Major Bleeding After Paracentesis Associated With Apixaban Use: Two Case Reports.

We report 2 patients with compensated cirrhosis and moderate renal impairment who experienced severe bleeding complications from paracentesis during concurrent therapy with apixaban. While paracentesis has traditionally been considered a low bleeding-risk procedure and safe to perform without interruption of therapeutic anticoagulation, the increased concentrations observed in patients with impaired liver function may place these patients at unexpectedly high bleeding risk. Further investigation into the safety of paracentesis in patients with cirrhosis on apixaban may be warranted, as well as additional understanding of the clinical safety of this drug in Child-Pugh B cirrhosis.

The Use of Cangrelor Infusions After Endovascular Aortic Repair With Prophylactic Lumbar Drain Placement.

Perioperative lumbar drains commonly are placed for spinal cord protection in patients undergoing endovascular aortic repair. However, the logistics of postoperative neuraxial drain removal is challenging in the presence of systemic antithrombotic therapy. This retrospective case series describes the novel use of cangrelor infusions in this high-risk setting. All lumbar drains were placed preoperatively, and descriptive data were collected including cangrelor infusion duration, time to lumbar drain removal after the infusion discontinuation, clinical course, and overall patient outcomes. There were no neurologic complications associated with lumbar drain insertion or removal, and median time to lumbar drain removal was 150 minutes after cangrelor infusion discontinuation. While further study is needed to validate its efficacy and safety, this case series highlights the promise of cangrelor infusions for systemic antithrombotic therapy in the cardiovascular/surgical intensive care unit.

Short-term use of an Impella ventricular assist device sterile water-based bicarbonate purge solution for positron emission tomography scanning.

PURPOSE: Impella microaxial ventricular assist devices require a dextrose-based purge solution in combination with heparin or sodium bicarbonate to prevent device dysfunction and stoppage, but the dextrose in these solutions can interfere with positron emission tomography (PET) scans, necessitating an alternative approach. SUMMARY: We describe the short-term use in 2 cases of an alternative purge solution for patients with an Impella 5.5 ventricular assist device undergoing PET scans to rule out infection and malignancy. Sodium chloride solutions cannot be used with Impella ventricular assist devices even for short periods of time due to the potential for motor corrosion. We therefore selected a sterile water-based sodium bicarbonate purge solution, incorporating a short dextrose-free period before and during the PET scan. Imaging was successfully performed with this alternative solution, with monitoring of Impella performance levels and purge parameters throughout the procedure indicating no adverse effects on pump function. CONCLUSION: Our sterile water-based bicarbonate purge solution coupled with a short-term restriction of dextrose is a practical option for PET imaging in patients with an Impella ventricular assist device.

Use of Sodium Bicarbonate Purge Solution in Impella Devices for Heparin-Induced Thrombocytopenia.

Heparin purge solution is recommended to be used in Impella devices to prevent biomaterial buildup and subsequent device dysfunction. The use of sodium bicarbonate purge solution in an Impella device is described in two patients with heparin-induced thrombocytopenia (HIT). The first case details a patient with severe mitral regurgitation and cardiogenic shock who had an Impella CP placed who developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution in addition to systemic direct thrombin inhibitor (DTI) initiation. There was no significant change in Impella purge pressure or flow over the 13 days of Impella use. The second case describes a patient who developed an acute myocardial infarction and subsequent cardiogenic shock for which an Impella CP was placed who also developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution. There was no significant change in purge pressure, flow, or motor current spikes over 11 days of use. In conclusion, we describe the successful use of a novel sodium bicarbonate purge solution utilized in patients with HIT for Impella management alone and in combination with systemic direct thrombin inhibitor therapy. This resulted in no protein deposition in the device gaps or device dysfunction.

Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators.

Programmable control of gene expression via nuclease-null Cas9 fusion proteins has enabled the engineering of cellular behaviors. Here, both transcriptional and epigenetic gene activation via synthetic mRNA and lipid nanoparticle delivery was demonstrated in vivo. These highly efficient delivery strategies resulted in high levels of activation in multiple tissues. Finally, we demonstrate durable gene activation in vivo via transient delivery of a single dose of a gene activator that combines VP64, p65, and HSF1 with a SWI/SNF chromatin remodeling complex component SS18, representing an important step toward gene-activation-based therapeutics. This induced sustained gene activation could be inhibited via mRNA-encoded AcrIIA4, further improving the safety profile of this approach.

Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2 Infection.

Despite the success of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at-risk patient populations, including the immunocompromised. While many neutralizing antibodies have been identified, and several approved, to treat COVID-19, systemic delivery, large doses, and high costs have the potential to limit their widespread use, especially in low- and middle-income countries. To use these antibodies more efficiently, an inhalable formulation is developed that allows for the expression of mRNA-encoded, membrane-anchored neutralizing antibodies in the lung to mitigate SARS-CoV-2 infections. First, the ability of mRNA-encoded, membrane-anchored, anti-SARS-CoV-2 antibodies to prevent infections in vitro is demonstrated. Next, it is demonstrated that nebulizer-based delivery of these mRNA-expressed neutralizing antibodies potently abrogates disease in the hamster model. Overall, these results support the use of nebulizer-based mRNA expression of neutralizing antibodies as a new paradigm for mitigating respiratory virus infections.

Thrombocytopenia in patients treated with heparin, combination antiplatelet therapy, and intra-aortic balloon pump counterpulsation.

