Argatroban for Anti-Coagulation during Plasma Exchange in a Patient with Cardiac Transplant Rejection and HIT.
Authors: Isaak Edahn J. , Johns Gretchen S. , Yamnitz Brenda A. , Keith Tammie A. , Wagner-Mann Colette , Russo Pierantonio 
Published: October 2019

Abstract
INTRODUCTION:
Plasma exchange has been used with anecdotal success in patients diagnosed with acute humoral rejection after cardiac transplantation. Historically, these exchanges have been performed using citrate as an anti-coagulant. However, citrate can have adverse metabolic effects due to its effect on calcium homeostasis and direct myocardial depression. These adverse effects may result in further reduction of cardiac function in patients already compromised from acute rejection. Heparin is a reasonable alternative, but its use may lead to heparin-induced thrombocytopenia (HIT). Argatroban is a direct thrombin inhibitor which may serve as an alternative to citrate or heparin anti-coagulation when plasma exchange is performed in patients with depressed myocardial function where heparin is not a viable option. We report a case in which a continuous infusion of Argatroban was used as an anti-coagulant during plasma exchange in a cardiac transplant patient with a history of HIT and with a diagnosis of acute humoral rejection and cardiopulmonary collapse.
CASE REPORT:
The patient is a 15 year old male with a history of single ventricle physiology who underwent multiple surgical corrections and who required temporary VAD implantation with two different devices and was bridged to cardiac transplant in June 2003. At the time of heart transplantation, he was diagnosed with HIT. He was readmitted to the ICU in April 2004 in respiratory distress, cardiovascular collapse and renal failure. His ejection fraction (EF) was 15%. The diagnosis of acute humoral rejection was made. Multiple supportive measures were required including ventilatory support, inotropic support, dialysis, and the placement of an intra-aortic balloon pump. Plasma exchange was performed for four consecutive days. On each day one plasma volume was exchanged using 5% albumin for the first half of the exchange and FFP for the second. A continuous Argatroban infusion was introduced into the COBE system via a 3-way stopcock at the access port. Coagulation parameters (PT, aPTT, and INR) were measured before the exchange and at one hour after the initiation of the procedure (Table 1). The patient tolerated the procedures well. There were no hemostatic problems and the EF increased to 50% by day 4. At the end of the plasma exchange treatment, monoclonal anti-rejection treatment was initiated.
CONCLUSION:
Plasma exchange may be used as a therapeutic option to treat acute humoral graft rejection in cardiac transplant patients. When there are issues precluding the use of either citrate or heparin as an anti-coagulant, a reasonable alternative may be Argatroban. This direct thrombin inhibitor has been used in other settings including cardiopulmonary bypass, dialysis and ECMO. In these settings its use was monitored with the activated clotting time. An ideal infusion regimen and monitoring protocol have not been established. In the described case a continuous infusion was used, and progress was monitored with the aPTT. We believe that this case is the first published example of the use of Argatroban in therapeutic plasma exchange and the first example of using continuous infusion with aPTT monitoring.
Coagulation Parameters (Table 1)
Day Rate (mg/hr) Pre-procedure PT (INR)/PT (INR) at 1 hour Pre-procedure aPTT/aPPT at 1 hour 1 7 33 (5.2) / 28.7 (4.1) 31.5/51.3 2 0.5 77 (23) / 38.6 (6.9) 115.6/77.4 3 2 25.3 (3.3) / 30.4 (4.5) 61.5/76.4 4 2 26.9 (3.5) / 28.2 (4.0) 74/70