Edward T. Horn

Safe Use of Hemodialysis for Dabigatran Removal before Cardiac Surgery

OBJECTIVE: To describe a case in which hemodialysis was performed before cardiac transplantation in an attempt to reverse the effects of dabigatran and reduce the risk of bleeding associated with surgery. CASE SUMMARY: A 59-year-old female with heart failure and atrial fibrillation was admitted for orthotropic heart transplant. She had been stable at home with continuous milrinone therapy 0.25 μg/kg/min, amiodarone 200 mg twice daily, and dabigatran 150 mg twice daily for stroke prevention secondary to atrial fibrillation. Upon notification of organ availability, the patient was admitted to the hospital for transplant surgery, with her last dose of dabigatran taken approximately 36 hours before admission. Coagulation studies indicated normal activated partial thromboplastin time, slightly elevated international normalized ratio of 1.2, and elevated thrombin time (TT) of 90.6 seconds (upper limit of normal 19.9 seconds). A hemodialysis catheter was emergently placed and dialysis was initiated. One hour after initiation, TT decreased to 65.5 seconds. After 2.5 hours of dialysis, TT further decreased to 60.2 seconds; at that time, the patient underwent transplantation with no abnormal bleeding during or following surgery. DISCUSSION: Minimal data exist on techniques to reverse the effects of dabigatran in cases of bleeding or emergent surgery. This case examines the efficacy of hemodialysis to decrease dabigatrans effect on clotting assays prior to surgery to reduce the risk of bleeding. In this case, a TT of 60.2 seconds with recent dabigatran administration did not result in abnormal bleeding associated with cardiac surgery. CONCLUSIONS: To our knowledge, this case report represents the first published data on the effects of hemodialysis on dabigatran removal and reversal of anticoagulation associated with dabigatran before surgery. The routine use of preoperative hemodialysis in patients on dabigatran is not recommended; however, the potential efficacy in such circumstances is supported by the successful results in this case.

The pathophysiology of endothelin in complications after solid organ transplantation: a potential novel therapeutic role for endothelin receptor antagonists.

Although short-term allograft survival after solid organ transplantation has improved during the past two decades, improvement in long-term graft survival has been less pronounced. Common complications after transplantation include chronic allograft rejection, nephrotoxicity from calcineurin inhibitors (CNIs), and systemic hypertension, which all impact posttransplantation morbidity and mortality. Endothelin (ET)-1, a potent endogenous vasoconstrictor, inducer of fibrosis, and vascular smooth muscle cell proliferation, may play a key role in both the development of CNI-induced nephrotoxicity and endothelial vasculopathy in chronic allograft rejection. ET-1 levels increase after isograft implantation, and ET-1 plays a key role in CNI-induced renal vasoconstriction, sodium retention, and hypertension. Preclinical studies have demonstrated that endothelin receptor antagonists (ERAs) can reduce or prevent CNI-induced hypertension after renal transplantation. In addition, ERAs can ameliorate CNI-induced renal vasoconstriction and improve proteinuria and preserve renal function in animal models of renal transplantation. ET-1 may also play a significant role in cardiac allograft vasculopathy, and in animal models, ERAs improve pulmonary function and ischemic-reperfusion injury in lung transplantation and hepatic function and structure in liver transplantation. Emerging pharmacokinetic data suggest that the selective ERA ambrisentan may be used safely in conjunction with the most commonly used immunosuppressive agents tacrolimus and mycophenolate, albeit with appropriate dose adjustment. The weight of available evidence pointing toward a potential beneficial role of ERAs in ameliorating common complications after solid organ transplantation must be balanced with potential toxicities of ERAs but suggests that a randomized clinical trial of ERAs in transplant patients is warranted.

Assessing Anticoagulation Practice Patterns in Patients on Durable Mechanical Circulatory Support Devices: An International Survey.

Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the most common target international normalized ratio (INR) was 2–3 for both devices, significant variability exists. Anticoagulation intensity tended to be lower with the HMII, with more centers targeting INR values of less than 2.5. Aspirin monotherapy was the most common antiplatelet regimen; however, the HVAD patients were more likely to be on daily aspirin doses over 100 mg. In addition, parenteral bridging was more frequent with the HVAD device. While 43.8% of respondents indicated an increase in the perceived risk of HMII device thrombosis in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy was infrequent. Our findings verify the wide variety of anticoagulation practice patterns between MCS centers.

Pharmacotherapeutic Management of Gastrointestinal Bleeding in Patients with Continuous-Flow Left Ventricular Assist Devices

Continuous‐flow left ventricular assist devices (CF‐LVADs) have become an integral component of the management in patients with advanced heart failure, serving as destination therapy or as a bridge to heart transplantation. Despite significant advances in the design and longevity of the device, the ongoing risk for bleeding remains a significant concern. The genesis of gastrointestinal bleeding (GIB) in patients with CF‐LVADs is likely multifactorial and may include components of acquired von Willebrand disease, angiodysplasia, and gastrointestinal arteriovenous malformations, as well as additional risk factors such as history of GIB and increased age. Several pharmacotherapy options have been used, but the data surrounding their overall efficacy remain sparse. The necessity for larger prospective studies is essential to further advance the management of this devastating complication. Within this review, we discuss the known pathophysiologic process of CF‐LVAD–related GIB and highlight the therapeutic options discussed within the literature. In addition, we discuss potential therapeutic options based on mechanisms of action as they correlate to known pathophysiologic processes of CF‐LVAD–related GIB. Finally, we provide recommendations for constructing drug therapy regimens in patients with CF‐LVADs who develop GIB.