Cholestatic liver injury as a side-effect of dabigatran and the use of coagulation tests in dabigatran intoxication and after reversal by idarucizumab in bleeding and sepsis

Abstract

Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure. INR and APTT can be elevated if sepsis is complicated by disseminated intravascular coagulation (DIC) or liver failure, making it challenging to determine dabigatrans contribution to their prolongation. A rebound effect after administration of idarucizumab and slow elimination of dabigatran due to reduced kidney function could be detected using the Hemoclot diluted thrombin time (dTT) in this situation, in contrast to with non-dilutional assays. Before admission, cholestatic liver injury started shortly after initiation of dabigatran etexilate therapy. As no other cause was found, this liver injury was likely to be drug-induced. Bleeding cessated promptly after administration of idarucizumab in dabigatran intoxication. In conclusion, the anticoagulant effect of dabigatran can be measured by Hemoclot dTT in sepsis and cholestatic liver injury was seen as a possible rare side-effect of dabigatran treatment.

Assessment of thiol/disulfide balance as an oxidative stress marker in children with β-thalassemia major

“…The other advantages of this method are that it is inexpensive, practical, simple, rapid, and suitable for routine use 10. Recent studies have reported that impaired TDB is associated with various disorders such as diabetes mellitus11, myocardial infarction12, familial Mediterranean fever13, and cancer 14. However, to our knowledge, TDB as an index of oxidative stress in children with β-TM has not been investigated by using a newly developed method.…”

Case series of massive direct oral anticoagulant ingestion—Treatment and pharmacokinetics data

“…Overdose resulting from DOAC self‐ingestion has been poorly reported, mostly as single cases, limited series and PCC reports, representing ~100 cases, with serum/plasma concentration assessment in <20 cases (Table 3). 12–35 Overall, suicidal ingestion does not seem to result in notable bleeding despite high‐ingested amounts and high peak plasma concentrations in most patients. Of note, peak DOAC concentrations in patients included in clinical trials evaluating DOAC for stroke prevention in atrial fibrillation or venous thromboembolism treatment (ie at regular doses) showed a wide inter‐individual variability 3,36 .…”

“…Overall, 29 additional cases mostly involving intentional exposure to dabigatran ( n = 15), rivaroxaban ( n = 8) and apixaban ( n = 6) were published (Table 3). 12–35 Only 10 of these 29 cases presented bleeding. A 53‐year‐old man who co‐ingested 200 mg apixaban presented minor oozing from his femoral venous line insertion site, easily controlled with direct pressure and prothrombin complex concentrate 13 .…”

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation

“…In addition, the peak value of anti-FIIa was significantly correlated with bleeding events, indicating that anti-FIIa activity is more worthy of clinical attention than the other PD indicators. Relevant studies also showed that patients with high peak values of PD indicators such as APTT experienced significantly more bleeding events ( 30 ). Nevertheless, the trough value is more related to the bleeding risk than the peak value ( 31 ).…”