Kreuziger, Lisa Baumann

Background: Standard treatment for catheter-associated upper extremity deep vein thrombosis (UEDVT) is anticoagulation. If catheter removal is otherwise indicated, it is unknown if catheter removal close to the time of initiation of anticoagulation is associated with a higher incidence of pulmonary embolization. Methods: A multicenter retrospective cohort study was performed at 8 participating institutions through the Venous thromboEmbolism Network US (VENUS). ICD-9/10 codes were used to identify patients with hematologic malignancies and upper extremity deep vein thrombosis (UEDVT) from 1/1/2010 through 12/31/2016. Identified patients underwent medical record review to verify diagnostic codes and determine if a catheter was associated with the upper extremity DVT and assess for outcomes. Patients were excluded if the UEDVT was not catheter provoked or if there were associated lower extremity DVT and/or pulmonary emboli. The anticoagulant start and finish date as well as the timing of the catheter removal, total follow up, and death were recorded. Patients started on anticoagulation at the time of their diagnosis were divided into two groups: 1) anticoagulation with delayed (> 48 hrs) or no catheter removal and 2) anticoagulation with early catheter removal (< 48 hrs). Outcomes were also assessed in patients with no anticoagulation initiation but catheter removal as the only treatment. The primary outcome was clinically identified pulmonary emboli within 7 days and the secondary outcome was pulmonary emboli or death from any cause within 7 days. Baseline characteristics were compared between groups using Χ2 for categorical variables, 2-tailed t-tests for continuous variables, and Wilcoxon rank-sum for nonparametric continuous variables. Fisher's exact test was used to evaluate the primary and secondary outcomes. Results: 663 patients with hematologic malignancies and isolated catheter-associated UEDVT underwent chart review. 512 patients were treated with anticoagulation of which 312 underwent early catheter removal while 200 had delayed or no catheter removal (Figure 1). 151 patients received no anticoagulation and 119 underwent catheter removal alone as the treatment for the DVT. Among patients who were treated with anticoagulation, the mean age was 52.6 years and 44% were male; age and sex did not differ between patients with early vs. delayed or no catheter removal (Table 1). Type of hematologic malignancy, type of central catheter, and DVT location were significantly different between groups. Patients with PICC lines were more likely to have early catheter removal (71% vs. 49%). The median platelet count was not significantly different among patients treated with anticoagulation, but was lower in patients treated with catheter removal only. Most patients were initially treated with low molecular weight heparins (LMWH) and anticoagulation treatment did not differ between groups. Pulmonary emboli within 7 days occurred in 2 patients (0.64%) with early catheter removal compared to 1 patient (0.5%) with delayed or no removal (p=1.0). Pulmonary emboli or any cause death within 7 days occurred in 3 patients (1.0%) with early removal compared to 3 patients (1.5%) with delayed or no removal (p=0.68). In patients treated with catheter removal only (no anticoagulation), there were no pulmonary emboli within 7 days and 3 deaths. All 3 patients with pulmonary emboli within 7 days had PICC lines and leukemia/MDS and the sites of most proximal DVT involvement were brachiocephalic veins (2 patients) and subclavian vein (1 patient). Conclusions: In patients with hematological malignancy and catheter-associated UEDVT, removal of catheters within 48 hours was not associated with increased risk of pulmonary emboli compared to delayed or no removal. Disclosures Billett: Albert Einstein College of Medicine: Patents & Royalties: Patent application pending for NETs AI software. Gaddh:Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC: Membership on an entity's Board of Directors or advisory committees. Oo:Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator . Jaglal:NOVARTIS: Consultancy. Streiff:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Portola: Consultancy, Honoraria; Roche: Research Funding. Baumann Kreuziger:Vaccine Injury Compensation Program: Consultancy; CSL Behring: Consultancy.

