Citations

Abstract Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 Methods: The CCC19 international registry (NCT04354701) aims to investigate complications of COVID-19 in pts with cancer. Our aim was to investigate the frequency of bleeding in hospitalized adult pts with cancer andCOVID-19, enrolled between March 16, 2020 and Feb 8, 2021. The incidence of bleeding complications was captured as defined by CCC19 and included both major and non major bleeding . Associated baseline clinic-pathologic prognostic factors and outcomes such as need for mechanical ventilation, intensive care unit (ICU) admission and mortality rates were assessed Results :3849 pts met analysis inclusion criteria. Bleeding was reported in 276 (7%) pts with median age of 70years; incidence was 6.6 % in females and 7.6 % in males, 6.5% in non-Hispanic white pts, 8.2 % in non-Hispanic Black pts, and 7.8 % in Hispanic pts. 74% had solid cancer and 29% had hematologic malignancies, 33% had received anti-cancer therapy in preceding 30 days, and 8% had surgery within 4weeks. In pts taking antiplatelet or anticoagulant medications at baseline, 7.2% developed bleeding. Need for mechanical ventilation, ICU admission, 30-day mortality, and total mortality were significantly higher in those with bleeding complications compared to those without, p<0.05 Conclusion : We describe the incidence of bleeding in a large cohort of pts with cancer and COVID-19. Bleeding events were observed in those with adverse outcomes including mechanical ventilation, ICU admission, and high mortality; the overall mortality of 43% in patients with bleeding complications is especially notable. This important complication may reflect underlying COVID-19 pathophysiology as well as iatrogenic causes. Figure 1 Figure 1. Disclosures Kumar: Diagnostica Stago: Honoraria. Zon: AMAGMA AND RLZ: Consultancy, Current holder of individual stocks in a privately-held company. Byeff: Pfizer, BMS, Takeda,Teva, Merck, United health: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nagaraj: Novartis: Research Funding. Hwang: astrazaneca,Merck,bayer, Genentech: Consultancy, Research Funding. McKay: Myovant: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calithera: Membership on an entity's Board of Directors or advisory committees; Tempus: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tempus: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Dendreon: Consultancy; Caris: Other: Serves as a molecular tumor board ; Vividion: Consultancy; Sorrento Therapeutics: Consultancy; Bayer: Research Funding. Warner: Westat, Hemonc.org: Consultancy, Current holder of stock options in a privately-held company. Connors: Pfizer: Honoraria; CSL Behring: Research Funding; Alnylam: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Abbott: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: COVID-19 vaccinations in the United States (Janssen, Moderna, and Pfizer) have been deemed generally safe and effective. Rare thrombotic events, now termed vaccine-induced thrombotic thrombocytopenia (VITT), have been reported after the Janssen and Moderna vaccinations. With millions of vaccinations being administered to adults, it is expected that some deep vein thrombosis (DVT) will occur coincidentally with vaccination. Whether COVID-19 vaccinations may contribute to DVT risk more generally (outside of VITT) has not been well studied outside of the initial clinical trials. Aims: Evaluate trends in DVT diagnosis before and after COVID-19 vaccination Methods: Vaccinated patients ≥ 18 years between 11/6/2020 through 6/1/2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. Upper and lower DVT venous Duplex ultrasound (DUS) reports occurring 90 days before and after vaccination date (first dose for Pfizer and Moderna vaccines) were extracted and analyzed with a highly accurate, previously validated, Natural Language Processing (NLP) algorithm for acute DVT. Results: 382,527 patients with at least 1 COVID-19 vaccination were identified. The median age was 61 (IQR 44-72) and 55.3% were male. Pfizer was the most common vaccine administered (n=245,572, 64.2%), followed by Moderna (n=120,683, 31.6%) and Janssen (n=16,272, 4.3%). Most patients (91.5%) receiving vaccinations were from states with Mayo Clinic health services (Minnesota, n=197,834; Wisconsin, n=80,720; Florida, n=42,391; Arizona, n=28,882). The mean age at vaccination was 61.0 (SD 17.7), 56.5 (SD 19.1), and 54.7 (SD 16.3) for Moderna, Pfizer, and Janssen vaccines respectively. Women were most likely to receive the Pfizer (56.3%) compared to Moderna (54.1%) and Janssen (49.5%) vaccines. Non-white patients were most likely to receive Janssen (21%) compared to Moderna (7.7%) and Pfizer (8.2%) vaccines. Among all patients, 7,265 upper and lower venous DUS were performed in 5,960 patients. Figure 1 shows the utilization of DUS before and after COVID-19 vaccination and shows that more patients underwent DUS in the 90 days after vaccination compared to 90 days pre-vaccination. Acute DVT was identified by the NLP algorithm in 808 (714 patients) ultrasounds (11.1%); 656 out of 6136 lower extremity DUS (10.7%) and 152 out of 1129 upper extremity DUS (13.5%). The overall rate of acute DVT (upper and lower) was 1.86 per 1000 patients, consistent with the expected background epidemiologic rate. Figure 2 shows the daily probability of acute DVT by ultrasound report in the 90 days before and after vaccination with a linear regression best fit line showing no overall correlation (R 2 = 0.0). Overall acute DVT post-vaccination occurred on 10.8% of DUS compared to 11.6% pre-vaccination (p=0.28). Among ultrasound reports in Janssen vaccinated patients, 7.0% of post-vaccination compared to 18.0% of pre-vaccination were positive for acute DVT (p=0.003). Among ultrasound reports in Moderna vaccinated patients, 11.0% of post-vaccination compared to 12.7% of pre-vaccination were positive for acute DVT (p=0.15). Among ultrasound reports in Pfizer vaccinated patients, 11.0% of post-vaccination compared to 10.4% of pre-vaccination were positive for acute DVT (p=0.56). Using a Cox proportional hazard model, pre vs post-vaccination time among the same patient cohort was compared for each vaccine. The hazard ratio for DVT post-vaccination was 0.68 (95% CI 0.34-1.38) for Janssen, 1.08 (95% CI 0.86-1.35) for Moderna, and 1.20 (95% CI 0.99-1.46) for Pfizer. After adjusting for age and sex, Pfizer and Janssen's vaccines did not have different risks for DVT compared to Moderna in the 90 days post-vaccination (HR 0.80, 95% CI 0.98-1.25 and HR 0.75, 95% CI 0.42-1.32 respectively). Conclusions: In this large cohort of COVID-19 vaccinated patients, no increased risk for acute DVT post-vaccination was identified for any of the approved vaccinations in the United States. Additionally, no significant difference was seen in the risk for DVT post-vaccination when comparing each vaccine to each other. The probability of acute DVT on ultrasounds in the 90 days post-vaccination was lower than the pre-vaccination period with the Janssen vaccine possibly indicating over-testing in this group. These results provide additional reassurance of the safety of approved COVID-19 vaccines. Figure 1 Figure 1. Disclosures Padmanabhan: Veralox Therapeutics: Membership on an entity's Board of Directors or advisory committees. Pruthi: HEMA Biologics: Honoraria; CSL Behring: Honoraria; Genentech: Honoraria; Instrumentation Laboratory: Honoraria; Bayer Healthcare AG: Honoraria; Merck: Honoraria.