Dabigatran Reversal Research Articles

Idarucizumab Reversal of Dabigatran in Patients with Acute Ischemic Stroke and Intracranial Hemorrhage: Comparison with Non-idarucizumab-Treated Patients

Idarucizumab reverses the anticoagulant dabigatran; it is recommended during intravenous thrombolysis treatment of dabigatran-treated patients with acute ischemic stroke (AIS) and in dabigatran-treated patients with intracranial hemorrhage (ICH). Outcomes of consecutive idarucizumab/dabigatran-treated patients with intravenous thrombolysis-treated AIS (n = 22) were compared with consecutive similar intravenous thrombolysis-treated patients with AIS who were not anticoagulated (n = 182) [primary aim]; idarucizumab/dabigatran-treated patients with ICH (n = 13) were compared with patients with ICH who received the anticoagulants rivaroxaban or apixaban (n = 24) [secondary aim]. Efficacy was estimated by National Institutes of Health Stroke Scale score changes between admission and discharge and by the modified Rankin score after 3 months; safety was assessed by symptomatic ICH and mortality. Basal neurological impairment was similar in both idarucizumab/dabigatran-treated and control groups of patients with AIS and ICH. The idarucizumab/dabigatran-treated patients with AIS with subsequent intravenous thrombolysis showed a mean National Institutes of Health Stroke Scale improvement of 84% vs 68% in the control group (p < 0.05). A favorable outcome (modified Rankin score ≤ 2 after 3 months) was achieved significantly more frequently than in the control group (86% vs 57%; p < 0.05). The complication rate was similar in both groups. In patients with ICH, a positive functional outcome (modified Rankin score ≤ 3 after 3 months) was achieved more often in the idarucizumab/dabigatran-treated group than in the control group (70% vs 42%; p = 0.109). The complication rate was similar. Idarucizumab use in dabigatran-treated patients with AIS resulted in significantly more efficacious intravenous thrombolysis treatment and a non-significantly better outcome in dabigatran-treated patients with ICH compared with controls. There was no difference regarding complications.

Acute revascularization for ischemic stroke after reversal of dabigatran with idarucizumab: 2 case reports

要旨：【はじめに】脳梗塞急性期の治療で，rt-PA投与と血栓回収術は確立された治療だが，抗凝固薬内服中の患者に関しては十分な安全性が確立していない．今回，ダビガトラン内服中の急性期脳梗塞患者に対し，イダルシズマブ投与後にrt-PA投与と血栓回収術を行い，幸いにも良好な転帰を得た2例を経験したので報告する．【症例】（1）74歳男性．失語症状にて発症，左MCAの閉塞を認めた．Afでダビガトランを内服中．拮抗薬投与後にrt-PA静注，血栓回収術を施行した．術後CTで少量の出血性梗塞を認めたが増大なく経過．（2）89歳女性．左上下肢麻痺で発症．Afでダビガトラン内服中．左MCAの閉塞に対し拮抗薬投与した後，rt-PA静注，血栓回収術を行った．術後CTで出血なく経過した．【まとめ】ダビガトラン内服中患者の急性期脳梗塞に対して，拮抗薬投与後にrt-PA静注療法および血栓回収術を安全に施行することができた2例を報告した．

Real world use of idarucizumab for dabigatran reversal in Aragón (Spain)

Real world use of idarucizumab for dabigatran reversal in Aragón (Spain)

Dabigatran Level Before Reversal Can Predict Hemostatic Effectiveness of Idarucizumab in a Real-World Setting.

Background: Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The aim of the study was to assess the prognostic value of dabigatran plasma level before reversal to test the hemostatic efficacy of idarucizumab. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption.Methods and Results: This was an observational multicentric cohort study, which included all French patients who required idarucizumab for dabigatran reversal. Between May 2016 and April 2019, 87 patients from 21 French centers were enrolled. Patients received idarucizumab for overt bleeding (n = 61), urgent procedures (n = 24), or overdose without bleeding (n = 2). Among patients with major bleeding (n = 57), treatment with idarucizumab was considered effective in 44 (77.2%) of them. Patients who did not achieve effective hemostasis after reversal had a significantly higher mean level of plasma dabigatran at baseline (524.5 ± 386 vs. 252.8 ng/mL ± 235, p = 0.033). Furthermore, patients who did not achieve effective hemostasis after reversal had less favorable outcomes during follow-up (46.2 vs. 81.8%, p = 0.027). ROC curve identified a cutoff of 264 ng/mL for dabigatran level at admission to be predictive of ineffective hemostasis. No plasma dabigatran rebound was observed after reversal in patients with dabigatran plasma level < 264 ng/mL at baseline.Conclusion: This retrospective study shows that dabigatran level before reversal could predict hemostatic effectiveness and dabigatran plasma rebound after idarucizumab injection.