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal hematologic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ impairment. The incidence of iTTP is higher among African-Americans (AA), however, differences in presentation and outcomes have not been fully investigated. In a multi-center cohort of patients with iTTP from the United States Thrombotic Microangiopathy (USTMA) Consortium, we tested the hypothesis that AA race is an independent predictor of poor outcomes including iTTP related mortality and relapse. Methods: We queried data from the USTMA iTTP registry, which currently includes data from 785 individual patients from 15 institutions across the United States. Data from at least one iTTP episode are available for 734 patients. The cohort is 35.1% (N = 272) White, 58.7% (N = 455) African American, 0.4% (N=3) Asian, 1.8% (N=14) Hispanic, and 4.0 % (N=31) other/unknown race. We restricted our analyses to AA and White participants because of small numbers in the other groups. We compared presenting features and treatments using the chi-squared test and t-test for categorical and continuous variables, respectively. A relapse was defined as a recurrent iTTP episode occurring at least 30 days after last therapeutic plasma exchange. To evaluate relapse-free survival, we included only patients enrolled in the registry at their first TTP episode (144 White and 246 AA) since patients presenting with a relapse as their index episode are already confirmed to have relapsing iTTP. Kaplan Meier analysis was used to compare relapse-free survival in White and AA patients, and a Cox regression model was developed to evaluate the independent effect of race on relapse, adjusting for potential confounders including age, sex, and the use of rituximab. Results: Demographics and presenting features of 390 individuals (144 White and 246 AA) presenting with a first episode of iTTP are shown in Table 1. Presenting symptoms including fever, confusion, seizure, memory deficits, stupor, headache, stroke, chest pain, abdominal pain, fatigue, and dark urine were similar between Whites and AA except for petechiae, which were more frequently documented in Whites (28.8% vs 17.7%, p=0.011). Presenting laboratory studies were also comparable though AA had a higher rate of elevated serum troponin (50.6% vs 32.5%, p=0.003), lower hemoglobin level (8.27 ± 0.13 vs 8.81 ± 0.19, p=0.0176) and platelet count (20.3 ± 1.2 vs 26.2 ± 3.2, p=0.0432). In addition to therapeutic plasma exchange and corticosteroids, rituximab was administered to 23.7% of White patients and 22.7% of AA during their first iTTP episode (P=0.815). Median time to platelet count recovery (days of daily plasma exchange until normal platelet count for two consecutive days) was shorter in AA compared with White patients [5 (IQR 4, 10) vs. 8 (IQR 5, 14), log rank P = 0.004]. AA race remained a significant predictor of the shorter time to platelet count recovery [HR 1.44 (95% CI 1.12, 1.85), P=0.004] after adjusting for rituximab therapy [HR 0.60 (95% CI 0.0.46, 0.80), P<0.001], female sex [HR 0.95 (95% CI 0.73, 1.22), P=0.669], age [HR 0.99 (95% CI 0.99, 1.01), P=0.682], platelet count [HR 1.00 (95% CI 0.99, 1.04), P=0.820] and LDH at presentation [HR 1.00 (95% CI 1.00, 1.00), P=0.525]. Death during the first episode occurred in 8.9% of White patients and 5.5% of AA patients (P=0.206). Relapse-free survival after the first episode of iTTP was lower in AA than White patients (Figure 1). AA race was associated with the reduced relapse free survival [HR 1.79 (95% CI 1.08, 2.98), P=0.024] in a Cox regression model adjusted for age [HR 1.00 (95% CI 0.98, 1.01), P=0.683], sex [HR 0.96 (95% CI 0.60, 1.54), P=0.867], and rituximab therapy [HR 0.93 (95% CI 0.55, 1.59), P=0.806]. Conclusion: African Americans with iTTP have a higher relapse rate and shorter relapse free survival after the first episode of the disease compared with Caucasian patients, which is independent of age, sex and rituximab therapy. Contrary to our hypothesis, acute outcomes of iTTP (time to platelet count recovery and mortality) were not worse in AA patients. The factors contributing to the higher relapse rate in AA with iTTP need to be further investigated. Our findings suggest that AA patients may also benefit from closer follow up. Disclosures Farland: Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Zheng:Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy.