. However, we have seen no evidence the Trust carried out an assessment of Mr U’s prognosis at the point of diagnosis. We have also seen no evidence it discussed with him the risk of iron overload that would likely arise from the blood transfusions he was going to receive, how this may affect him in the long term, and his treatment options, whether available at the Trust or elsewhere.
32. As such, this was not in line with the GMC Guidance, and we consider this to be a failing. We will revisit the impact of this later.
33. Mr U received blood transfusions from July 2019 and by the end of August 2019 he had received 20 units of blood.
34. Our haematology adviser told us from this point it was predictable that Mr U would develop iron overload continuing with his blood transfusion programme. The Trust did not start iron chelation therapy once Mr U had received 20 units of blood, as recommended by the BSH Guidance and EMC Guidance. We have seen no evidence the Trust considered whether to start iron chelation therapy at this point, including whether it discussed it with Mr U, or that it documented the reasons for the decision in his clinical records.
35. We have also seen no evidence the Trust proactively monitored Mr U’s ferritin levels from June 2019 to June 2021 (which the BSH Guidance says should have been checked every 12 weeks) or that it checked whether Mr U was developing iron overload.
36. As such, this was not in line with the BSH Guidance, EMC Guidance, and GMC Guidance and we consider this to be a failing. We will revisit the impact of this later.
37. In June 2021, Mr U’s GP checked his bloods and confirmed he had iron overload. The Trust subsequently gave Mr U iron chelation therapy fortnightly, in the form of desferrioxamine, from July 2021 until May 2022. This amounted to a total of 22 occasions.
38. We have seen no evidence the Trust discussed its decision to start iron chelation therapy with Mr U, or the consideration it gave before making this decision. We can also see the frequency it was given at is less than the five to seven times a week recommendation set out in the EMC Guidance.
39. The Trust told Miss U during the complaints process Mr U was not given iron chelation therapy initially because he was treated ‘within a palliative setting’ and that it was not a funded option for patients like him. It also told her treatment for iron overload in patients with myelofibrosis and similar bone marrow conditions does not impact the overall clinical outcome for patients at risk of iron overload from blood transfusions.
40. However, during our investigation the Trust told us:
• It did not give iron chelation therapy in line with the recommended frequency because it thought it was too toxic and intrusive for Mr U. It said it provided it at the lesser frequency to give Mr U the impression it was doing something for him.
• After retrospectively assessing Mr U’s prognosis using a formula known as a DIPSS-Plus, Mr U had a DIPSS-Plus score of 4. It told us this gave Mr U a 50% chance of surviving for 16 months from his myelofibrosis diagnosis in 2019.
• It did not consider Mr U was receiving ‘palliative treatment’ because although he was receiving palliative care (because his condition was not curable) he did not have a very short prognosis, or a condition that was considered to be terminal.
• A ‘more effective’ iron chelation therapy, which is given at home, is not a funded option it offers to patients, but the iron chelation therapy it gave Mr U in 2021 was funded and available in 2019.
41. This means there are contradictions between what the Trust told Miss U during the complaints process, and what it has told us during our investigation. Our ‘NHS Complaint Standards’ say organisations should be clear about the facts, admit when things go wrong, and seek to take learning from complaints.
42. We recognise the Trust’s retrospective DIPSS-Plus calculation gave Mr U a 50% chance of living 16 months from his myelofibrosis diagnosis. However, the Prognostic Study outlined on page 3 shows this score also meant Mr U had a 20% chance of surviving more than three years. Our haematology adviser says a DIPSS-Plus score of four means there was a good chance Mr U would live long enough to develop clinically significant iron overload and this therefore should have been discussed with him on several occasions as we have explained.
43. The evidence shows the Trust was not acting in line with the EMC Guidance and GMC Guidance between July 2021 and May 2022, and that it did not act in line with our ‘NHS Complaint Standards’ when it responded to Miss U’s complaint. We therefore consider this to be a failing and we will revisit the impact of this later.
Albumin administration
44. Miss U complains the Trust failed to provide Mr U with IV albumin during the ascitic drain procedure he underwent on 9 March 2022. The purpose of an ascitic drain is to drain ascites. Ascites is a build-up of fluid in the abdomen and is one of the most common indicators of chronic liver disease.
45. On 11 January 2022, Mr U underwent an ascitic tap procedure. The purpose of the ascitic tap is to diagnose the cause of the ascites. The results from this diagnostic test confirmed the ascites was due to chronic liver disease.
46. Our hepatology adviser told us it is common for patients who have myelofibrosis and regular blood transfusions to develop chronic liver disease. This was identifiable by the low albumin and protein in the sample taken. The results also confirmed there was no infection in the ascites, which meant there was no further course of treatment the Trust needed to provide aside from removing the fluid build-up via an ascitic drain.
47. When Mr U underwent the ascitic drain procedure on 9 March 2022, the Trust drained all seven litres of fluid present at the time. Our hepatology adviser told us it is standard practice to drain ascites up to dryness. The BSG’s ‘Guidelines on the management of ascites of cirrhosis’ (the BSG Guidance) also says ascites should be ‘drained to dryness in a single session as rapidly as possible’. This is to help prevent possible infection and other complications that could arise from leaving ascites present in the body.
48. However, the BSG Guidance also says that for every two to three litres drained, one unit of IV albumin should be given to help support the kidney function to prevent the patient from becoming unstable and developing serious issues with their kidneys.
49. Our hepatology adviser told us Mr U should have been given two units of IV albumin and, although Mr U had an underlying haematological cancer, and between January and March 2022 had been found to have a small early colon cancer, the ascites was not malignant (cancerous).
50. This is evident because the results of Mr U’s diagnostic ascitic tap procedure in January 2022 showed his ascites had a serum ascites albumin gradient (SAAG) of greater than 11. SAAG is a calculation used to help determine the case of ascites in a patient. Our hepatology adviser told us that if the cause of the ascites was cancer, the SAAG would have been less than 11.
51. They told us there is no documented rationale in the clinical records to explain why IV albumin was not given and, although the Trust has told us in response to our enquiries that it did not give IV albumin because the ascites was caused by malignancy, we are persuaded the evidence does not support this.
52. As such, we think the Trust failed to give Mr U IV albumin in line with the BSG Guidance and therefore consider this to be a failing.
Impact
53. As outlined above, we have found the Trust:
• failed to monitor and control Mr U’s iron levels between 2019 and his death, including failing to discuss the risks of developing iron overload and the treatment options available to him on several occasions, in line with the guidance we have seen.
• failed to provide IV albumin to Mr U during his ascitic drain procedure on 9 March 2022 • provided responses to Miss U’s complaint that were unclear, contradictory, and not supported by the evidence.
54. Miss U has told us the Trust’s poor care led to Mr U developing iron overload. She says this led to heart complications, blurred vision, and problems with his abdomen. She says these problems may have led to his death. She also says once the iron chelation therapy was started in July 2021, Mr U’s ferritin levels improved.
55. We recognise how distressing this experience has been for Miss U and her family. They saw Mr U gradually deteriorate over several years and when his complications became more frequent, he felt more scared and ‘helpless’. We understand this was distressing for them all.
56. To understand the impact of these failings, we sought advice from our haematology adviser, our hepatology adviser, and our cardiology adviser. We have set out a summary of their advice, and our consideration, below.
Haematology advice
57. It is not possible to say whether the iron overload Mr U developed led to the complications he experienced, and Miss U describes. Iron overload can lead to a variety of symptoms including heart and liver failure, abdominal pain, swelling, and loss of vision. These can also occur due to other factors.
58. However, our haematology adviser told us it was unlikely to be the cause of Mr U’s blurred vision that required corrective surgery. This is because Mr U’s eye complications are documented as being glaucoma (high pressure within the eye) and a cataract (a cloudiness of the lens in the eye). These are common in people who do not have iron overload. Glaucoma and cataracts can also be caused or worsened by a steroid called prednisolone, which Mr U was taking.