Dabigatran reversal with idarucizumab prior to lung transplantation.

When the transplant candidates are receiving oral anticoagulation therapy before transplantation, it is crucial to have an urgent reversal strategy to prevent hemorrhagic complications perioperatively. The aim of this study was to present the experience with idarucizumab to reverse the anticoagulant activity of dabigatran prior to lung transplantation. A single-center retrospective study was performed to analyze the clinical outcomes of idarucizumab use before lung transplantation. Between July 2016 and June 2019, six patients were on dabigatran at the time of transplantation. Out of the six patients, four patients received idarucizumab. These four recipients received a median of 3 units (range 0-4 units) of packed red blood cells (pRBCs) and 450ml (range 250-1500ml) of intraoperative salvage of shed blood (cell saver blood) during the lung transplant. The two patients who were not administered idarucizumab received 5 units and 13 units of pRBCs and 900ml and 3600ml of cell saver blood, respectively. There was no grade 3 primary graft dysfunction (PGD) at 72hours after transplantation or in-hospital mortality in idarucizumab group. In the group without idarucizumab, there was one case of grade 3 PGD without any in-hospital mortality. Dabigatran reversal with idarucizumab provides reasonable hemostasis during lung transplantation.

Successful intravenous thrombolysis in a patient with ischemic stroke, after reversal of Dabigatran with Idarucizumab – A case report

There remains a risk of ischemic strokes in patients of atrial fibrillation receiving oral anticoagulants. Systemic thrombolysis in such cases poses a challenge, but may be possible after reversal of anticoagulant effect. We report a case of 61-year old male patient with non-valvular atrial fibrillation who was taking dabigatran. The patient developed ischemic stroke few hours after taking the last dose of the anticoagulant. Reversal of dabigatran was achieved using idarucizumab, and the patient was successfully thrombolysed. This case-report adds to the growing evidence that such a strategy is now possible with the advent of reversal agents against non-vitamin K antagonist oral anticoagulants. Keywords: Stroke, Dabigatran, Idarucizumab, Reversal.

Real-world experience with reversal of dabigatran by idarucizumab

AimsIdarucizumab reverses the anticoagulant effect of dabigatran. We aimed to investigate real-world experience with idarucizumab and associated clinical outcomes. MethodsWe conducted a retrospective observational case series on dabigatran users treated with idarucizumab. Using electronic patient records, we identified patients from December 2015 (market introduction) to 31 December 2019 from the Central Denmark Region, covering approximately 1.3 million inhabitants. Treatment indications included need of acute surgery, major bleeding, dabigatran intoxication and need of thrombolysis. Outcomes were defined according to treatment indication, and adverse events were defined as bleeding, thrombosis or death within 30 days of infusion. ResultsA total of 46 dabigatran users were treated with idarucizumab. All patients except one received dabigatran due to atrial fibrillation. Indications for idarucizumab use were need of acute surgery in 22 (48%), severe bleeding in 20 (43%), dabigatran intoxication in three (7%), and prior to thrombolysis in acute stroke in one (2%) patient. There were no reports of excessive bleeding during surgery in patients reversed just prior to surgery. For patients presenting with severe bleeding, all but one achieved effective haemostasis. Among all patients receiving idarucizumab, six (13%) experienced bleeding within 30 days after infusion. None experienced thromboembolic complications. At 30 days follow-up, 38 (83%) patients were alive of whom 35 (92%) had restarted anticoagulant treatment. ConclusionThis study of real-world application of idarucizumab demonstrated effectiveness in terms of surgery performed without excessive bleeding and cessation of severe bleeding in dabigatran-treated patients. Safety appeared high as no patients experienced thromboembolic complications within 30 days.

