Understanding Haemoglobinopathy Care in the UK: A Comprehensive Study

2. Rationale for the study • Changing pattern of care in the UK • Developing protocols • New interventions • High birth incidence • Latest newborn screening figures predict between 1:2000 and 1:2500 • High rate of admissions • 13,000 finished episodes in London 2005-06 • Quality of autopsies • No previous national audits of deaths with casenote review

3. Study overview • All haemoglobinopathy deaths in the UK over a 2 year period • Data collection period • 1st January 2005 – 31st December 2006 • ICD-10 codes D56 (Thalassaemia) and D57 (Sickle Cell Disease) • Anywhere in diagnosis or cause of death • Adults and children • Hospital and community deaths

4. Inclusion criteria • Patients with the following haemoglobinopathies included: • Sickle cell anaemia (HbSS) • Sickle haemoglobin C (HbSC) • Sickle haemoglobin D (HbSD) • Sickle β-thalassaemia (HbS βThal) • β-thalassaemia major • β-thalassaemia intermedia • Exclusions – Patients with traits and no clinical symptoms

5. Study aims • Primary aim: to collect information on the care received by haemoglobinopathy patients who die in order to identify remediable factors in the care of these patients. • Issues addressed included: • The organisation of outpatient management • Experience in managing haemoglobinopathies • Pain management • Mortality associated with surgery • Patterns of clinical pathology • The availability and use of local guidelines and protocols

6. Data collection • Semi structured questionnaire – 3 sections • The patient’s regular management • Final clinical episode • Organisation of care • Last 6 months medical notes • GP/specialist centre notes • Hospital casenotes • Autopsy reports (if available) • Guidelines and pathways – local and national • Expert opinion from advisors (assessment form)

7. Number of cases identified Denominator: 47 questionnaires; 55 casenotes

8. Exclusions • Of the 93 cases excluded, the majority were thalassaemia trait and asymptomatic sickle cell traits • High frequency with which this irrelevant data was entered onto death certificates indicates: • lack of understanding of clinical consequences of condition • lack of awareness of how to fill in death certificate • One very elderly patient with thalassaemia trait • thalassaemia listed in part 2 of death certificate • patient in fact died of cancer

9. Thalassaemia and sickle cell traits • Key finding: A disproportionately large number of cases with thalassaemia trait and sickle cell trait were reported to NCEPOD when the trait was not relevant. • Recommendation: In our multi-racial society, it is essential that all doctors should have a basic understanding of thalassaemia and sickle cell trait. (General Medical Council) • Recommendation: Sickle cell trait and thalassaemia trait should rarely be included on the death certificate; and if included this should only be after review by an individual who has experience in haemoglobinopathies. (Pathologists) • However, sickle cell trait is not always benign…

10. Sickle cell trait – case study 1 A young patient with sickle cell trait presented with haematuria and other kidney problems. Investigations showed that they had metastatic renal medullary carcinoma. The patient subsequently died. The advisors were of the view that this rare type of renal carcinoma is virtually restricted to those with the sickle gene, particularly HbAS, HbSC and occasionally HbSS. The prognosis for this carcinoma is very poor, and survival is less than one year from diagnosis.

11. Method of identification

12. 31/55 patients male • 6 paediatric cases • Age range 1 to 77 years

13. Age of patients at death

15. Place of death • Hospital deaths most common • 41/55 died in hospital • 14/55 in community; 3 within 14 days of discharge • Of these 3, cause of death unknown in 2

16. Duration of final admission

17. Patterns of death - overview • Thalassaemia patients (n = 7) • Adult sickle cell disease patients (n = 40) • HbSC patient subset (n = 10) • Paediatric sickle cell disease patients (n = 6) • later in presentation with paediatric management • Sickle cell trait patients (n = 2) not included in this section on main patterns of death

18. Thalassaemia – patterns of death • 7 patients with thalassaemia died • 3 with thalassaemia intermedia (ages 39-58) • 4 with thalassaemia major (ages 19-32) • 2 died of complications of thalassaemia • 1 with cardiomyopathy • 1 with mucormycosis (co-morbidity diabetes) • Other 5 patients died of non-related causes • 2 died of cirrhosis • 1 of carcinoma of the lung • 1 with possible sepsis • 1 with no documented cause of death

20. HbSC adult patient subset • 10 patients with age range 26-74 years • Only 2 had causes of death attributable to sickle cell disease • Intracerebral haemorrhage • pulmonary embolism • 5 patients died of unrelated causes • 1 each with brain tumour, diabetes and advanced HIV disease • 2 patients with severe systemic lupus erythematosus • co-incidental/pathogenic link? • 3 with unknown cause of death

21. NCEPOD grading of care • Good practice: A standard that you would accept from yourself, your trainees and your institution • Room for improvement: Aspects of clinical care that could have been better. • Room for improvement: Aspects of organisational care that could have been better. • Room for improvement: Aspects of both clinical care and organisational care that could have been better. • Less than satisfactory: Several aspects of clinical and/or organisational care that were well below satisfactory. • Insufficient information: Insufficient information available to assess the quality of care.