OBJECTIVES: Determine the incidence and timing of intra-aortic balloon pump (IABP)-associated thrombocytopenia, if concomitant antiplatelet agents increase the incidence of thrombocytopenia, and the incidence of heparin-induced thrombocytopenia (HIT) in a contemporary IABP population. BACKGROUND: Previous studies predate the current practice of treating acute coronary syndrome patients with heparin and aspirin plus thienopyridines and glycoprotein IIb/IIIa receptor antagonists such that data are unavailable to determine if their co-administration worsens IABP-associated thrombocytopenia. METHODS: A retrospective cohort study of adult IABP patients (n = 107) from 2002 to 2006 was performed to determine the indication for and duration of counterpulsation, platelet counts during and for 7 days postcounterpulsation, medications potentially contributing to thrombocytopenia, and HIT antibody results if obtained. RESULTS: Thrombocytopenia, defined as platelets <150,000/mL or >50% decrease from baseline, occurred in 57.9% of patients. Overall, platelets declined to 60.2 +/- 22.8% of baseline with the mean (+/- standard deviation) nadir on day 2.8 +/- 2.0. Comparing patients who received heparin, aspirin, thienopyridines, and glycoprotein IIb/IIIa antagonists (n = 44) versus heparinized patients +/- aspirin (n = 45), platelet nadirs were 62.7 +/- 20.9% versus 58.3 +/- 23.9% of baseline levels, respectively (P = 0.42). The incidence of HIT was 2.8% in the entire cohort. CONCLUSIONS: IABP-associated thrombocytopenia occurred in 57.9% of this cohort. HIT was diagnosed in 2.8% and should be considered as a diagnosis if platelet counts do not stabilize or continue to fall after 3-4 days of counterpulsation. Increased use of antiplatelet therapy does not impact the degree of thrombocytopenia although the current practice of prompt IABP removal may offset this effect.

Heparin-dependent antibodies and thrombosis without heparin-induced thrombocytopenia.

Although heparin-dependent antibodies (HDAs) typically manifest with thrombocytopenia as in heparin-induced thrombocytopenia (HIT), they may also manifest with preserved platelet counts. We describe a 35-year-old woman who developed severe thrombotic complications due to heparinization and unrecognized HDAs. She had received subcutaneous heparin as prophylaxis for deep vein thrombosis during a 5-day hospitalization for postpartum cardiomyopathy. Five days after discharge (day 1), she developed bilateral lower extremity arterial thrombi and underwent heparinization and successful lower extremity thrombectomies. A pulmonary embolus and hepatic and renal infarcts were then found. On days 2-6, the patient experienced a myocardial infarction, ischemic cerebrovascular accident, recurrent lower extremity arterial thrombus, and splenic infarct. On day 7, blood obtained on day 4 was found to be strongly positive for HDAs. In the interim, the patient had been transitioned to warfarin. Her platelet counts were never less than 75% of baseline and were consistently above 200 x 10(3)/mm(3). Hypercoagulability studies were negative. The patient's score on the Naranjo adverse drug reaction probability scale indicated that the relationship between this adverse reaction and heparin was probable. An extensive MEDLINE search located 22 other reports of patients who developed HDAs, sometimes associated with thrombosis, but whose platelet counts did not decrease. As with our patient, many of these case reports described clinicians who overlooked thrombosis due to HDAs because the patients did not have HIT. Clinicians should be cognizant of this possibility and consider a diagnosis of HDAs in patients with ongoing thrombosis who are receiving heparin therapy. It is strongly recommended that heparin be substituted with another anticoagulant in such cases until the presence of HDAs can be definitively ruled out.

Plasma digoxin concentration fluctuations associated with timing of plasma sampling and amiodarone administration.

A 31-year-old man with dilated cardiomyopathy was hospitalized for new-onset atrial fibrillation. Oral amiodarone 600 mg/day was started to control his arrhythmia, and the patient continued to receive digoxin 0.125 mg/day, which was prescribed 4 days earlier at a heart failure clinic. The patient's digoxin plasma concentration peaked early on hospital day 3 at 2.93 ng/ml; digoxin was withheld. Over the next 3 days, the patient's digoxin plasma concentrations rose and fell daily. These fluctuations correlated with the timing of blood sampling in relation to oral amiodarone administration. The patient's renal function remained stable, and he developed no signs or symptoms of digoxin toxicity. To our knowledge, no case reports have associated significant fluctuations of digoxin plasma concentrations that correspond to the timing of oral amiodarone administration. Tissue-to-plasma redistribution appears to be a possible mechanism for this interaction, with the most significant effect occurring 8-10 hours after amiodarone administration. Clinicians should be aware that digoxin plasma concentrations may not correlate with digoxin tissue concentrations in this setting. When a loading dose of oral amiodarone is required in a patient receiving digoxin, the digoxin dosage should first be reduced, and digoxin therapy should be adjusted based on signs and symptoms of digoxin toxicity.

Clopidogrel desensitization protocol for the treatment of thienopyridine hypersensitivity.

The antiplatelet agent clopidogrel has become a mainstay of treatment of patients with acute coronary syndromes and strokes, and to reduce ischemic complications after percutaneous coronary and peripheral interventions. As the use of this agent has become more widespread, hypersensitivity reactions to clopidogrel have been increasingly recognized. This problem can be difficult to manage, especially in patients who are in need of or have recently undergone intracoronary stenting, as therapeutic alternatives are limited. Our previously published experience shows that desensitization can allow clopidogrel to be used safely in these patients. The protocol is simple, rapid, and can be conducted by a team of cardiology and allergy-immunology specialists. This article outlines the procedural details of the protocol.