59. Further, it is possible, but not certain, Mr U experienced some symptoms that were caused by the iron chelation therapy the Trust provided from July 2021. Iron chelation therapy can be unpleasant and there are known side-effects including nausea and sickness, pain, and discomfort.
60. The clinical records on 1 October 2021 say Mr U reported nausea, restlessness, fatigue and shivers which he attributed to the iron chelation therapy and specifically, the desferrioxamine. However, there are no other reports of any other symptoms in the clinical records and these can also be caused Mr U’s general ill-health.
61. Finally, while Mr U’s ferritin levels improved between June 2021 (8,537 μg/l) and February 2022 (7,565 μg/l) when he was receiving iron chelation therapy, he remained significantly overloaded with iron. During this period, his ferritin levels fluctuated, rather than there being a steady decline. As explained earlier, ferritin is not directly influenced by iron levels, and fluctuations can be caused by other things such as tissue damage and inflammation. As such, the overall improvement is unlikely to be because of the iron chelation therapy that was commenced in July 2021.
Hepatology advice
62. Our hepatology adviser told us Mr U had myelofibrosis since 2019, which is a cancer with no cure. He was also later suspected to have developed colon cancer and he had developed an ascites. Overall, this meant Mr U was unwell before he underwent the ascitic drain procedure. While it is possible a lack of albumin could lead to serious complications such as kidney failure resulting in death, this is unlikely in Mr U’s case.
63. Firstly, this is because Mr U’s kidneys had been checked two weeks before the procedure and they were only mildly impaired which means it is unlikely a lack of albumin during that procedure would cause such a drastic decline in kidney function resulting in kidney failure.
64. Secondly, if the lack of albumin administration during the ascitic drain procedure had been contributory to his death, you would expect to have seen other immediate complications such as a large internal bleed or pulmonary oedema (excessive fluid build-up in the tissue or air spaces of the lungs). However, this is not the case based on the evidence available.
Cardiology advice
65. Our cardiology adviser said Mr U underwent an echocardiogram (ECG) in August 2021 and this showed he had aortic stenosis which is a condition that affects the valve that lets blood out of the heart. They said in Mr U’s case this was caused by calcium build-up on the valve which meant the blood could not leave the heart as easily, therefore causing a strain on the heart. They said this cannot be linked to Mr U’s iron overload.
Our view
66. With the above in mind, we cannot say the failings we have identified led to Mr U’s death. This is because we cannot say Mr U should have been given iron chelation therapy from the outset, but rather that this option should have been considered and explored, and Mr U’s input sought.
67. We also cannot say the iron overload Mr U developed led to the complications described by Miss U. This is because while iron overload can lead to some of these complications the evidence available to us suggests there were other causes for these conditions that are not linked to iron overload.
68. Further, we cannot say if the iron chelation therapy did lead to Mr U experiencing any of the possible side effects. While there is a record that Mr U was experiencing some possible symptoms of iron chelation therapy one month after starting this treatment, there are no further reports of symptoms. We also see there are other possible causes of the symptoms Mr U reported shortly after starting the therapy. On that basis we are unable to conclude with any certainty, the therapy was responsible for his symptoms.
69. We recognise this means there is uncertainty as to whether Mr U’s outcome could have been different, or the true extent of the impact on Mr U.
70. If the Trust had assessed Mr U’s prognosis when he was diagnosed with myelofibrosis and discussed his options with him, he may have made decisions that would have affected the course of treatment he then received in subsequent years. Sadly, there is no way of knowing what Mr U would have done or, if after consulting him, the Trust would have done things differently.
71. We think this is likely to cause Miss U significant distress and uncertainty.
72. We also think Miss U will be distressed to learn that the Trust gave Mr U iron chelation therapy from July 2021 even though it did not think it would have a clinical benefit. We think the fact the Trust has admitted to giving this treatment to appease him, when it carried the risk of side effects, will be extremely upsetting for her.
73. Sadly, we think Miss U will be left knowing things were not done correctly, and wondering if things could have played out differently had they been. This will stay with her beyond the conclusion of our investigation and is therefore an injustice that the Trust has not yet put right.