Idarucizumab for Reversing Anticoagulation in Patients Treated with Dabigatran: Experience in Our Center

INTRODUCTION

Patients who are receiving oral anticoagulant therapy for the prevention of stroke or thrombosis may benefit from anticoagulant reversal if they present life-threatening bleeding or if they will be undergoing urgent surgery or intervention.

Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds dabigatran and its metabolites with a very high affinity, approximately 300 times more potent than the binding affinity of dabigatran to thrombin. It thus neutralizes its anticoagulant effect. It is indicated in adult patients treated with this direct oral anticoagulant when a rapid reversal of its anticoagulant effect is required, for surgical or urgent procedures and in the case of potentially fatal or uncontrolled bleeding.

It is given intravenously. The recommended dose is 5 g administered in two intravenous infusions of 2.5 g every 5-10 minutes.

OBJECTIVES

This is a descriptive study to determine whether darucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who are about to undergo an urgent procedure.

METHODS

The two clinical cases of patients treated with idarucizumab in this year are described.

CASE 1

A 70-year-old woman receiving anticoagulant Dabigatran 150mg/12h for Non-valvular Atrial Fibrillation (NVAF), who comes to the emergency due to abdominal pain of several hours of evolution. In the previous 24 hours, surgical hysteroscopy had been performed, due to postmenopausal metrorrhagia, in order to rule out the endometrial process.

Complementary tests showed a drop in hemoglobin levels from 14.8 mg/dL to 12.3 g/dL, prothrombin activity 8%,INR 10.58, Prothrombin time (PT) 8%, activated partial thromboplastin time (APTT) 55 seconds. Thus, it is administered 10 mgr Konakion and 1200 IU Human Prothrombin Complex. Two hours later: PT 23%, INR 3.15, PT 2.7 ratio. Renal function was normal.

An abdominal/pelvic CT scan was performed, where pneumoperitoneum was observed in an important amount as well as abundant hemoperitoneum, suggesting uterine perforation.

The patient was moved over specialized hospital.

The last dosis of Dabigatran had been 6 hours ago. Due to the need of urgent surgery, idarazizumab was given in two intravenous boluses of 2.5 g.

Hysterectomy with a double annexectomy was made.12 hours after surgery, anticoagulant treatment with low molecular weight heparin was introduced. She also presented hemorrhagic subhepatic abscess as a surgical complication (not related to dabigatran) that required percutaneous drainage, with good evolution. The patient was discharged continuing treatment with Bemiparin. 20 days later, Dabigatran 150mg/12h was reintroduced without further complications till the present date.

CASE 2

A 55-year-old male receiving anticoagulant Dabigatran 150mg/12h for NVAF, who came to the emergency for pain located in the right renal fossa for the previous 24h, along with dysuria and pollakiuria.

On examination he had signs of severe pain; He was hemodynamically stable with fever (38ºC). Complementary tests: leukocytosis 12000x10e3/mm3, creatinine 1.5 mg/dL, and positive hematuria, Prothrombin activity 96%, APTT 37 seconds. Abdominal ultrasonography and CT scan were performed, showing complicated renal colic.

It was decided to implant double J-catheter, for which we had to reverse the anticoagulant effect of Dabigatran, whose last dose had been taken in the previous 12 hours. For this, idarazizumab was given in two intravenous boluses of 2.5 g, and the intervention was carried out without incident.

24 hours later, after a good clinical evolution of his renal pathology, and before no evidence of bleeding was evident, Dabigatran was restarted at its usual dose of 150mg/12h, with no new complications thus far.

RESULTS

The use of idarucizumab permitted rapid and safe intervention of patients. Both had normal hemostasis during the procedure. 5 g dose of idarucizumab was sufficient and reversal was maintained for 24 hours. One patient presented hemorrhagic complication related to the surgical procedure.

CONCLUSIONS

Idarucizumab is integrated into protocol for the emergency management of patients on dabigatran. Idarucizumab is effective for dabigatran reversal among patients who have uncontrolled bleeding or will be undergoing urgent surgery. Idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran.