Platelet count is associated with cardiovascular disease, cancer and mortality: A population-based cohort study.

INTRODUCTION: Platelet count is used to determine bleeding risk and monitoring thrombopoiesis. While abnormal platelet counts are associated with mortality and morbidity, it is unclear whether it also apply to platelet counts within reference range. We investigated the relationship between platelet count (100-450×109/L) and mortality, development of future cardiovascular disease (myocardial infarction, ischaemic stroke, or peripheral vascular disease), venous thromboembolism, bleeding or cancer in the general population. MATERIAL AND METHODS: We conducted a register-based cohort study of 21,252 adults (≥20years) from the Danish General Suburban Population Study (GESUS). Laboratory results from GESUS were linked to information from national registers regarding morbidity and death. Cox proportional hazard regression was conducted with adjustment for age, sex, smoking status, haemoglobin, leukocyte count, C-reactive protein and Charlson comorbidity index. RESULTS: We found a U-shaped relationship between mortality and platelet count. Mortality was significantly increased for platelet count <175×109/L or >300×109/L. When categorizing platelet count using the interval 201-250×109/L as reference group, platelet count 301-450×109/L was associated with mortality, adjusted hazard ratio (HR)=1.42(95% CI 1.06-1.90) and cardiovascular disease, adjusted HR=1.32 (95% CI 1.03-1.69). Platelet count 100-200×109/L was associated with future cancer, adjusted HR=1.28(95% CI 1.05-1.57), but not with future bleeding or venous thromboembolism. CONCLUSIONS: Platelet count is associated with mortality, future cardiovascular disease, and future cancer.

Tolerance levels of EPID-based quality control for volumetric modulated arc therapy.

PURPOSE: Volumetric modulated arc therapy (VMAT) includes features such as a variable dose rate and gantry speed in addition to the beam modulation achieved with multileaf collimator (MLC) motion patterns employed in intensity modulated radiotherapy. Three tests have previously been proposed for the evaluation of the performance of VMAT delivery. In order to enable a convenient and accurate routine machine quality control (QC) program, the present study proposes tolerance levels for these tests based on a department-wide implementation of an electronic portal imaging device (EPID)-based QC. METHODS: Three different VMAT tests--a picket fence (PF) test, a dose rate versus gantry speed (DRGS) test, and a dose rate versus MLC leaf speed (DRMLC) test--were performed on nine accelerators using two different EPIDs (aS1000 and aS500, Varian Medical Systems). All tests were repeated six times for each accelerator. The images were analyzed using an in-house-developed software. For the PF test, the positions and widths of individual MLC leaf gaps were compared to the mean value. In the DRGS and DRMLC tests, different combinations of dose rate, gantry speed, and MLC leaf speed were used to deliver identical doses to separate parts of the EPID. The tests were evaluated by looking for deviations in the constancy of the measured dose for the preset combinations of dose rate, gantry speed, and MLC leaf speed. RESULTS: For the PF test, a 0.3 mm tolerance level was suggested for the positioning of the MLC leaves. The tolerance level for the gap width was 0.5 mm. For the DRGS and DRMLC tests, a 3% tolerance level was proposed. CONCLUSIONS: With the adapted levels of tolerance for an EPID-based approach, the PF, the DRGS, and the DRMLC tests offer a convenient and accurate machine QC program for linear accelerators used for VMAT.

Determination of autoantibodies to annexin XI in systemic autoimmune diseases.

Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5/137), rheumatoid arthritis (1/21), and systemic lupus erythematosus (1/58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features. A relation between antibodies to annexins and thrombosis has so far only been known for annexin V.