Peter Clive Higson

ee
Department
| of Health

POC1_818413

Mr M Burgess

From the Rt Hon Jeremy Hunt MP
Secretary of State for Health

Richmond House
79 Whitehall
London

SWIA 2NS

‘Tel: 020 7210 3000
- Mb-sofs@dh.gsi.gov.uk

Assistant Coroner

HM Coroner’s Court

Station Approach

Woking ;

Surrey 20 DEP 2013
GU22 7AP

De ha, Owyess,

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’s Disease.

You conclude that the deceased died from a complication of a necessary therapeutic
procedure.

You raise the following concerns that:

i) 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 Department 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.

A number of points in NHSBT’s report are particularly relevant.

e 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.

e The steps taken by NHSBT, when notified of the case, to investigate the platelet
transfusions. They established that the donors had been appropriately selected
to minimise the risk of transfusion-related acute lung 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 for 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’s situation, or that action is required to
prevent future deaths in similar circumstances.

I attach NHSBT’s full report for information.

I hope that this response is helpful and I am grateful to you for bringing the
circumstances of Mr Higson’s death to my attention.

Mum ying

Aye

JEREMY HUNT

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 a complication of a necessary
therapeutic procedure.

NHSBT was provided with the following clinical background by the Coroner: “The
deceased had suffered from Hodgkin's 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 a 21 day course of Co-Trimoxazole and with
Methylprednisolone. His chest remained an issue, however, and he underwent a
platelet transfusion of 2 pools of platelets on 12th and 13th March which made
matters worse. His clinical situation looked like a transfusion related acute lung
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 ceil 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. A 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’s 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 a designated TRALI expert within

NHSBT (Dr (J for London and South East Region). As the Coroner’s report
was the first notification NHSBT had received of this matter, Dr EE contacted

both (Lead Transfusion Practitioner) and Professor
(Consultant Haematologist) at Frimley Park Hospital. Ms IJ and Prof
HM reviewed the case notes.

Coroners Report: TRALI referral TOO-13-16 Page 1 of 10

NHSBT were informed by a: :: platelets were transfused on 11th March
2013 at 19.10hrs and 13th March 2013 at 12.25hrs and 15.20hrs. The platelets
transfused on 13" 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 lung injury (ALI) suspected to be TRALI in the
notes is on the 15th March at 12.22hrs so platelet transfusions subsequent to that time
were not examined.

NHSBT records showed that the index apheresis platelet unit G0525 1335 7413 A
was collected from a male apheresis donor (53 donations, 44 platelet donations).
Donation G0525 1334 7540 S was collected from a 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 lung 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 or other factors
may be a 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 Page 2 of 10

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. A 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 BB consuitant 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 Page 3 of 10