dabigatran is a direct thrombin inhibitor indicated in prevention of thromboembolic disease in patients with non - valvular atrial fibrillation . contrary to vitamin k antagonists , no specific blood monitoring is recommended for dabigatran even if there is a real risk of accumulation in the case of renal impairment [ 24 ] . presently , the procedure to reverse dabigatran in the case of life - threatening bleeding or in situations where urgent surgery is required is not well formalized . it is suggested to use procoagulant drugs [ 5 , 6 ] . additionally , based on the characteristics of dabigatran ( small molecular weight of 630 da and low binding to proteins , 30% ) , previous studies have focused on removal of dabigatran using conventional haemodialysis , with good results [ 716 ] . conventional dialysis usually means a diffusive method with high blood flow ( 350 ml / min ) , arteriovenous fistula and high dialysate rate ( 500 ml / min ) . not rarely , patients with life - threatening bleeding need to be hospitalized in the intensive care unit ( icu ) where conventional techniques are not always available . furthermore , patients with massive bleeding can be haemodynamically unstable and conventional haemodialysis in this context may not be well tolerated . for these reasons , the use of convective - based renal replacement therapy ( rrt ) like haemodiafiltration ( hdf ) may have a place in the management of patients with undesirable blood concentration of dabigatran . however , very few data exist on the ability of those techniques to efficiently remove dabigatran from blood . we report here the case of a patient admitted to the icu for life - threatening bleeding in the context of dabigatran overexposure managed by hdf . a 74-year - old man was presented to the emergency department with epigastric pain , asthaenia and drowsiness . he had a past medical history of chronic heart failure , chronic subdural haematoma , atrial fibrillation and chronic kidney disease stage 3b and received dabigatran 75 mg twice daily . he was somnolent but arousable , confused with glasgow coma scale 14 , haemodynamically unstable with hypotension ( 95/51 mmhg ) , mottled skin and tachycardia ( 100 bpm ) . first biology results found anaemia with haemoglobin 7 g / dl ( versus 11.5 g / dl two weeks before ) and creatinine 276 mol / l ( versus 150 mol / l usually ) i.e. acute kidney injury stage 1 kdigo . plasma coagulation was abnormal with prothrombin ratio ( pr ) 28% and activated partial thromboplastin time ( aptt ) 66 s. blood dabigatran level was 534.9 ng / ml . brain computed tomography found chronic subdural haematoma without acute bleeding . the patient received 3 packed red blood cells and 1000 ml of intravenous fluids ( sodium chloride 0.9% ) . . continuous infusion by proton pump inhibitor was started ( omeprazole 8 mg / h ) . a dialysis catheter ( blue flextip catheter , 2 lumen , 16 cm , 12 fr - arrow ) was inserted in the right internal jugular vein . the patient was started on 4 h of hdf on prisma flex system ( gambro ) with a high - flux dialysis filter ( multiflow 60 an69hf 0.60 m polyacrylonitrile hollow - fibre membrane ) . the blood ( qb ) , dialysate ( qd ) and ultrafiltration ( quf ) flow rates were 200 ml / min , 1 l / h and 3 l / h , respectively . substitution fluids were delivered in predilution ( 1 l / h ) and in postdilution ( 2 l / h ) with zero net ultrafiltration . dabigatran levels were sampled every 20 min in blood ( inlet line ) and effluent ( ultrafiltration and dialysate volume collected every 20 min ) . diuresis was 250 ml on 8 h with residual clearance of creatinine measured at 14 ml / min . it decreased gradually during the session to reach 160.5 ng / ml after 4 h ( figure  1 ) . decrease of dabigatran during hdf was of 25% at 2 h and 51% at 4 h. conversely , the effluent level of dabigatran increased to reach 138.5 ng / ml at the end of the session . in parallel , aptt decreased from 180 s at the initiation of hdf to 57.8 s 4 h after the session and pr increased from 30 to 41% . the patient did not receive any drugs that could have interfered with clotting time . black line represents dabigatran plasma concentrations ; grey line represents dabigatran effluent concentration . plasma and effluent dabigatran during hdf session . cl(hdf ) was measured every 20 min using the recovery method according to the following equation cl(hdf ) = ev / p where e = effluent concentration of dabigatran , v = effluent rate and p = dabigatran plasma concentration . the half - life of dabigatran was 4.8 h. only the terminal half - life was determined according to the following equation t1/2 = ln(2)/lambda(z ) where lambda(z ) is the slope of the terminal portion of the log transform concentrations