Clinical outcomes after reversal of dabigatran in daily practice: real-world use of idarucizumab 2015–2019

Abstract Background Idarucizumab was introduced in Europe in December 2015 as an antidote to dabigatran. Whether reversing the anticoagulant effect of dabigatran actually reduces the risk of bleeding complications and mortality remains sparsely described. No randomized placebo-controlled trial evaluating the efficacy of idarucizumab has been conducted. Therefore, evaluation of real-world data is of major importance to further investigate the use of idarucizumab in daily clinical practice. Purpose We aimed to investigate the real-world use of idarucizumab and associated clinical outcomes. Methods The study was conducted as an observational case series. Using our regional electronic patient record, all patients treated with idarucizumab from market introduction to end of 2019 were identified. We had complete coverage of the use of idarucizumab at a large University Hospital in Denmark. During Spring 2020, we will also include patients from regional hospitals. Results A total of 39 patients were treated with idarucizumab. All patients but one received dabigatran due to atrial fibrillation. Indications for idarucizumab use were “need for acute surgery” in 21 (54%), “bleeding” in 14 (36%), “prior to thrombolysis” in two (5%), and “dabigatran intoxication” due to renal failure in two (5%, one presenting with bleeding and one patient without). No patients were treated with activated carbon or dialysis. A total of five patients (13%) experienced bleeding within 30 days after infusion and none had thromboembolic complications. After 30 days follow-up, 32 (82%) patients were alive and 29 restarted anticoagulant treatment (19 lowmolecular-weight heparin, 11 dabigatran, one rivaroxaban, and one apixaban). Conclusion Among patients treated with idarucizumab, few experienced adverse outcomes and the 30-day survival rate was high. In line with observations from the REVERSE-AD trial, our data supports that idarucizumab is safe in patients experiencing life-threatening bleeding or needing acute surgery. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted research grant from Boehringer Ingelheim

Idarucizumab for Urgent Dabigatran Reversal in Clinical Practice: A Case Series of First Use in Vietnam

The benefits of non-Vitamin K oral antagonists in prevention or treatment of thrombosis have been studied in many randomized control trials. However, episodes of life-threatening bleeding caused by using novel oral anticoagulants have occurred in clinical practice and necessitate the development of aims for reversal of the anticoagulant effects. We report here three cases in which the use of idarucizumab, a humanized monoclonal antibody fragment, has successfully reversed the anticoagulation effects of dabigatran and produced favorable outcomes.

Spotlight on the May 12 issue

#### Notable in Neurology this week This issue features an article that investigates the differences in prevalence of depression after stroke between men and women; another, using network methods, determines that the way foods are consumed, not just the quantity, may be applicable for dementia prevention. A featured article examines whether surrogates for patients with severe acute brain injury can be identified based on a survey of their prioritization of goals-of-care decisional concerns. ### Stroke reperfusion therapy following dabigatran reversal with idarucizumab in a national cohort Recent use of anticoagulants is a contraindication for the use of IV …

How Do I Reverse Oral and Parenteral Anticoagulants?

An understanding of reversal strategies alone is important to safely and effectively care for patients in cases of bleeding or invasive procedures. The recent diversification in the number of licensed anticoagulants makes an understanding of drug-specific reversal strategies essential. Intravenous or oral vitamin K can reverse the effect of vitamin K antagonists (VKAs) within 12 to 48 hours and is indicated for any bleeding or an international normalized ratio >10 or 4.5 to 10 in patients with additional risk factors for bleeding. Furthermore, an additional administration of prothrombin complex concentrate (PCC) may be necessary in cases of major bleeding related to VKA. Protamine (chloride or sulfate) fully reverses the effect of unfractionated heparin and partially in low-molecular-weight heparin. Idarucizumab has been approved for dabigatran reversal, whereas andexanet alfa is approved for the reversal of some oral factor Xa inhibitors (apixaban, rivaroxaban). PCC seems to enhance the haemostatic potential for the reversal of the effect of FXa-inhibitors. So far, there are promising but only limited data on the efficacy of this approach available. Each reversal strategy needs an adequate management beyond the hemostatic treatment (volume replacement, stabilization of homeostasis, e.g., pH and temperature, resumption of anticoagulation after successful treatment of bleeding, etc.) that is crucial for the successful management of acute bleedings, urgent high-risk surgery, thrombolytic therapies or thrombectomies as well as overdosing of anticoagulants.

