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Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow® Assay

Connery, Alexander; Ahuja, Tania; Katz, Alyson; Arnouk, Serena; Zhu, Eric; Papadopoulos, John; Rao, Sunil; Merchan, Cristian
Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.
PMID: 38335531
ISSN: 1533-4023
CID: 5632052

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases

Abdelmessih, Emily; Ahuja, Tania; Wo, Stephanie; Sango, Aaron; Papadopoulos, John; Green, David; Xiang, Elaine
To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.
PMID: 38281232
ISSN: 1573-742x
CID: 5627732

To cool or not to cool: Targeted temperature management to prevent ventricular tachycardia associated with Brugada syndrome [Case Report]

Kiefer, Nicholas J; Ahuja, Tania; Caballero, Alexandra; Pashun, Raymond Anthony
KEY CLINICAL MESSAGE/UNASSIGNED:A robust inflammatory and febrile response from acute viral illness such as with SARS-CoV-2 in patients with Brugada syndrome may lead to triggering of ventricular arrhythmias. The use of targeted temperature management (TTM) using cooling devices may mitigate the febrile triggering of ventricular arrhythmias in patients with Brugada syndrome. ABSTRACT/UNASSIGNED:Brugada syndrome (BrS) is an autosomonal dominant genetic disorder, with a risk of ventricular tachycardia (VT). Triggers of VT in BrS include fevers. Here, we report a case of BrS secondary to SARSs-CoV-2 infection and the use of targeted temperature management (TTM) to decrease fever and prevent VT triggering.
PMID: 38130853
ISSN: 2050-0904
CID: 5612182

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism

Zhu, Eric; Yuriditsky, Eugene; Raco, Veronica; Katz, Alyson; Papadopoulos, John; Horowitz, James; Maldonado, Thomas; Ahuja, Tania
INTRODUCTION/BACKGROUND:The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS:This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS:A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION/CONCLUSIONS:We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.
PMID: 37989523
ISSN: 1751-553x
CID: 5608542

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center

Wong, Adrian; Ahuja, Tania; Cirrone, Frank; Xiang, Elaine
Romiplostim is indicated for immune thrombocytopenia (ITP), though is often used off-label for other indications such as chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia post hematopoietic stem cell transplantation (HSCT). Although romiplostim is FDA approved at a starting dose of 1 mcg/kg, it is often initiated at 2-4 mcg/kg depending on the severity of thrombocytopenia in clinical practice. Given the limited data, but interest in higher doses of romiplostim for indications other than ITP, we aimed to assess our inpatient romiplostim utilization at NYU Langone Health.This was a single-center, retrospective review of 84 adult patients from January 2019 to July 2021. The top three indications were ITP (51, 60.7%), CIT (13, 15.5%), and HSCT (10, 11.9%). The median initial romiplostim dose was 3.8 mcg/kg (range, 0.9-10.8). 51% of patients achieved a platelet count of ≥50 × 109/L by the end of week 1 of therapy. For patients achieving goal platelets by the end of week 1, the median dose of romiplostim was 2.4 mcg/kg (range, 0.9-10.8). There was 1 episode of thrombosis and 1 episode of stroke.We found that higher than FDA-recommended initial doses should be considered to achieve a platelet response. It appears to be safe to initiate romiplostim as higher doses, and to increase doses by greater increments than 1 mcg/kg in order to achieve a platelet response. Future prospective studies are needed to confirm the safety and efficacy of romiplostim in off-label indications and should evaluate clinical outcomes such as bleeding and need for transfusions.
PMID: 37132025
ISSN: 1477-092x
CID: 5503032

Aspirin for Thromboprophylaxis after a Fracture [Comment]

Ahuja, Tania; Green, David
PMID: 37075154
ISSN: 1533-4406
CID: 5464492

To Measure or Not to Measure: Direct Oral Anticoagulant Laboratory Assay Monitoring in Clinical Practice

