Low ACT After High-Dose Heparin: Is Hemodilution Best Option to Pass by Syclla and Charybdis?

December 15, 2019 • Volume 13 • Number 12 cases-anesthesia-analgesia.org 479 To the Editor We read with great interest the case report of heparin resistance due to underlying conditions other than antithrombin (AT) deficiency.1 The authors clearly highlighted current limitations in heparin monitoring in cardiac surgery. We would like to call caution to some of their suggestions to manage heparin resistance based on our own experiences. First, the authors did not specify which activated clotting time (ACT) device was used. This is clinically important because there can be a significant variability in heparin sensitivity among different manufacturers’ devices depending on underlying conditions. It may be also reasonable to confirm low ACT values using another device from the same manufacturer, or even switching to a different lot of heparin. Second, the authors suggested that elevated factor VIII and fibrinogen levels contributed to heparin resistance on ACT. Although baseline fibrinogen was reported only in the second case, we speculate that fibrinogen was very high in the first case because it remained above 200 mg/dL after having processed 10 cell-saver units. Cell salvage actually removes most plasma fractions including fibrinogen and AT. The fluctuations of ACT during bypass grafting in the first case could be partly explained by ongoing removal of AT via cell saver. In addition, the authors suggested autologous normovolemic hemodilution as an efficacious method to improve heparin sensitivity by diluting procoagulant proteins. However, this approach is concerning because AT is reduced by a large-volume plasma removal, and hemodilution potentially worsens hypercoagulability and heparin resistance.2 Third, heparin dose response (HDR) curve (Hepcon Heparin Management System [HMS]; Medtronic, Minneapolis, MN) was suggested as an alternative to ACT or anti-Xa activity measurement. HDR curve should be distinguished from heparin-protamine titration on Hepcon HMS. HDR curve is an ACT-based test (affected by high FVIII), while heparin-protamine titration is activated by thromboplastin (extrinsic pathway, unaffected by FVIII).3 We typically shift to AT supplementation when ACT remains <400 seconds after Hepcon HMS–derived heparin level is >4.5 mg/kg. Finally, the authors mentioned direct thrombin inhibitors (DTIs) as a rescue anticoagulant in heparin resistance but also raised a concern about postoperative bleeding. In hypercoagulable state (eg, hyperfibrinogenemia) and incomplete anticoagulation, fibrin monomer is generated, which can bind to both heparin and thrombin. The ternary heparin-thrombin-fibrin complex is resistant to AT neutralization, and it can partly explain heparin resistance on ACT. A relatively small dose of DTIs such as argatroban may improve heparin responsiveness on ACT because it is capable of inhibiting heparin-resistant thrombin bound to fibrin.4 If additional heparin doses with AT supplementation fails, low-dose DTI therapy may be considered early to avoid excess heparin doses, potentially leading to a vicious coagulopathy cycle of heparin rebound, and protamine overdose. In summary, we congratulate the authors for managing highly complex clinical problems of heparin anticoagulation. Shifting the balance of coagulation is not an easy task. Practicing cardiac anesthesiologists can learn a lot from both cases, and choose their own course of action between Syclla and Charybdis. E Yoshihisa Morita, MD Division of Cardiac Anesthesia Department of Anesthesia, Pain Management and Perioperative Medicine Henry Ford Hospital Detroit, Michigan Erik Strauss, MD Kenichi A. Tanaka, MD, MSc Department of Anesthesiology University of Maryland School of Medicine Baltimore, Maryland ktanaka@som.umaryland.edu