24. Regular management Type your headline here Regular management

25. Regular management • NCEPOD looked at the following aspects of regular management: • regular medications • antibiotic prophylaxis • vaccinations • location of patient management • outpatient appointments • medical advice and treatment • regular attenders • pain management (separate chapter)

26. Vaccination status

27. Vaccinations • Key finding: The clinicians managing the patients in this study only reported 15/47 as having received pneumococcal vaccine. • Recommendation: There needs to be clear recording of vaccination status by default; liaison between primary and secondary care is needed. (Primary and Secondary Care Trusts) • Recommendation: As a minimum, the Department of Health guidance regarding vaccination and prophylactic antibiotics should be followed in order to prevent sepsis from hyposplenism. (Primary Care Trusts)

28. Outpatient management • Outpatient management took place in specialist centres, GP surgeries and non-specialist centres • 28/47 patients attended outpatients • 12 of these were reported to attend irregularly • 11/55 patients showed a reluctance to attend outpatients • In 4 cases it was judged to have had an impact on outcome • Further 3 cases with insufficient information to comment

29. Refusal to accept advice • In 8/14 patients who refused advice/treatment, the advisors considered that it could have had impact on outcome • e.g. thalassaemic patient refusing advice to increase chelation

30. Pain management

31. Pain management • Pain is the most frequent problem experienced by individuals who have sickle cell disease (SCD) and has a major impact on quality of life. • Good pain management is a key requirement for the care of sickle cell patients • Many complicating factors for both clinicians & patients • Guidelines exist for acute painful crisis management British Journal of Haematology, 2003, 120, 744–752 • NCEPOD reviewed • Ongoing pain management • Acute pain management

32. Ongoing pain management • Of the 40 sickle cell disease patients for whom a questionnaire was returned, 14 took regular pain medications for ongoing pain management • In the opinion of the advisors, in six patients there was evidence of dependency issues; however in 13 patients there was insufficient information from the casenotes to form an opinion • In general, there was a lack of a multidisciplinary or multi-agency approach to the management of opioid dependency in these sickle cell disease patients

33. Pain management - case study 5 • A young patient with sickle cell disease was known to have a drug dependency and was receiving opioids on a regular basis. They sought help from a sickle cell centre. The patient was allowed to leave the clinic before arrangements had been made for them to be seen by a psychologist working for the drug dependency team. The patient did not return to the clinic and their body was discovered some two weeks later. • Allowing patient to leave before support had been organised may have contributed to the subsequent tragic events. • The quality of the autopsy was poor. Noteworthy that “a white substance was found in the stomach and in the trachea”. It is most likely that this person had vomited and died from aspiration of vomit. It was likely that this was directly due to opioid misuse.

34. Acute pain management • Of the 35 sickle cell disease patients who died in hospital, 19 had pain as an admitting complaint. • In 13 of these patients there was lack of evidence that pain or the adverse effects of opioids were formally assessed on a regular basis. • Of those patients who did have pain or adverse effects monitored, the frequency of observations was inadequate

35. Acute pain management • In 9/19 of the patients admitted with pain, excessive doses of opioids were given • In 5 patients where complications occurred due to overdose this contributed to the ultimate death • In 7 of the patients who received excessive doses of opioids there was lack of knowledge regarding acute pain management and inadequate clinical review of the escalating analgesic requirements • In all of these, junior trainee medical staff were responsible for the prescribing of analgesia and no apparent attempt was made to seek advice from consultants in haemoglobinopathies or acute pain management.

36. Acute pain management – case study 6 • Middle aged patient with HbSC admitted via the emergency department - back and leg pain of 24 hours duration • patient was not taking any regular analgesia • initially given diclofenac and co-codamol according to a local sickle cell crisis analgesia regimen • minimal improvement in the pain • Prescribed 50mg of pethidine IM 4 hourly post-admission followed by 100mg 2 hourly by a pre-registration house officer • No evidence of formal assessment or documentation of pain. • Following evening, SHO was asked to insert an intravenous cannula for fluid administration • found the patient unresponsive • could not be resuscitated

37. Case study 6 – advisors’ opinion • This opioid naïve patient had received 1500mg of pethidine in the 24 hours leading up to their death which was thought to be excessive • The patient should have had more frequent observations of the level of sedation and respiratory rate which reflected the increasing doses of opioids • There was lack of senior medical staff involvement in this patient’s care • The opioid overdose was a probable contributing factor to this patient’s death which could have been avoided. Despite an autopsy, there was no convincing clinical pathology

38. Pain recommendations • Recommendation:A multidisciplinary and multi-agency approach is needed in the ongoing pain management of patients with sickle cell disease – essentially this takes place outside hospitals for the majority of patients. (Primary and Secondary Care Trusts) • Recommendation:Regular assessment of acute pain, sedation and respiratory rate should be undertaken and recorded for all patients admitted with sickle cell disease. The frequency of these observations should reflect the degree of pain and dose of opioids administered, to allow recognition of opioid overdose. The development of “track & trigger” systems would greatly enhance better pain control and patient safety. (Clinical Directors)

39. Final clinical management

40. Final clinical management • NCEPOD looked at the following aspects of management in the final clinical episode: • Stroke • Acute chest syndrome • Pulmonary embolism & hypertension • Sepsis • Iron overload and cardiac death • Renal failure • When sickle is not the main problem • Surgery and peri-operative care • Pregnancy • Paediatric patients • Nursing care • Other issues – protocols/education

42. Stroke • Stroke was the commonest complication, leading to death in 9 patients • All the formally diagnosed cases in adults were haemorrhagic • May have been some ischaemic cases, but this was not possible to determine • No guidelines for the prevention of stroke in adults at present, as it is less tractable, but there are for children

43. Acute chest syndrome (ACS) • 2 cases where ACS was listed as primary cause of death • 3 further cases where it was likely contributor or part of multi-organ failure • No documented cases in children, although a recognised cause of death in paediatric patients • Recommendation:Acute chest syndrome is a major cause of morbidity and mortality in patients with sickle cell disease. Management of patients with this complication should be according to local protocols and early advice from specialists in essential. (Primary and Secondary Care Trusts)

44. Pulmonary embolism & hypertension • 2 patients died of massive pulmonary embolism • Both diagnosed at autopsy • Advisors commented on potential difficulties associated with diagnosis • Especially chronic progressive lung disease • Recommendation:Chronic sickle chest disease is an expanding, complicated area and requires more careful correlation of pre-mortem clinical, physiological and imaging data with autopsy pathology. (Clinicians and Pathologists)

45. Renal failure • People with sickle cell disease are known to be particularly prone to developing kidney failure • May be due to damage to: • the renal glomerulus by the sickle process • sickling in the medullary vessels – papillary necrosis • infection • the use of non-steroidal anti-inflammatory drugs • No one dying in hospital was recorded as having renal complications of sickle cell disease as a cause of death • one patient with chronic disease allowed to die at home • one patient in which renal failure potentially overlooked • Care associated with examples of very best and very worst care

46. Renal failure – case study 12 • Young patient admitted with breathlessness, anaemia and urea of 27 mmol/L. • Comment in notes that serum creatinine should be measured before decision made re: renal failure • no evidence that this was followed up • Breathlessness diagnosed as ACS • review by chest physician doubted this; suggested fluid overload • again, no follow up of renal function • A little later, patient died of cardiac arrest • blood gas sample potassium result led to a diagnosis of ‘hyperkalaemic cardiac arrest’

47. Case study 12 – advisors’ opinion • The advisors considered this to be an unexpected death. • There was a review of the case, but no-one appeared to have noted the initial high blood urea resulted. • It was evident that the patient has had renal failure on admission which was not reconsidered. • The focus appeared to have been on the chest problems and adequate attention was not paid to the complete picture.

48. A different problem – case study 13 A young adult patient was thought to have an acute sickle cell crisis, but with rather atypical features. There did not appear to be a good response to standard treatment and the clinicians later reconsidered the working diagnosis. Further investigations showed the patient was HIV positive, with end-stage disease, which fitted better with the clinical scenario. The advisors commented that had it not been for the sickle cell disease, it is likely that the problem would have been recognised more promptly. HbSC appears to have stopped the clinicians thinking beyond the patient’s sickle cell disease.

49. When sickle is not the main problem • Key finding: Patients with sickle cell disease can have other conditions which can be misattributed to sickle cell disease. • Recommendation: All staff should be aware that people with sickle cell disease re subject to the diseases that other patients suffer from as well. If there is uncertainty as to whether the problem is sickle cell related, advice should be sought from an experienced clinician. (Primary and Secondary Care Trusts)

50. Surgery and peri-operative care • 9/41 patients underwent surgery • Seniority and experience of surgeon and anaesthetist • considered to be sufficiently experienced in 4 cases • insufficient data to judge in remaining 5 cases • 7 patients experienced peri-operative complications • considered to be avoidable in 4 cases • worsening liver failure and ascites, massive cerebral infarct, massive bleed and post-operative sepsis • Key finding: There were fewer surgical cases submitted than were anticipated. NCEPOD is also aware of the ongoing study of pre-operative blood transfusion.