LAUSR

We report the first use of idarucizumab in the management of a massive dabigatran overdose in a child. Anticoagulation overdose is a challenging clinical scenario. Dabigatran, an oral direct thrombin inhibitor, is licensed for treatment and secondary prevention of venous thromboembolism and for stroke prevention in atrial fibrillation. Idarucizumab is a humanised monoclonal high affinity antibody fragment that specifically binds to, and neutralises dabigatran. It has recently been approved by the European Medicines Agency and the US Food and Drug Administration. A 15-year-old girl presented to the emergency department following the ingestion of between thirty and fifty 150-mg dabigatran tablets 4 h previously (dabigatran prescribed for her father). She had a history of self-harm with multiple emergency department attendances and had been recently expelled from school. She had no other significant medical history, no regular medications and no known drug allergies. She had minor gum bleeding and was haemodynamically stable (weight 67 kg). Initial blood tests showed normal full blood count, renal and liver function (creatinine 46 lmol/l). The coagulation profile was abnormal with an international normalised ratio (INR) of 9 1 and an activated partial thromboplastin ratio (APTR) of 4 8. No alcohol, paracetamol or salicylate was detected. Repeat coagulation tests locally confirmed prolongation of INR and APTR, fibrinogen 2 6 g/l and thrombin time (TT) reported as 53 s. Thrombin time is the most sensitive standard coagulation test to dabigatran and is sensitive to minimum levels of dabigatran. The activated partial thromboplastin time (APTT) is sensitive to dabigratran within the normal therapeutic range, but the increase in APTT starts to plateau beyond about 200 ng/ml dabigatran. The INR is, in general, less sensitive to dabigatran than the APTT and its degree of prolongation is reagent dependent (Stangier et al, 2007; van Ryn et al, 2010). In this case, the PT and APTR were consistent with the history of dabigatran overdose but the TT was not. However the patient and her family confirmed that she had taken dabigatran, and that there were no other anticoagulants in the house. She had a normal coagulation screen from a previous emergency department attendance. As she had no significant active bleeding, and the coagulation results did not match the reported history, the decision was made to administer 10 mg/kg tranexamic acid and 10 mg vitamin K intravenously. Prothrombin complex concentrate (PCC) was to be used if the patient developed significant bleeding and idarucizumab requested (not initially on site) to be available in case of need. Blood samples were couriered to the tertiary centre. These coagulation screen results were consistent with massive dabigatran overdose, with an unclottable TT (Table I). This was confirmed by a dabigatran assay (dilute thrombin time, Hemoclot assay) (Table I, Fig 1). Under standard conditions, this assay determines dabigatran levels between 30 and 500 ng/ml, however manual dilutions estimated initial dabigatran levels to be 1507–2040 ng/ml. The therapeutic peak dabigatran levels for patients taking 150 mg twice a day in the RE-LY trial was median 184 ng/ ml (range 74 3–383 ng/ml, 10–90 percentile) (Reilly et al, 2014), and the half-life of dabigatran in patients with normal renal function is 10–13 h. Our 15-year-old patient had 5–10 times supranormal levels and it was therefore estimated that it would take approximately 48 h for dabigatran to be