Faculty Bibliography

INTRODUCTION/UNASSIGNED:Platelet hyperreactivity is linked to inflammation and cardiovascular risk in nonpregnant populations, but its relationship to placentally mediated pregnancy outcomes is undefined. We prospectively evaluated platelet hyperreactivity in pregnancy and subsequent ischemic placental disease (IPD), and examined aspirin's (ASA) effect on platelet activity by baseline platelet phenotype. METHODS/UNASSIGNED: RESULTS/UNASSIGNED:Of 66 pregnant participants recruited, 61 had first-trimester LTA; 20 (32.8%) had platelet hyperreactivity. Participants with hyperreactivity were more likely to develop IPD than those without (55% versus 24%, adjusted odds ratio [aOR] 3.77 (95% CI [1.05-13.53]), with consistent directionality across individual components despite low event frequencies. Participants with platelet hyperreactivity showed greater platelet aggregation to ADP, collagen, and low-dose AA. Platelet transcriptomic profiling distinguished participants with versus without platelet hyperreactivity and revealed differential expression of pathways related to platelet activity, energy metabolism, and immune regulation. Among 45 high-risk participants recommended ASA, those with hyperreactivity exhibited higher AA-induced aggregation (24% vs 12.5% platelet aggregation, p=0.01) despite similar serum TxB2 levels. CONCLUSION/UNASSIGNED:First-trimester platelet hyperreactivity was present in approximately one-third of participants and was independently associated with increased risk of IPD. Participants with platelet hyperreactivity demonstrated distinct transcriptomic signatures and greater platelet aggregation despite ASA use. Together, these findings support a contributory role for platelets in placental ischemic pathology and highlight the need to elucidate mechanisms and develop platelet-targeted preventive strategies.

BACKGROUND:Extended-course enoxaparin is increasingly used after bariatric surgery to prevent venous thromboembolism (VTE), the leading cause of death after bariatric surgery. Direct oral anticoagulants are widely used for extended thromboprophylaxis outside of bariatric surgery and offered to patients in our program who cannot tolerate or obtain enoxaparin. We evaluated the safety and efficacy of apixaban 2.5 mg twice daily relative to a weight-based dose of enoxaparin 40 mg or 60 mg twice daily for 30 days after discharge following sleeve gastrectomy. METHODS:Patients aged ≥18 years who underwent laparoscopic sleeve gastrectomy from 2019 to 2024 at a single high-volume urban academic center were included. Bleeding and thrombosis outcomes within 30 days were compared between patients receiving enoxaparin 40 mg twice daily or apixaban 2.5 mg twice daily. Weighted modified Poisson analyses were used to obtain covariate balance and assess differences in bleeding and thrombosis events. RESULTS:A total of 5921 patients were included for analysis (5274 enoxaparin 40 mg twice daily, 486 enoxaparin 60 mg twice daily, and 161 apixaban 2.5 mg twice daily). The 30-day thrombosis rate was significantly lower with enoxaparin versus apixaban (.1% versus 1.9%, P < .001). The composite outcome (VTE, portomesenteric venous thrombosis, and major/minor bleeding) was also significantly lower with enoxaparin versus apixaban (1.7% versus 5.6%, P < .01). In adjusted analyses, apixaban was associated with a relative risk of 12.09 for thrombosis (95% confidence interval [CI], 5.71-31.18), 1.93 for bleeding (95% CI, 1.27-3.00), and 2.59 (95% CI, 2.06-3.27) for any adverse outcome relative to enoxaparin. CONCLUSION/CONCLUSIONS:Enoxaparin is associated with both lower thrombosis and bleeding rates compared with apixaban for extended thromboprophylaxis after sleeve gastrectomy.

OBJECTIVE:To investigate the relationship between platelet indices (count, size and production/immaturity) and hypertensive disorders of pregnancy. STUDY DESIGN/METHODS:This was a secondary analysis of a prospective cohort of pregnant individuals followed from first trimester through delivery at an academic tertiary care institution. Routine platelet indices obtained prospectively during prenatal care and delivery were compared between those who developed a hypertensive disorder of pregnancy and those who did not. We assessed platelet count (by trimester), mean platelet volume, and immature platelet fraction measured as percent (%) and absolute count. Data were analyzed using Fisher's Exact test, chi-square test, and multivariable logistic regression. P < 0.05 was considered statistically significant. RESULTS: = 0.01) compared to those without a hypertensive disorder of pregnancy, after adjusting for age, race/ethnicity, obesity, nulliparity, and chronic hypertension. The prevalence and likelihood of a hypertensive disorder of pregnancy increased with increasing mean platelet volume, as well as with both the percent and absolute immature platelet fraction. There was no difference between groups in platelet count in the first trimester, second trimester, or at delivery. CONCLUSIONS:An increase in platelet size and immaturity was observed in those with a hypertensive disorder of pregnancy. These data support further investigation of platelets in the mechanisms of the development of hypertensive disorders of pregnancy and the use of platelet indices to better identify high risk groups in pregnancy.

In this case report, we present a patient with the rare plasmacytoid variant of urothelial cancer. Notable elements of his course include: complete response to neoadjuvant paclitaxel, gemcitabine, cisplatin, development of metastatic disease to the rectum, sustained disease control with dual HER2 targeting therapy, and subsequent complete response to enfortumab vedotin. Plasmacytoid urothelial cancer accounts for just 1-3% of all urothelial cancer cases and is associated with more aggressive disease, with a propensity for intra-abdominal spread and poor response to neoadjuvant therapy. Preliminary data indicate that the variant may generally have high levels of HER2 expression. We review the history of HER2 targeting in metastatic urothelial cancer, which has included single-agent as well as combination with chemotherapy; there are ongoing biomarker-based clinical trials. Furthermore, we highlight the complete response to enfortumab vedotin. To date, this is the first report of efficacy for enfortumab vedotin in the plasmacytoid variant.