Faculty Bibliography

BACKGROUND:Little data exists regarding reversal and resumption of antithrombotics following left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH). METHODS:Prospectively collected data of LVAD patients with ICH was reviewed. Coagulopathy reversal agents, antithrombotic regimens and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent ICH, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. RESULTS:Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal and 3 of these had hemorrhage expansion or died before repeat imaging. One (4%) had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17(100%) survivors in a median time 8 days for antiplatelet agents, and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (N=4) had a trend toward more thrombotic events (1.37 vs. 0.14 events-per-patient-year [EPPY],P=0.08), including more fatal thrombotic events (0.34 EPPY vs. 0.08, P=0.89) compared to those resuming warfarin±antiplatelet (N=14). Non-fatal hemorrhage event rates were 0.34 EPPY in the warfarin±antiplatelet vs. 0 EPPY in the antiplatelet alone group (P=0.16). No fatal hemorrhagic events occurred. CONCLUSIONS:Reversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred.

BACKGROUND:Anticoagulation with warfarin is common prior to heart transplantation and complicates perioperative management. METHODS:This single-center, non-interventional, retrospective cohort study evaluated heart transplants before and after institution of a PCC-based preoperative warfarin reversal protocol for heart transplantation. Patients with international normalized ratio (INR) > 1.5 received who PCC prior to heart transplant surgery were compared to a control group prior to implementation of a PCC protocol. Co-primary endpoints were utilization of individual blood products. Secondary endpoints included in-hospital mortality, reoperation for bleeding, delayed sternal closure, thromboembolic events, duration of chest tube use, time to extubation, ICU length of stay, and hospital length of stay. RESULTS:The study included 106 consecutive heart transplant patients (PCC cohort = 57, historical control cohort = 49). There was a significant reduction in FFP utilization in the PCC cohort (6 units vs 8 units, p=0.002). Rates of PRBC and platelet transfusion were similar between groups. There was a significant increase in the incidence of cryoprecipitate utilization in the PCC cohort, which can likely be attributed to decreased antifibrinolytic utilization. There were no differences in secondary endpoints between groups, including thromboembolic events. CONCLUSIONS:This study found that a PCC-based warfarin reversal protocol significantly reduced FFP utilization compared to historical controls without impacting other clinically important surgical outcomes. These data suggest that PCC is a valuable tool for INR normalization that could safely reduce FFP administration and offer a practical alternative to traditional approaches for INR reversal prior to heart transplantation.

Purpose: The opioid epidemic has expanded the cardiac donor pool, but the concern for primary graft dysfunction (PGD) remains a barrier to wider utilization of these hearts. We analyzed donor characteristics in transplanted and discarded cardiac allografts from overdosed donors (ODD) to determine if viable ODD hearts are being unnecessarily discarded due to inappropriate bias. Method(s): Data on adult cardiac transplantation from 2010-2017 were provided by the SRTR. Eight donor characteristics associated with PGD were analyzed: age, gender, hypertension, high creatinine, cocaine abuse, inotropic support, LVEF, and cardiac arrest. Donor characteristics of transplanted and discarded hearts were compared between ODD and non-ODD. Result(s): ODD comprised 11% (1710/15904) of transplanted hearts and 7% (2600/32678) of discarded hearts. Among transplanted hearts, ODD more frequently were younger than 50 (98% vs 90%), did not have hypertension (86% vs 83%), and did not require inotropic support (62% vs 55%) compared to non-ODD; ODD less frequently were male (63% vs 70%), had no history of cocaine abuse (57% vs 84%), or had creatinine <=1.5 (62% vs 81%). Among discarded hearts, ODD more frequently were younger than 50 (87% vs 46%), had no history of hypertension (78% vs 49%), and did not require inotropic support (51% vs 41%); ODD less often had no history of cocaine abuse (50% vs 86%) or creatinine <=1.5 (61% vs 69%) (Table). Donors known to have at least 6 of 8 favorable qualities comprised 36% (942/2600) of discarded ODD hearts, compared to 28% (9152/32678) of discarded non-ODD hearts (p<0.001). The most common reasons given for discard of ODD hearts with favorable qualities were poor organ function (18%), refusal by all programs (16%), and lack of recipient (11%). Conclusion(s): ODD hearts with favorable qualities are being discarded at disproportionally higher rates than non-ODD hearts. Further studies and better documentation are needed to understand current discard practices and if further expansion into this donor pool is appropriate.

Purpose: Heart transplantation (HTx) from hepatitis C virus (HCV) positive donors to HCV negative recipients may reduce waitlist time and increase access to viable organs. Direct acting antivirals (DAAs) are highly successful at curing HCV infection, but the effect of DAAs on the pharmacokinetics of calcineurin inhibitors is largely unknown. We describe the effect on tacrolimus dosage requirements in recipients of HCV viremic donors. Method(s): We retrospectively reviewed HCV negative HTx patients who received a HCV positive organ. All patients received an 8 week course of glecaprevir-pibrentasvir (GP) for HCV treatment and were on standard triple immunosuppression therapy. Patients receiving concomitant medications that affect tacrolimus metabolism were excluded. All tacrolimus dosages and trough levels were collected from the time of initiation post-HTx until 1 month after completion of GP treatment. Tacrolimus dose normalized concentrations using the concentration:dose ration (ng/mL:mg/kg) were compared before, during, and after GP treatment. Result(s): Seven HTx recipients were included in the analysis. Tacrolimus dose normalized concentrations were 124.8, 163.4, and 196.7 (ng/mL)/(mg/kg/d) before, during and after GP treatment, respectively (Figure 1). Tacrolimus dosage requirements did not differ during GP treatment as compared to before or after GP treatment. The percentage of tacrolimus trough levels within goal range and the incidence of supratherapeutic tacrolimus levels, was 51% vs. 41% and 4% vs. 0% during GP treatment as compared to after GP treatment. Conclusion(s): We did not find a difference in tacrolimus dosage requirements while receiving GP treatment as compared to before or after GP treatment; however, this study was limited by a small sample size. No empiric dosage adjustments can be recommended when initiating or discontinuing GP treatment at this time. Further data will be needed to strengthen these findings.