versus time . a rebound of concentrations of dabigatran was observed with a plasma level at 195.7 ng / ml 2 h after the end of the hdf session . six hours after the hdf session , dabigatran concentration decreases to reach 11 ng / ml probably due to renal recovery . because of renal recovery , clotting time improvement and decrease of dabigatran levels , no other dialysis session was realized . coagulation parameters continued to improve with pr 76% and aptt 37 s at the patient 's discharge . after cardiologic consultation , dabigatran was discontinued , replaced by aspirin because of a major risk of bleeding compared with the thromboembolic risk . this case report focused on the interest of convective - based rrt in dabigatran - associated bleeding . in our report , dabigatran blood level decreased from 325.3 to 160.5 ng / ml with a 4-h session of hdf equivalent to a decrease of 51% of dabigatran . dabigatran half - life during hdf session was 4.8 h. this figure has to be compared with an expected half - life of 28 h in this patient with glomerular filtration rate ( gfr ) below 30 ml / min . thus , the half - life during hdf session is < 25% of the half - life off therapy which by definition confirms that dabigatran is effectively removed by hdf . several studies have previously reported the efficacy of haemodialysis techniques to clear dabigatran in different situations . .   found an extraction coefficient of dabigatran after 4 h of conventional haemodialysis at 68% , and khadzhynov et al .   reported extractions ratios > 45% . more recently , singh et al .   published on their experience of five cases of acute bleeding associated to dabigatran . all patients received conventional haemodialysis with a decrease of dabigatran ranging from 52 to 77% . in his study , an additional rrt session because of a rebound of dabigatran concentrations was performed using continuous venovenous haemodiafiltration ( cvvhdf ) apparently with a good result but very few data are given . regarding the efficacy of convective techniques , chiew et al . reported on a 66-year - old man treated by 32 h of cvvhdf for dabigatran overdose . they found a mean extraction ratio of 0.2% and a mean dabigatran clearance of 58.1 ml / min using the recovery method . this case report is a prototype of a patient requiring intensive care , with acute bleeding due to dabigatran overdose . importantly , we provide here full pharmacokinetic analyses allowing an evaluation of key pharmacokinetic parameters ( clearance , half - life ) . decrease of dabigatran ( 51% ) is less important than when conventional dialysis is used ( 5080% ) , probably because of a low dialysate flow rate ( 1 l / h ) and the small surface area of the filter ( 0.6 square metre ) . the absence of urine samples did not allow a direct evaluation of renal clearance of dabigatran but as the patient was oliguric we believed that renal excretion of dabigatran was negligible . the difference between dabigatran levels at the admission ( 534.9 ng / ml ) and at the initiation of hdf ( 325.3 ng / ml ) has probably more to do with haemodilution than renal excretion since the patient received three packed red blood cells and 1000 ml of saline solution before the beginning of hdf . the fact that the drug was not at steady - state when dialysis was started and the large distribution volume of dabigatran ( 70% )   can explain the relative increase of blood dabigatran concentrations during hdf session . although thrombin time ( tt ) assay is the best test to assess dabigatran activity , it was not available in the emergency ward in our hospital . however , aptt can be used for a qualitative assessment of dabigatran exposure , and some authors described a good correlation between aptt and dabigatran concentrations . in conclusion , this case report suggests that hdf may be an efficient approach for dabigatran removal and can be performed in the case of unstable , critically ill patients with dabigatran overexposure .
dabigatran is a direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with non - valvular atrial fibrillation . 
 the procedure to manage dabigatran - associated haemorrhages is not well formalized . 
 conventional haemodialysis has been evaluated with good results . 
 patients with dabigatran - associated bleeding may be unstable and convective techniques like venovenous haemodiafiltration ( hdf ) can be interesting . 
 we report the case of a 74-year - old , critically ill patient with haemorrhagic shock and dabigatran overexposure due to acute kidney injury . 
 he underwent hdf and dabigatran blood concentrations decreased from 325.3 ng / ml to 160.5 ng / ml . 
 we report here key pharmacokinetics parameters ( half - life , extraction coefficient , clearance ) .