Ahuja, Tania; Raco, Veronica; Bhardwaj, Sharonlin; Green, David
The need for therapeutic drug monitoring of direct oral anticoagulants (DOACs) remains an area of clinical equipoise. Although routine monitoring may be unnecessary given predictable pharmacokinetics in most patients, there may be altered pharmacokinetics in those with end organ dysfunction, such as those with renal impairment, or with concomitant interacting medications, at extremes of body weight or age, or in those with thromboembolic events in atypical locations. We aimed to assess real-world practices in situations in which DOAC drug-level monitoring was used at a large academic medical center. A retrospective review of the records of patients who had a DOAC drug-specific activity level checked from 2016 to 2019 was included. A total of 119 patients had 144 DOAC measurements (apixaban (n = 62) and rivaroxaban (n = 57)). Drug-specific calibrated DOAC levels were within an expected therapeutic range for 110 levels(76%), with 21 levels (15%) above the expected range and 13 levels (9%) below the expected range. The DOAC levels were checked in the setting of an urgent or emergent procedure in 28 patients (24%), followed by renal failure in 17 patients (14%), a bleeding event in 11 patients (9%), concern for recurrent thromboembolism in 10 patients (8%), thrombophilia in 9 patients (8%), a history of recurrent thromboembolism in 6 patients (5%), extremes of body weight in 7 patients (5%), and unknown reasons in 7 patients (5%). Clinical decision making was infrequently affected by the DOAC monitoring. Therapeutic drug monitoring with DOACs may help predict bleeding events in elderly patients, those with impaired renal function, and in the event of an emergent or urgent procedure. Future studies are needed to target the select patient-specific scenarios where monitoring DOAC levels may impact clinical outcomes.
ISSN: 1687-9104
CID: 5446392

To PLEX or Not to PLEX for Amiodarone-Induced Thyrotoxicosis [Case Report]

Ahuja, Tania; Nuti, Olivia; Kemal, Cameron; Kang, Darren; Yuriditsky, Eugene; Horowitz, James M; Pashun, Raymond A
Amiodarone-induced thyrotoxicosis (AIT) carries significant cardiovascular morbidity. There are two types of AIT with treatment including antithyroid medications and corticosteroids and treatment of ventricular arrhythmias. Therapeutic plasma exchange (TPE) also known as "PLEX" may help remove thyroid hormones and amiodarone. We report a case of PLEX in an attempt to treat cardiogenic shock secondary to AIT. This case highlights the robust rapidly deleterious demise of AIT, specifically in patients with decompensated heart failure. The decision to PLEX or not to PLEX for AIT should be individualized, prior to definitive therapy.
PMID: 38026474
ISSN: 2090-6404
CID: 5617262

Off-Target Effects of Cancer Therapy on Development of Therapy-Induced Arrhythmia: A Review

Leiva, Orly; Bohart, Isaac; Ahuja, Tania; Park, David
BACKGROUND:Advances in cancer therapeutics have improved overall survival and prognosis in this patient population; however, this has come at the expense of cardiotoxicity including arrhythmia. SUMMARY:Cancer and its therapies are associated with cardiotoxicity via several mechanisms including inflammation, cardiomyopathy, and off-target effects. Among cancer therapies, anthracyclines and tyrosine kinase inhibitors (TKIs) are particularly known for their pro-arrhythmia effects. In addition to cardiomyopathy, anthracyclines may be pro-arrhythmogenic via reactive oxygen species (ROS) generation and altered calcium handling. TKIs may mediate their cardiotoxicity via inhibition of off-target tyrosine kinases. Ibrutinib-mediated inhibition of CSK may be responsible for the increased prevalence of atrial fibrillation. Further investigation is warranted to further elucidate the mechanisms behind arrhythmias in cancer therapies. KEY MESSAGES:Arrhythmias are a common cardiotoxicity of cancer therapies. Cancer therapies may induce arrhythmias via off-target effects. Understanding the mechanisms underlying arrhythmogenesis associated with cancer therapies may help design cancer therapies that can avoid these toxicities.
PMID: 36702116
ISSN: 1421-9751
CID: 5597662

Association Between COVID-19 Booster Vaccination and Omicron Infection in a Cohort of Players and Staff in the National Basketball Association [Comment]

Manmadhan, Arun; Ahuja, Tania
PMID: 36472599
ISSN: 1538-3598
CID: 5378662