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Use of the CytoSorb® filter for elimination of residual therapeutic argatroban concentrations during heparinized cardiopulmonary bypass for heart transplantation
Andreas Koster1, Helmuth Warkentin1, Vera von Dossow1, and Michiel Morshuis2 | 1 Institute of Anesthesiology and Pain Therapy, Bad Oeynhausen, Germany | 2 Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Bad Oeynhausen, Ruhr-University Bochum, Germany Perfusion 2022; epub
06/08/2022
New!Peer Reviewed Published DataTransplantCardiac surgeryCase of the weekCase reportCPBDrug removalIntra-Op
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Summary
CoW 25/2022 – This case reports on a 34-year-old male patient with a medical history of a correction of Fallot tetralogy, who was scheduled for heart transplantation.
Summary
This is a case report about a 34-year-old patient who, after a five week wait in hospital, was offered a donor heart that had to be transplanted within 2 hours. Because of a history of heparin-induced thrombocytopenia (HIT), the patient had been placed preoperatively on the anticoagulation drug argatroban for which there is currently no reversal agent. Despite ceasing the continuous infusion of argatroban immediately, concentration only declined from 0.60 mug/ml to 0.58 mug/ml before surgery, with the activated clotting time (ACT) value remaining very high (223 s). Microvascular bleeding was observed on chest incision, therefore a CytoSorb column was integrated into the system of the heparin-anticoagulated cardiopulmonary bypass (CPB) circuit, with a flow of 400 mL/min provided during the 150 mins of extracorporeal circulation. The argatroban concentration after weaning from CPB was 0.04 mug/ml and satisfying hemostasis was achieved after protamine administration. Despite severe bleeding within the context of perioperative use of argatroban having been described, the 12-h postoperative blood loss was only 580 mL. The authors note that the availability of a technology for quick elimination of high therapeutic concentrations of argatroban may have a significant impact on the safety profile of this drug, and that the use of CytoSorb might be an effective tool that has the potential to fulfil these criteria.
Comment from CytoSorbents
Argatroban is a direct thrombin inhibitor used instead of heparin for anticoagulation in cases of heparin-induced thrombocytopenia. This is the first published clinical case report that suggests a potential relevant removal of argatroban, but there are a number of other published papers (case reports / case series) that confirm the feasibility of argatroban anticoagulation without the need for additional precautions. Relevant in-vitro removal of argatroban has been shown, however, with the exception of this case report, there has been no signal towards clinically important removal from the published literature. Based on the currently available, inconclusive data, we recommend regular monitoring of aPTT when argatroban is used as anticoagulant during CytoSorb application.
Case presentation
The patient further revealed severe biventricular dysfunction requiring moderate inotropic support as well as multiorgan dysfunction (Model of End Stage Liver Disease excluding International Normalized Ratio [INR] (MELD XI) score of 12.3)
Due to a previous history of heparin-induced thrombocytopenia (HIT), systemic anticoagulation with argatroban was initiated and monitoring of the drug was performed with a target plasma concentration of 0.4–1.0 µg/ml
After a five week wait in hospital, a donor organ was finally offered, which, however, had to be transplanted within 2 hours due to logistical reasons
The infusion of argatroban was immediately stopped and blood samples taken to measure the actual argatroban plasma concentration
Despite ceasing the continuous infusion of argatroban immediately, concentration only declined from 0.60 µg/ml to 0.58 µg/ml within 2 hours before surgery, with the activated clotting time (ACT) value remaining very high (223 s)
With chest incision, 1 g of tranexamic acid was given to the patient and 0.5 g added to the cardiopulmonary bypass (CPB) system
During sternotomy, massive coagulopathy was evident and, as dialysis or continuous hemofiltration do not result in significant clearance of argatroban plasma levels, it was decided to incorporate a CytoSorb hemoadsorption column into the CPB circuit for possible enhanced extracorporeal elimination of argatroban
Treatment
One CytoSorb hemoadsorber was provided during the 150 mins of extracorporeal circulation
The CytoSorb column was integrated into the system of the heparin-anticoagulated CPB circuit. No hemofiltration was performed. During CPB, two units of red blood cell (RBC) concentrates were transfused
Blood flow rate: 400 mL/min
Measurements
Hemodynamics and need for inotropes
Argatroban plasma concentrations
Hemostasis as well as perioperative blood loss
Results
Weaning from CPB was possible with moderate inotropic support
Argatroban concentration declined from 58 µg/ml to 0.04 µg/ml during hemoadsorption
This was associated with a satisfying hemostasis after protamine administration with only modest microvascular bleeding observed in the operation field. The 12-h postoperative blood loss was only 580 mL
Patient Follow-up
The chest could be closed 1 hour after the end of CPB and the patient was transferred to the intensive care unit
Conclusion
This is the first report about the use of the CytoSorb column to eliminate high therapeutic concentrations of argatroban
The authors note that the availability of a technology for quick elimination of high therapeutic concentrations of argatroban may have a significant impact on the safety profile of this drug, and that the use of CytoSorb might be an effective tool that has the potential to fulfil these criteria.
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