Coronial
VIChospital

Finding into death of Kathryn Maree Jelbart

Deceased

Kathryn Maree Jelbart

Demographics

59y, female

Date of death

2016-03-25

Finding date

2018-01-18

Cause of death

Multiorgan failure and polymicrobial sepsis secondary to severe bone marrow failure due to azathioprine toxicity in setting of TPMT genetic polymorphism

AI-generated summary

A 59-year-old woman with renal transplant died from multiorgan failure and sepsis secondary to severe bone marrow failure caused by azathioprine toxicity. She had an undiagnosed genetic polymorphism (TPMT *3A/*3A homozygous) causing extreme sensitivity to azathioprine's myelosuppressive effects. Azathioprine was substituted for mycophenolate overseas and continued despite subsequent bone marrow suppression. The critical clinical lesson is that TPMT genotyping should be mandatory before prescribing thiopurine-containing medications. The death was preventable through pre-treatment genetic testing, which would have identified her extreme risk and allowed therapeutic alternatives or drastically reduced dosing. This case identified a significant gap in clinical practice that led to policy change at the treating institution.

AI-generated summary and tagging — may contain inaccuracies; refer to original finding for legal purposes.

Specialties

nephrologytransplant medicineintensive carehaematologyinfectious diseases

Error types

diagnosticsystem

Drugs involved

azathioprinemycophenolateprednisolonetacrolimusfilgrastim

Clinical conditions

azathioprine toxicitybone marrow failurepancytopeniamyelosuppressionpolymicrobial sepsismulti-organ failureTPMT genetic polymorphismrenal transplantspina bifidadeep venous thrombosishepatitis bsupraventricular tachycardia

Procedures

renal transplantation

Contributing factors

  • Absence of TPMT genetic testing prior to azathioprine prescription
  • Undiagnosed genetic susceptibility to azathioprine (TPMT *3A/*3A homozygous)
  • Substitution of mycophenolate with azathioprine without genetic testing
  • Continuation of azathioprine despite development of pancytopenia and bone marrow suppression
  • Lack of clinical guideline for mandatory TPMT testing in Australia at time
  • Lack of prescriber knowledge regarding TPMT testing availability and importance

Coroner's recommendations

  1. TPMT genotyping for common alleles should be mandatory for patients prior to commencement of thiopurine-containing medications
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