From the Rt Hon Jeremy Hunt MP Secretary of State for Health Department of Health Richmond House 79 Whitehall London SWIA 2NS POCI_818413 Tel: 020 7210 3000 Mr M Burgess Mb-sofs@dh-gsigovuk Assistant Coroner HM Coroner' s Court Station Approach Woking Surrey 2 0 DFc 2013 GU22 7AP e Mu 0~jej'_ Thank you for your letter following the inquest into the death of Peter Clive Higson, In your report you state that Mr Higson died from Myocardial Infarction and Acute Respiratory Distress Syndrome and Treated Hodgkin'$ Disease. You conclude that the deceased died from a complication of a necessary therapeutic procedure: You raise the following concerns that:
1) the platelet transfusion following the stem cell transplant seemed to have a major detrimental effect on the deceased and; ii) a question arises as to whether there was any aspect of the stem cell transplant interacting with the platelet transfusion suggesting that On occasions such transfusion might be contra-indicated, The tment has sought information and advice from NHS Blood and Transplant (NHSBT). NHSBT provides blood for transfusion to the NHS, and has expertise in transfusion medicine. NHSBT provided a report on the circumstances leading up to the death of Mr Higson, together with information on the measures in place to minimise the risk of an adverse outcome to a platelet transfusion. On the basis of this, it appears that prophylactic platelet transfusion was an appropriate treatment for Mr Higson, and that the respiratory deterioration leading up to his death is likely to have resulted from causes other than the transfusion. Depart

number of points in NHSBT's report are particularly relevant; The recent randomised study in the UK and Australia which investigated the risks and benefits of prophylactic platelet transfusions in patients with haematological cancers, particularly in patients who had received autologous stem cell transplantation, as Mr Higson had, This concluded that the benefit of such a transfusion to reduce bleeding outweighs the risk of the transfusion. The steps taken by NHSBT, when notified of the case, to investigate the platelet transfusions: established that the donors had been appropriately selected to minimise the risk of transfusion-related acute injury (TRALI) (ie one male apheresis donor, who would be less likely to have white blood cell antibodies which can cause TRALI, and one female apheresis donor who had been screened for such antibodies): As TRALI is defined as occurring within 6 hours of transfusion, the length of time (15 hours) between the last platelet transfusion and the main episode of respiratory deterioration suggests there may have been causes other than the transfusion: The range of measures in place to minimise the risk of TRALI including leucodepletion; use of plasma from males to suspend platelets, and screening of both new and existing female apheresis platelet donors the antibodies which can cause TRALI. Given these points, it does not appear that platelet transfusion would be contra- indicated for patients in Mr Higson'$ situation, Or that action is required to prevent future deaths in similar circumstances _ I attach NHSBT'$ full report for information: hope that this response is helpful and I am grateful to you for bringing the circumstances of Mr Higson's death to my attention. n jurh 7h JEREMY HUNT They lung for

NHS Blood and Transplant Response to Regulation 28 Report for HM Coroner for Surrey: Name: Mr Peter Clive Higson DOB: 29/12/1949 (died 22/03/2013) Hospital: Frimley Park Hospital NHSBT Transfusion Related Acute Lung Injury (TRALI) NHSBT Referral Reference Number: TOO-13-16-PH
1. Background NHSBT received a Regulation 28 Report- Action to Prevent Future Deaths from HM Coroner from Surrey dated 23/10/13. The coroner had found the cause of death to be: la - Myocardial Infarction 2 - Acute Respiratory Distress Syndrome and treated Hodgkins Disease. The inquest concluded that the deceased died from complication of a necessary therapeutic procedure: NHSBT was provided with the following clinical background by the Coroner: 'The deceased had suffered from Hodgkin'$ lymphoma On 29th January 2013 he underwent an autologous stem cell transplant at University College Hospital, London after which he was discharged home On 28th February 2013, he became very unwell and was admitted to Frimley Park Hospital and was treated for Pneumocystis Jiroveci Pneumonia with 21 day course of Co-Trimoxazole and with Methylprednisolone. His chest remained an issue, however, and he underwent platelet transfusion of 2 pools of platelets On IZth and 13th March which made matters worse_ His clinical situation looked like transfusion related acute injury which had a detrimental effect on his breathing and overall well-being: He slowly improved but towards the end of the Co-Trimoxazole course, it was learnt that he did not have the Pneumocystis infection. He died on 22nd March 2013. The Coroner raised the following concerns: 'The platelet transfusion (12th & 13th March 2013) following the stem cell transplant (28th January 2013) seemed to have a major detrimental effect on the deceased and features, of only chronologically, in the ultimate chain of causation leading to his death question arises as to whether there was any aspect of
e.g, the stem cell transplant interacting with the platelet transfusion suggesting that on occasions Such transfusion might be contra-indicated NHSBT has compiled this report in response to HM Coroner' $ concerns
2. Action Taken.
2.1 Immediate Corrective Action: For suspected TRALI cases, hospital clinicians contact NHS Blood and Transplant (NHSBT) and provide the clinical details and donation numbers potentially implicated to designated TRALI expert within NHSBT (Dr for London and South East Region) As the Coroner's report was the first notification NHSBT had received of this matter; Dr contacted both (Lead Transfusion Practitioner) and_Professor (Consultant Haematologist) at Frimley Park Hospital. Ms and Prof Ireviewed the case notes: Coroners Report: TRALI referral TOO-13-16

