ALBERT

Description: Introduction: Data on management of upper extremity deep vein thrombosis(UEDVT) in patients with cancer is limited. Patients in this subgroup were excluded from the large clinical trials that showed the efficacy of extended duration low-molecular-weight heparin (LMWH) for cancer-associated thrombosis. Furthermore, risk factors for cancer-associated UEDVT in patients who do not have central lines in situ have not been well defined. The goal of our study was to determine the risk factors for cancer-associated UEDVT and to examine the approach to management of these patients in a real-world setting. Methods: We conducted a retrospective review of 200 consecutive patients who were assessed for cancer-associated UEDVT between January 2010 and June 2014 at a tertiary care center. Outcome measures were recurrent VTE, and major and clinically relevant non-major bleeding. Risk factors for recurrent VTE and bleeding were assessed using multivariable analysis. Results: Median duration of follow-up 11 months. Median age was 61.5 years and 55% were male. Cancer subtypes included colorectal (24%), lung (15%), breast (14%), lymphoma (10%), leukemia (5%), esophageal (4%), pancreatic (4%), head & neck (3%), sarcoma (2%), and others 17%. Metastatic disease at the time of diagnosis was present in 37% of patients and 7% of the study population had a previous history of VTE. Of the study population, 138 (69%) had line-associated UEDVT. Risk factors for UEDVT other than presence of a line after univariate analysis were lung cancer, breast cancer and extrinsic compression of vessels by local tumour on diagnostic imaging. The proportion of patients with UEDVT in the absence of a line according to cancer subtype was as follows: lung cancer (83%), pleural mesothelioma (66%), breast cancer (51%) and head & neck cancer (50%). Of these patients, greater than half had evidence of local mass effect on vessels on diagnostic imaging studies. Of the 138 patients with line-associated UEDVT, 20 (15%) had their line removed within one week of diagnosis for reasons unrelated to thrombosis and 107 (84%) had their line removed after completion of at least 3 months of anticoagulant therapy. Recurrent VTE was documented in 35 patients (17.5%), of which 16 (8%) were UEDVT (PE - 10, lower limb DVT-8, other-2). Recurrent VTE while receiving anticoagulants occurred in 23 (65.7%) of all recurrences and in 10 (62.5%)of UEDVT recurrences. Recurrent VTE occurred in 26 patients with a central line and in 9 patients without a central line. All of the patients with recurrent VTE had solid tumours, and 45% had metastatic disease. Multivariant analysis revealed that male gender(OR 2.42, 95% CI;1.1-5.1,p-value=0.02) and active cancer at the end of follow-up (OR 2.47, 95% CI; 0.1-0.9, p-value=0.04) were the only factors significantly associated with recurrent VTE (Figure 1 and 2). None of the following were significant risk factors for recurrence: type of antineoplastic treatment, accompanying PE, white cell count, initial UEDVT while anticoagulated, cancer stage, previous VTE, number of involved venous segments, removal of line during first week after index event or switching to a different anticoagulant. In the group with UEDVT without a venous catheter, the presence of radiologically proven extrinsic compression of vessels was not statistically associated with recurrent VTE. Patients were treated with LMWH for a median duration of 5 months. Six and 8 patients were switched to rivaroxaban and warfarin, respectively. Clinically relevant non-major bleeding occurred in 24 patients (12%), 61% of the bleeds were gastrointestinal and 83% of the bleeds occurred while receiving anticoagulants. On multivariate analysis, bleeding was significantly associated with ongoing anticoagulation (OR 5.6, 95% CI;1.6-19.3, p-value=0.006) and liver metastasis (OR 7.2, 95% CI;0.9-7.2, p-value=0.05). The use of concomitant clopidogrel or aspirin significantly increased the risk of bleeding (OR 6.6 and 5.5, respectively). Conclusions: While the presence of a venous catheter was the primary risk factor for UEDVT for the majority of our cohort, extrinsic compression of vessels by local tumour appeared to be equally important for certain cancer types. Furthermore, our finding that the majority of recurrent events did not occur in the upper limb suggests that UEDVT may be predictive of overall increased thrombogenic risk rather than just a local effect caused by the line. Disclosures Linkins: Bayer: Honoraria, Research Funding; Pfizer: Honoraria.