Emergencies on direct oral anticoagulants: Management, outcomes, and laboratory effects of prothrombin complex concentrate

BackgroundIn the initial absence of specific reversal agents for factor Xa inhibitors (FXa‐Is), prothrombin complex concentrate (PCC) as a hemostatic agent has been recommended by guidelines. Since 2017, idarucizumab has been registered for dabigatran reversal. Still, data on the clinical outcome of direct oral anticoagulant (DOAC)‐related emergencies (major bleeding or urgent interventions) is scarce. In addition, it is unknown to what extent PCC restores thrombin generation in FXa‐I–related emergencies. Our aim was to describe management and clinical outcomes of DOAC‐related emergencies and to assess the laboratory effect of PCC in patients with FXa‐I emergencies. MethodsIn this prospective cohort study in 5 Dutch hospitals, patients presenting with DOAC‐related emergencies were eligible. The primary outcome was effective hemostasis according to the ISTH definition. Safety outcomes were 30‐day mortality and thromboembolic rate. In patients treated with PCC, additional blood samples were taken to assess the effect on thrombin generation. ResultsWe included 101 patients with major bleeding (FXa‐I, 76; dabigatran, 25) and 21 patients requiring an urgent intervention (FXa‐I, 16; dabigatran, 5). Of patients with major bleeding, 67% were treated with PCC or idarucizumab. Effective hemostasis, 30‐day mortality, and thromboembolism rate were 67%, 22%, and 1%, respectively. In a subset of bleeding patients on FXa‐I managed with PCC, thrombin generation increased, with 96% immediately after PCC administration. In patients requiring an urgent intervention, effective hemostasis, 30‐day mortality, and thromboembolic rate were 95%, 14%, and 5%. ConclusionsEffective hemostasis was achieved in the majority of patients presenting with DOAC‐related emergencies;, thromboembolic complications were rare, and mortality was quite high.

Dabigatran Reversal Before Intravenous Tenecteplase in Acute Ischemic Stroke.

Background and Purpose- Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods- We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results- We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69-85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4-21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57-113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0-2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions- Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.

Idarucizumab for dabigatran reversal in daily clinical practice

Real-life experience with idarucizumab, which reverses the anticoagulant effect of dabigatran, is currently limited. To evaluate efficacy and safety of the clinical use of idarucizumab after its availability in Slovenia. We analysed consecutive cases treated with idarucizumab in Slovenia from January to October 2016. The decision to reverse dabigatran with idarucizumab was made by the treating clinicians, as was the assessment of clinical outcomes and blood sampling/monitoring (activated partial thromboplastin time, thrombin time and diluted thrombin time) before and after use. Idarucizumab was used in 17 cases. One patient was treated with the antidote twice with an interval of 2 months between treatments. The indications for idarucizumab use were: emergency surgery (4/17), severe bleeding (11/17; seven with intracranial bleeding) and ischaemic stroke (2/17). During surgery, no excessive bleeding was reported. Five patients died due to cardiogenic, haemorrhagic or septic shock, intracranial bleeding or multiple organ failure. Among cases with laboratory data available, baseline coagulation tests were prolonged in 12/13 cases with bleeding or emergency surgery. After idarucizumab administration, normal coagulation parameters were confirmed in 10/11. However, re-occurrence of dabigatran effect was noted later in four patients with creatinine clearance less than 30 ml min, and one patient with persistent bleeding required retreatment with idarucizumab. Our first experiences with idarucizumab use in daily-care settings support a rapid and efficient decrease in the anticoagulant effect of dabigatran in emergency situations. Late re-occurrence of dabigatran effect was noted in a subset of patients with severe renal failure.

Idarucizumab for Emergency Reversal of Anticoagulant Effects of Dabigatran: Interim Results of a Japanese Post-Marketing Surveillance Study.

IntroductionIdarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran, and it was approved in Japan in September 2016. An all-case post-marketing surveillance is ongoing to collect data in Japanese patients treated with idarucizumab who had serious bleeding (Group A) or required an urgent procedure (Group B).MethodsThe primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effect of dabigatran based on activated partial thromboplastin time (aPTT) within 4 h after idarucizumab administration.ResultsThis interim analysis included 262 patients who received idarucizumab. Eighteen patients (6.9%) experienced ADRs within 4 weeks. The reversal effect of idarucizumab based on aPTT within 4 h after idarucizumab administration was assessed in 30 patients and the median maximum percentage reversal was 100%. In Group A, the median time to bleeding cessation in patients without intracranial bleeding was 3.3 h. In Group B, normal intraoperative hemostasis was reported in 63 patients (72.4%).ConclusionsThe results of this interim analysis suggest that idarucizumab is safe and effective for the reversal of dabigatran in Japanese patients in a real-world setting, and support the continued use of idarucizumab.Trial RegistrationClinicalTrials.gov identifier, NCT02946931. Video Electronic supplementary materialThe online version of this article (10.1007/s40119-020-00165-8) contains supplementary material, which is available to authorized users.

Stroke reperfusion therapy following dabigatran reversal with idarucizumab in a national cohort.

To assess the frequency and utilization trends of dabigatran reversal with idarucizumab and compare associated complications, outcomes, and door-to-needle times to those of patients not exposed to idarucizumab in a nationwide cohort of thrombolyzed patients over a 24-month period. This is an observational cohort study of all New Zealand patients with stroke treated with stroke reperfusion entered into a mandatory online national registry. Each hospital records data including patient demographics, treatment delays, complications, 7-day outcomes, and idarucizumab use. Between 1 January 2017 and 31 December 2018, 1,336 patients received thrombolysis. Fifty-one patients received idarucizumab prior to thrombolysis (median [interquartile range] age 73 [57-83] years): 8 (1.3%) in 2017 and 43 (6%) in 2018 (p < 0.001). Over the same 24-month period, 386 patients had stroke clot retrieval, of whom 8 (2.1%) were first treated with idarucizumab. Idarucizumab-treated patients had slower door-to-needle times (83 [54-110] minutes vs 61 [43-85] minutes, p = 0.0006). Symptomatic intracerebral hemorrhage occurred in 2 (3.9%) of the idarucizumab-treated patients and 49 (3.8%) of the other thrombolyzed patients (p = 0.97). None of the idarucizumab-treated patients had significant thrombotic complications. At 7 days, 3 (5.9%) idarucizumab-treated and 101 (7.9%) of the other thrombolyzed patients had died (p = 0.61). Idarucizumab was used in 6% of all thrombolyzed patients in a national cohort during 2018, up from 1.3% in 2017. Idarucizumab appeared to be safe with similar clinical outcomes to routinely managed patients, despite a 22-minute door-to-needle time delay. Idarucizumab can facilitate thrombolysis in patients with stroke taking dabigatran. This study provides Class III evidence that idarucizumab use is associated with similar early post-thrombolysis outcomes compared with patients not exposed to this drug.

Effective Removal of Dabigatran by Idarucizumab or Hemodialysis: A Physiologically Based Pharmacokinetic Modeling Analysis.

BackgroundApplication of idarucizumab and hemodialysis are options to reverse the action of the oral anticoagulant dabigatran in emergency situations.ObjectivesThe objectives of this study were to build and evaluate a mechanistic, whole-body physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of idarucizumab, including its effects on dabigatran plasma concentrations and blood coagulation, in healthy and renally impaired individuals, and to include the effect of hemodialysis on dabigatran exposure.MethodsThe idarucizumab model was built with the software packages PK-Sim® and MoBi® and evaluated using the full range of available clinical data. The default kidney structure in MoBi® was extended to mechanistically describe the renal reabsorption of idarucizumab and to correctly reproduce the reported fractions excreted into urine. To model the PD effects of idarucizumab on dabigatran plasma concentrations, and consequently also on blood coagulation, idarucizumab-dabigatran binding was implemented and a previously established PBPK model of dabigatran was expanded to a PBPK/PD model. The effect of hemodialysis on dabigatran was implemented by the addition of an extracorporeal dialyzer compartment with a clearance process governed by dialysate and blood flow rates.ResultsThe established idarucizumab-dabigatran-hemodialysis PBPK/PD model shows a good descriptive and predictive performance. To capture the clinical data of patients with renal impairment, both glomerular filtration and tubular reabsorption were modeled as functions of the individual creatinine clearance.ConclusionsA comprehensive and mechanistic PBPK/PD model to study dabigatran reversal has been established, which includes whole-body PBPK modeling of idarucizumab, the idarucizumab-dabigatran interaction, dabigatran hemodialysis, the pharmacodynamic effect of dabigatran on blood coagulation, and the impact of renal function in these different scenarios. The model was applied to explore different reversal scenarios for dabigatran therapy.Electronic supplementary materialThe online version of this article (10.1007/s40262-019-00857-y) contains supplementary material, which is available to authorized users.