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NHSBT were informed by that platelets were transfused on 1lth March 2013 at
19.1Ohrs and 13th March 2013 at 12.2Shrs and
15.20hrs: The platelets transfused on 13th March 2013 were single donor apheresis platelets with the following donation numbers: G0525 1335 7413 A and G0525 1334 7540S. The main episode of respiratory deterioration was documented on 14th March at
06.20hrs, 15 hours following the most recent transfusion on 13th March: The first documentation of acute injury (ALI) suspected to be TRALI in the notes is on the ISth March at 12.22hrs so platelet transfusions subsequent to that time were not examined_ NHSBT records showed that the index apheresis platelet unit G0S25 1335 7413 was collected from male apheresis donor (53 donations, 44 platelet donations) Donation GOS2S 1334 7540 S was collected from female donor (35 donations, 9 platelet donations). As part of the TRALI preventive programme all female apheresis platelet donors are screened for leucocyte (white blood cell WBC) antibodies. This female donor has been screened for leucocyte antibodies (white cell antibodies which can cause TRALI) and none were identified NHSBT has also recommended that the regulator of blood components; the Medicines and Healthcare products Regulatory Agency (MHRA) and the Serious Hazards of Transfusion (SHOT) UK haemovigilence scheme are informed of the Coroner' s concerns_
2.2 Potential future preventative action: NHSBT has undertaken measures at least as stringent as international peers to reduce the risk of TRALI whilst ensuring that blood components are available for patients who need them. These measures have been successful in reducing the incidence of TRALI and are detailed in the appendix: Acute injury and acute adult respiratory distress syndrome (ARDS) can be caused by other disorders such as a chest infection in the absence of transfusion: It is also hypothesised that infection and other inflammatory processes may increase the risk of a patient suffering TRALI in the "two hit" hypothesis (see appendix for details): The Coroner explicitly questioned whether the stem cell transplant o other factors may be contraindication to platelet transfusion National guidelines supported by randomised studies have suggested that the risk of adverse effects of transfusion (including TRALI) are outweighed by the benefits of reducing the risk of bleeding in patients with low platelet counts following chemotherapy and stem cell transplantation (BCSH 2003). The presence of infection increases the risk of bleeding and hence, despite infection potentially increasing the low residual risk of TRALI; this is outweighed by the risk of bleeding if platelet transfusion is withheld. NHSBT has recently specifically undertaken an international randomised study with NHS hospitals and other organisations investigating the benefits and risks of prophylactic platelet transfusions Most of the patients in the study had received Coroners Report: TRALI referral TOO-13-16

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autologous stem cell transplantation. This study concluded "The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis: significant number of patients had bleeding despite prophylaxis" (Stanworth et al 2013).
3. Conclusion As the respiratory deterioration occurred more than 6 hours after the transfusion, the deceased in this case had other reasons for ALI ARDS and as the female donor had no WBC antibodies the SHOT imputibility criteria would suggest that TRALI was unlikely: Recent studies and current guidelines suggest that the benefits of platelet transfusion in preventing bleeding following chemotherapy and stem cell transplantation outweigh the risk of the transfusions themselves. NHSBT undertakes measures to reduce the risk of TRALI that are at least as stringent as international peers The MHRA and the SHOT haemovigilence scheme record adverse events including respiratory deterioration and, in conjunction with NHSBT and other organisations, identify potential additional interventions to prevent recurrence: This response has been prepared by: Dr Consultant Haematologist; NHS Blood and Transplant Dr Associate Medical Director Diagnostic and Therapeutic Services; NHS Blood and Transplant Date: 6/12/2013 Coroners Report: TRALI referral TOO-13-16 3 of 10 Page