Description: Background: Venous thromboembolism (VTE) is one of the most common complications of patients with brain tumors. There is limited data available in the literature on VTE treatment in these patients compared to other cancer types. We evaluated the efficacy and safety of low-molecular weight heparin treatment for newly diagnosed VTE in patients with primary and metastatic brain tumours at a tertiary care centre. Methods: We conducted a matched retrospective cohort study of patients with primary or metastatic brain cancer who were diagnosed with cancer-associated VTE. Cases were selected after completion of a retrospective chart review of consecutive patients who were diagnosed with cancer-associated VTE between January 2010 and January 2014 at the Juravinski Thrombosis Clinic, Hamilton, Ontario, Canada. Controls were age- and gender-matched patients with cancer-associated VTE from the same cohort, but without brain tumours. The primary outcome was first recurrent VTE and secondary outcomes were major bleeding and clinically relevant bleeding. Results: A total of 364 patients with cancer-associated thrombosis were included (182 with primary or metastatic brain tumors and 182 controls). The median follow-up duration was 6.7 (inter quartile range 2.5-15.8) months. The incidence rate of recurrent VTE was 11.0 per 100 patient-year (95% confidence interval [CI]; 6.7-17.9) in patients with brain tumors and 13.5 per 100 patient-year (95% CI; 9.3-19.7) in controls, incidence rate ratio [IRR]; 0.8 (95% CI; 0.4-1.5, p-value=0.43). There was no significant difference in the rate of recurrent VTE in the two groups (log-rank p-value=0.26, Figure 1). The incidence of major bleeding was 8.9 per 100 (95% CI; 5.2-15.4) patient-year in patients with brain tumors versus 6.0 per 100 patient-year (95% CI; 3.4-10.9) in controls, IRR; 0.8 (95% CI; 0.4-1.5, p-value=0.51). There were no significant differences in the risk of major bleeding (Figure 2) and clinical relevant bleeding between the two groups, log-rank p-value 0.9 and 0.8, respectively. When compared to controls, the rate of major gastrointestinal bleeding was lower in patients with brain tumours (0.6% versus 6.0%, p-value=0.003) whereas the rate of intracranial bleeding was higher (4.4% versus 0%, p-value=0.004). Subgroup analysis revealed that the incidence of intracranial bleeding in patients with primary brain tumors was higher than those with metastatic brain tumors, but did not reach statistical significant (6.0% vs 3.5%, p=0.008). Conclusions: Recurrent VTE, major bleeding and clinical relevant bleeding were not significantly different in patients with cancer-associated VTE in the setting of primary or metastatic brain tumours compared with controls. However, intracranial bleedings occurred more frequently in patients with brain tumours. Disclosures Linkins: Pfizer: Honoraria; Bayer: Honoraria, Research Funding.

Description: Background: Bleeding is a major concern in patients who are treated with anticoagulants. To date, there are no studies of predictors of bleeding in cancer-associated thrombosis patients who receive extended duration low-molecular-weight heparin (LMWH). This study aims to determine the incidence and predictors of bleedings in these patients in a real-world setting. Methods: A retrospective cohort (chart review) study was conducted from January 2011 to January 2014 at Juravinski Cancer Center, Hamilton, Canada. Consecutive objectively proven venous thromboembolism (VTE) patients were included if they had active cancer and were planned to receive extended duration LMWH (longer than 4 weeks). The primary outcome measure was the incidence of clinically relevant bleeding, which was defined as bleeding that required investigation, an invasive procedure, hospital admission or withholding LMWH for greater than or equal to 3 days. Secondary outcome measures included incidence of major bleeding (defined by bleeding that was associated with drop of hemoglobin at least 20 g/L or required at least 2 units of red blood cell transfusion, bleeding in critical site or fatal bleeding) and incidence of objectively proven recurrent VTE. Results: Data were available for 1,144 patients with a median follow-up of 8.5 months. The average age (standard deviation, [SD]) of the patients was 63.6 (12.2) years, and 53.6% were female. Concomitant antineoplastic treatment consisted of chemotherapy (45.1%), radiotherapy (5.7%), targeted therapy (1.9%) and combination therapy (17.5%). No antineoplastic treatment was given during the study period to 29.7% of the patients. The cumulative incidence of clinically relevant bleeding was 4.6% at 3 months, 7.3% at 6 months and 10.3% at 12 months, Figure 1. Sites of bleeding were gastrointestinal tract (49.6%), genitourinary tract (16.2%), intracranial (9.0%), muscle and retroperitoneal (8.2%), and others (17.1%). Of the gastrointestinal bleeds, 52.3% occurred in patients who were not documented to have the GI tract as the primary site of malignancy. The cumulative incidence of major bleeding was 5.5% (1.6% of the study cohort had a fatal bleed). At the time of the bleeding event, the mean (SD) hemoglobin was 87.2 (23.1) g/L, mean platelet count (SD) was 251.8 (158.4) x109/L and 61% of patients received a red blood cell transfusion (median 2 unit [range, 1-7]). The independent predictors of bleeding in a multivariable model were hypertension, metastatic disease, prostate cancer, soft tissue sarcoma and recurrent VTE (Table 1.). The presence of brain tumour (primary or secondary) was not statistically significantly associated with an increased risk of clinically relevant bleeding. The cumulative incidence of recurrent VTE was 12.0%. Seventy-six percent of recurrent VTE occurred while patients were receiving anticoagulant therapy. Conclusions: This study suggests that predictors for clinically relevant bleeding in patients who receive extended duration LMWH for treatment of cancer-associated thrombosis include hypertension, metastatic disease, and recurrent VTE, in addition to tumour-site specific characteristics. Investigation into measures to reduce the frequency of gastrointestinal bleeding, the most common form of anticoagulant-related bleeding in both gastrointestinal cancer and non-gastrointestinal cancer, would be beneficial. Table 1. Univariate and multivariate analysis of the predictors of bleeding Variables Univariate analysis Multivariate analysis Odd ratio 95% CI Odd ratio 95% CI P-value Age

Description: Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals  

Description: An amendment to this paper has been published and can be accessed via a link at the top of the paper.