15 Nov 2018

Jehovah’s Witness trauma study probes blood alternatives

What are the therapeutic strategies for those who
choose not to have human blood transfusions?
Image: Medical Facts
by Anne Crawford

Major blood loss after trauma is particularly challenging for physicians when blood is not an option (BNAO) for treatment, as is often the case for patients who are Jehovah’s Witnesses. But there has been little evidence available about the therapeutic strategies that are used in its place.

Now, researchers from Monash University and the Alfred Hospital’s National Trauma Research Institute (NTRI) have conducted a study into some of the alternatives to blood and are interested in further investigating a novel option among them – a synthetic product made from cow’s blood.

Their findings were published in a recent paper in Vox Sanguinis.

Most Jehovah’s Witnesses refuse blood products due to their religious convictions. But if the haemorrhaging they experience in trauma is not adequately managed, critical anaemia may result, and inadequate tissue oxygen delivery can lead to organ failure and death. The mainstay of haemorrhage management is achieving haemostasis, the bodily process causing bleeding to stop, and restoring circulatory volume, ideally with blood products.

Whilst Jehovah’s Witnesses do not strictly refuse all blood products, research has previously shown that morbidity (e.g. cardiac complications, acute renal failure and hypoxic brain injury) and mortality are significantly higher amongst those with severe anaemia who do not accept blood products compared to matched controls receiving red blood cells.

This study evaluated the therapeutic interventions used and outcomes at discharge of 34 patients with traumatic haemorrhage who identified as Jehovah’s Witnesses at the Alfred Hospital between January 2010 and January 2017. Although this number was low – representing approximately one per 300 patients – most large referral centres are likely to encounter the difficult situation of BNAO at least once a year, the paper says.

It found that despite limited evidence for efficacy, numerous therapeutic strategies had been used, inconsistently, with the 34 patients. Proton pump inhibitors (used to reduce stomach acid production and the risk of further bleeding from stress ulcers) were the most frequent blood loss minimising technique used, administered in two-thirds of the patients.

Oral iron was given in 62% of cases, whilst six patients (46%) received the blood-loss prevention medication tranexamic acid and five (38%) received erythropoietin, a hormone stimulating the production of red blood cells. Other strategies used to reduce blood loss included administering vitamins and hormones, autotransfusion and keeping the patient flat and still.

“On the one hand, they were fairly safe, cheap interventions,” first author Dr Alexander Olaussen said. “There’s not a lot of evidence for their support – that they can work – but there’s not a lot of evidence that they cause harm either,” he said.

Overall, there were three deaths in the study; one in the group of patients who became anaemic and two amongst the non-anaemic patients.

The paper’s last author Professor Biswadev Mitra, the NTRI’s Head of Clinical Research, said that multi-modal management principles are likely to be required in such patients and clinicians should be aware of all the strategies available.

“The use of HBOC (synthetic blood) is still novel and requires robust research before consideration into routine clinical practice,” Professor Mitra said.

Two patients received HBOCs. The first case made headlines in Melbourne in 2011 after a critically injured 33-year-old woman experiencing severe blood loss and who was perilously close to heart failure received HBOC-201TM flown in from the US. The other patient received SanguinateTM as part of a phase 2 research trial. Both patients survived.

HBOC contains a molecule derived from cow's blood that restores the level of haemoglobin in blood and, unlike donated blood, does not require cross-matching. Used in the US, it was introduced to The Alfred by Director of Trauma Services and study author Professor Mark Fitzgerald.

Dr Olaussen said that while the study focused on patients who were Jehovah’s Witnesses, that HBOC and findings of the study had much wider potential. HBOC can be stored without refrigeration for up to three years making it suitable for rural or remote settings in Australia, in developing countries where donor blood is not available, or on the battlefield.

“Ideally they could be given in ambulances,” Dr Olaussen said. “It would have to be studied initially from a safety point of view and to see if it could be given quickly.”

The study highlighted several important clinical points.

Clinicians needed to be aware, for instance, of the potential for critical anaemia to manifest several days after injury and the delayed haemoglobin response to non-blood treatments, leaving the patient at risk of complications from anaemia for a longer time compared to patients in whom blood transfusion is practised. It noted that the haemoglobin concentration dropped to its lowest level about four days after injury and returned to a peak concentration around two weeks.

It was also vital to take careful and deliberate consent regarding each product available when dealing with Jehovah’s Witness patients, rather than assuming refusal of blood means refusal of all products.

The study pointed out that many theoretical and biologically plausible options existed but were inconsistently practised or not used because clinicians were unaware of them.

It called for the identification of the most effective combination of strategies, followed by larger scale studies both in and out-of-hospital to better guide management of BNAO. It also recommended that an international resource centre be established to assist clinicians facing anaemia and BNAO.

Olaussen A, Bade-Boon J, Fitzgerald MC, Mitra B. Management of injured patients who were Jehovah's Witnesses, where blood transfusion may not be an option: a retrospective review. Vox Sang. 2018 Apr;113(3):283-289. doi: 10.1111/vox.12637. Epub 2018 Feb 2.

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