Extracorporeal removal techniques in toxicology: part 1.

Supporting clearance of a toxic substance by an extracorporeal removal technique is one of the advanced treatment methods applied in poisoned patient management. General indications stem from toxicokinetics of the poison while individual indications are determined by poisoning severity. The first part of this review deals in detail with particular options of extracorporeal treatment in toxicology and also with its specific application when treating lithium and salicylates poisoning or dabigatran overdose. The aim of this review is to facilitate the clinicians and nephrologists decision making whether to indicate this invasive procedure, to communicate and summarize the existing recommendations and to highlight the most important ways of how to treat poisoning by specific toxic substances.

[Successful treatment of severe dabigatran intoxication with idarucizumab in a patient with acute kidney injury].

In the course of an uncomplicated sigmoidostomy a 63-year-old male who had severe comorbidity developed a critical bleeding due to dabigatran intoxication induced by acute kidney injury. Massive blood transfusions, tranexamic acid, Octaplex and haemodialysis were not effective. Administration of idarucizumab induced immediate clinical and paraclinical improvement. Dabigatran should be carefully administrated in patients who have any degree of renal insufficiency. Idarucizumab may be effective in severe bleeding caused by dabigatran.

Idarucizumab for dabigatran overdose.

CONTEXT: An overdose of oral anticoagulants represents a challenging scenario for emergency physicians. Dabigatran, an oral direct thrombin inhibitor, is increasingly used in place of warfarin. The lack of an antidote is a concern in patients who overdose on dabigatran, even though the drug can be eliminated with hemodialysis. Idarucizumab is an antibody fragment that binds dabigatran with high affinity. It reverses the anticoagulant effect of dabigatran within minutes and is approved for the reversal of dabigatran during emergency situations. CASE DETAILS: We describe the use of idarucizumab in the management of a 68-year-old woman who was taking dabigatran 150 mg twice daily and ingested 125 capsules. Despite gastric lavage and administration of activated charcoal within two hours of drug intake, the activated partial thromboplastin time (aPTT) and prothrombin time (PT) remained prolonged. The administration of 5 g of intravenous idarucizumab promptly and completely reversed the anticoagulant activity of dabigatran as assessed by routine and specific coagulation assays (aPTT from to 75 to 26 s, PT from 26 to 11 s and diluted thrombin time from 92 to 27 s). The initially planned emergency hemodialysis was canceled. DISCUSSION: This case highlights the potential use of idarucizumab for the management of massive dabigatran overdoses.

Dabigatran deliberate overdose: two cases and suggestions for laboratory monitoring.

CONTEXT: Dabigatran etexilate (dabigatran) is a direct thrombin inhibitor anticoagulant agent. There is limited information about the changes in coagulation profile and outcomes in overdose. A monoclonal antibody has been developed to neutralize the anticoagulant effect of dabigatran. Case reports describe enhanced clearance of dabigatran by haemodialysis as an intervention to prevent haemorrhagic complications - however, the threshold for initiating haemodialysis is not well defined in an asymptomatic patient with normal renal function. CASE DETAILS: Two patients presented following deliberate dabigatran overdoses. A 55-year-old woman ingested 10 × 150 mg dabigatran. A 21-year-old woman with a history of systemic lupus erythematosus and pulmonary embolus ingested 100 × 110 mg dabigatran. Both were admitted to the intensive care unit and managed expectantly. Serial coagulation tests normalized over 60 h. The half-life of dabigatran was not prolonged following overdose, being calculated between 7 and 11 h in each case. There was positive correlation between international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (aPTT) with plasma dabigatran levels. CONCLUSION: There is limited experience with dabigatran overdoses. Normal aPTT, PT and INR assays 12 h following deliberate ingestion indicate that the drug concentration is not high. Individual risk assessment of bleeding risk needs to be formulated for each patient and expectant management is reasonable in the presence of normal renal function and absent risk factors for bleeding.

Enhanced elimination of dabigatran through extracorporeal methods.

Several pharmacokinetic studies have suggested that dabigatran possesses a number of ideal properties for expedited removal via extracorporeal methods. However, this practice has not been prospectively evaluated in patients with life-threatening bleeding or requiring emergency surgery secondary to dabigatran-associated coagulopathy. The purpose of this literature review is to evaluate the published evidence surrounding extracorporeal removal of dabigatran in the setting of emergency surgery or life-threatening bleeding. A query of MEDLINE, Web of Science, International Pharmaceutical Abstracts, and Google Scholar using the terms dabigatran, dabigatran etexilate, hemodialysis, renal replacement therapy, hemorrhage, and atrial fibrillation was used to retrieve relevant literature. Furthermore, a manual search of the references of the identified literature was performed to capture additional data. Current evidence suggests that extracorporeal removal of dabigatran may play a role in the setting of life-threatening bleeding and emergent surgery. Conflicting evidence exists with regard to the potential for redistribution based on serum dabigatran concentrations. In addition, a number of practicalities must be considered before incorporating this technique in the clinical setting. Extracorporeal removal of dabigatran may be a treatment modality in selected patients who require emergency reversal.

[Serious bleeding as a consequence of accumulation of dabigatran caused by renal failure].

A 77-year-old male was hospitalized due to haematuria and developed septicaemia. He received dabigatran due to chronic atrial fibrillation. Doses were reduced because of renal failure according to guidelines. The patient showed extensive changes in his entire coagulation system. Due to renal failure forced diuresis was not possible, and continuous dialysis was performed. Patients with renal failure should be monitored closely - if there are any sign of bleeding it is important to consider change of anticoagulant therapy as long as an antidote does not exist.