Whole Blood Point-of-Care Testing for Incomplete Reversal With Idarucizumab in Supratherapeutic Dabigatran.

Incomplete reversal with a recommended 5-g dose of idarucizumab has been reported in patients with excessively high dabigatran concentrations. A timely detection of reversal failure after idarucizumab using whole blood (WB) coagulation testing is clinically useful. The aims of this study were to determine residual dabigatran activity after idarucizumab on thrombin generation (TG) using in vitro supratherapeutic dabigatran models and to compare 4 WB point-of-care tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and 2 thromboelastometry tests) with the TG results. Blood samples from 12 healthy volunteers were spiked in vitro with 0-5000 ng/mL of dabigatran. Dabigatran reversal was evaluated by adding 1000 μg/mL of idarucizumab (Praxbind) to dabigatran-spiked samples, which reflect the administration of 5-g idarucizumab to a 70-kg patient. Residual dabigatran activity was assessed using the calibrated automated TG (Thrombinoscope) in platelet-poor plasma samples. The TG results were compared with WB aPTT (DRIHEMATO APTT-S) and PT (DRIHEMATO PT-S) using CG02N analyzer, thromboelastometry (ROTEM) triggered by ellagic acid (INTEM) and tissue factor (EXTEM). At a therapeutic concentration of dabigatran (200 ng/mL), the lag time was prolonged, and peak TG was decreased. The effects of dabigatran on TG were increased up to 1000 ng/mL, and TG was obliterated at higher supratherapeutic dabigatran levels (P < .001 versus control, respectively). TG was fully restored with idarucizumab when dabigatran was ≤2000 ng/mL, but residual anticoagulant activity was observed at higher dabigatran levels. Dabigatran prolonged WB aPTT and PT concentration dependently, and residual prolongations were observed when idarucizumab was added to 3000 or 5000 ng/mL of dabigatran (P < .001 versus control, respectively). In contrast, both INTEM and EXTEM clotting times were reversed toward reference ranges at all dabigatran concentrations when idarucizumab was added. Our data indicate that the recommended dose of idarucizumab may not restore TG completely with excessively elevated concentrations of dabigatran. All WB measurements with aPTT, PT, and thromboelastometry predicted supratherapeutic dabigatran concentrations, whereas those tests varied in sensitivity to residual anticoagulant activity after reversal. WB aPTT corresponded well with plasma TG changes among those measurements, but the use of thromboelastometry may overestimate the effect of idarucizumab. Caution should be exercised before extrapolating in vitro point-of-care data to the clinical monitoring of dabigatran reversal.

Abstract WP118: Laboratory Examinations - Lessons Learned From 120 Cases Treated With Idarucizumab in Germany

Recently we have shown that idarucizumab application in acute stroke patients treated with dabigatran improves clinical outcome parameters. In this retrospective series of 120 cases positive effects of dabigatran reversal could be documented regarding mortality and modified Rankin scale in patients with acute hemorrhagic stroke (ICH). At the same time, individuals with acute ischemic stroke (IS) regained eligibiliy for intravenous thrombolysis, thereby improving substantially in NIHSS. Here, we report results on medication and blood parameters from this case series. In acute ICH, 15 of 40 patients were on dabigatran 150mg bid, while 25 took 110mg bid. CrCl was above 50ml/min in all cases while TT upon admission was elevated substantially in almost all cases examined. aPTT was normal in 79.5%. In acute IS, 32 patients received 150 mg, 48 received 110 mg dabigatran bid. The vast majority of patients with ischemic stroke had a CrCl above 50 ml/min. TT was prolonged above 35 seconds in 91.4% of cases while aPTT values were normal in 48.1% of patients. These data underline the necessity to prescribe the appropriate dosage recommended in the prescription protocol to all patients since ICH and IS incidence seems to be dose-independent. Furthermore, global hemostasis parameters like aPTT again prove to be not useful for therapeutic decisions. Finally, inclusion of TT values into emergency laboratory examination in patients with acute stroke under dabigatran is helpful to identify patients with impaired hemostasis potentially benefitting from idarucizumab application.

Idarucizumab for dabigatran reversal in the patient with subarachnoid hemorrhage

Idarucizumab for dabigatran reversal in the patient with subarachnoid hemorrhage