Download The Role Of Eculizumab In Treating A Jehovah`s Witness With Atypical

Background
Thrombotic microangiopathy (TMA) is characterised by microscopic angiopathic haemolytic
anaemia (MAHA), thrombocytopenia and organ injury. Whilst the diagnosis of TMA is based
on clinical and laboratory findings, the distinction between aetiologies is not always
immediately apparent. Atypical haemolytic uraemic syndrome (aHUS), a cause of TMA, is
associated with significant morbidity and mortality. Traditionally supportive therapy including
the use of blood products is required whilst decisions regarding targeted therapy are made,
however this is limited in patients where blood products are not allowed. Therapeutic options
for aHUS have increased recently to include the terminal complement inhibitor eculizumab
(ECU). Early treatment with ECU has improved outcome by limiting a secondary endothelial
cascade. Diagnostic uncertainty in the initial presentation of TMA can delay the delivery of
ECU as diagnostic criteria for aHUS rely on exclusion of other causes of TMA. UK guidelines
recommend the availability of results for the ADAMTS13 assay before commencing treatment.
Case description
We report the case of a twenty-three year old healthy female Australian citizen, with permanent
Canadian residency, who presented to the Accident and Emergency (A+E) department with a
seven day history of non-bloody diarrhoea and vomiting (Day 1). She was clinically stable and
discharged with a diagnosis of viral gastroenteritis. Near patient testing showed haemoglobin of
127g/L. The patient represented to the same A+E department on Day 3 with heavy vaginal
bleeding, not related to menstruation. She was haemodynamically stable, clinical examination
was unremarkable and near patient testing indicated haemoglobin 79g/L. She was transferred to
the care of the gynaecology team and treated for heavy menstrual bleeding. Laboratory bloods
taken on Day 4 indicated; haemoglobin 54g/L, platelets 34x10/L and lactic dehydrogenase
3,077. Renal functions tests showed stage 3 acute kidney injury (AKI); serum creatinine
371umol/L, and serum urea 47.4umol/L. The patient disclosed that she was a Jehovah’s Witness
and that she did not want to receive any blood products, even if her life was threatened however
she was happy to receive erythropoietin stimulating agents and intravenous iron. A diagnosis of
aHUS was considered due to the clinical presentation. The patient was transferred to the critical
care unit (CCU) on the evening of Day 4 where she commenced renal replacement therapy
(RRT). TMA screen was sent (complement 3 and 4, total complement activity (CH50),
complement genetics, anti-factor H autoantibody and ADAMTS13). Urgent discussions took
place with the UK national aHUS on-call service, which controlled the UK national funding for
ECU. Given the clinical situation and patient decision regarding blood products, a decision was
made to proceed with the administration of ECU without waiting for the ADAMTS13 activity.
The initial dose was given on Day 5. On Day 7 the patient was intubated and ventilated.
Haemoglobin dropped to its lowest value on Day 8 to 28g/L. Clinical and biochemical
improvement began thereafter. The patient was extubated on Day 13. On Day 14 the second
dose of ECU was administered and RRT was discontinued. On Day 18 the patient was
transferred to the renal ward where she remained stable. On Day 23 and Day 31 she had further
doses of ECU. She was discharged on Day 31 with a normal renal function, haemoglobin 111/L
and a platelet count of 302x10/L. The patient had a follow up appointment with a haematologist
in Canada to explore options to secure funding for further ECU treatment. Results after
discharge showed a negative TMA screen, including ADAMTS13.
Discussion
This case highlights the successful treatment of TMA caused by aHUS with the early
administration of ECU in a patient who declined blood products due to religious beliefs.
It was also associated with high healthcare costs; however ECU was not approved for use in
either country from where this patient came. This case highlights disparities in availability
between high cost medications within industrialist nations and potential heath economic issues
for patients declining ‘standard’ care therapies regardless of reasons.