With over 1 million units of blood transfused each year in Canada, their use has a significant clinical and economic impact on our health system. Adequate screening of blood donors is important to ensure the safety and clinical benefit of blood products. Some adverse transfusion reactions have been shown to be related to donor factors (eg, lung injury), whereas other adverse outcomes have been theoretically related to donor factors (mortality and infection). Our clinical trial will test whether male donor blood leads to a greater benefit for transfusion recipients compared with female donor blood.We have designed a pragmatic, double-blind, randomised trial that will allocate transfusion recipients to receive either male-only or female-only donor transfusions. We will enrol 8850 adult patients requiring at least one transfusion at four sites over an approximate 2-year period. Randomisation and allocation will occur in the blood bank prior to release of the units of blood for transfusion. Our primary outcome is mortality. An intent-to-treat analysis will be applied using all randomised and transfused patients. The principal analysis will be a survival analysis comparing the time from randomisation to death between patients allocated to male donor red blood cells (RBCs) and female donor RBCs.Approval has been obtained from research ethics boards of all involved institutions, as well as from privacy offices of Canadian Blood Services, Institute for Clinical Evaluative Science and The Ottawa Hospital Data Warehouse. Our findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.NCT03344887; Pre-results.
von Willebrand factor (vWF) antigen levels are elevated in patients with end-stage kidney disease (ESKD). We determined the quantitative and qualitative abnormalities of vWF and factors influencing vWF proteolysis in participants with ESKD compared with age-matched controls and determined the association between abnormalities in vWF and mortality over 4 years of follow-up. vWF : Ag and von Willebrand factor propeptide (vWFpp) levels, vWF functional activity (vWF :RCo), vWF multimer profiles, ADAMTS-13, thrombospondin 1 (TSP-1), and interleukin 6 (IL-6) were evaluated before and after a single hemodialysis treatment in 55 individuals with vascular disease and an age-matched group of controls (n = 21). vWF : Ag and vWF activity were significantly higher in the ESKD patients and levels increased further following the dialysis procedure. The percentage of high molecular weight multimers (%HMWMs) was significantly elevated in the ESKD patients compared with controls. TSP-1 was lower and IL-6 was higher providing possible explanation for the increase in %HMWM in ESKD. The %HMWM dropped significantly in the postdialysis sample. Mortality at 4 years was significantly associated with vWF : Ag. There are higher plasma vWF : Ag levels and a small increase in HMWMs in the ESKD milieu. The acute drop in the %HMWM of vWF postdialysis appears to be due to shear forces encountered during the dialysis procedure. The contribution of these abnormalities to either a pro-thrombotic and/or pro-bleeding phenotype in this population requires further study.
Introduction/Aim Our aim was to generate, optimize and validate a self‐administered bleeding assessment tool (self‐ BAT ) for von Willebrand disease ( VWD ). Methods In Phase 1, medical terminology in the expert‐administered International Society on Thrombosis and Haemostasis ( ISTH )‐ BAT was converted into a Grade 4 reading level to produce the first version of the Self‐ BAT which was then optimized to ensure agreement with the ISTH ‐ BAT . In Phase 2, the normal range of bleeding scores (BSs) was determined and test–retest reliability analysed. In Phase 3, the optimized Self‐ BAT was tested as a screening tool for first time referrals to the Haematology clinic. Results Bleeding score from the final optimized version of the Self‐ BAT showed an excellent intra‐class correlation coefficient ( ICC ) of 0.87 with ISTH ‐ BAT BS in Phase 1. In Phase 2, the normal range of BSs for the optimized Self‐ BAT was determined to be 0 to +5 for females and 0 to +3 for males and excellent test–retest reliability was shown ( ICC = 0.95). In Phase 3, we showed that a positive Self‐ BAT BS (≥6 for females, ≥4 for males) has a sensitivity of 78%, specificity of 23%, positive predictive value ( PPV ) of 0.15 and negative predictive value ( NPV ) of 0.86 for VWD ; these figures improved when just the females were analysed; sensitivity of 100%, specificity of 21%, PPV = 0.17 and NPV = 1.0. Conclusion We show an optimized Self‐ BAT can generate comparable BS to the expert‐administered ISTH ‐ BAT and is a reliable, effective screening tool to incorporate into the assessment of individuals, particularly women, referred for a possible bleeding disorder.
Guidelines state that Ringer's lactate (RL) should not be co-administered with packed red blood cells (PRBC) due to a potential risk of clotting. The purpose of this study was to determine whether RL causes clotting in PRBC with the currently used preservative, saline-adenine-glucose-mannitol (SAGM).Phase 1: Samples from 12 units of SAGM-PRBC were diluted from 0-97.5% with RL and normal saline (NS), incubated for 30 min, and passed through 40 μm filters. Additional samples were frozen and batch analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure prothrombin activation fragment 1 + 2 (F1 + 2), indicative of thrombin generation. Packed red blood cells were also diluted, flushed with crystalloid using a rapid transfusion model, and filtered. Phase 2: Eight further units were serially diluted with RL and incubated for 30, 60, 120, 180, and 240 min. Fresh samples were analyzed by filtration and ELISA.Phase 1: No clotting was seen during filtration or using the transfusion model with NS or RL. The F1 + 2 ranged from 2.28 to 154.37 pmol·L⁻¹ in NS dilutions and from 2.80 to 1675.93 pmol·L⁻¹ in RL dilutions, indicating coagulation in some samples. Phase 2: No clotting was observed within 60 min by filtration or ELISA. However, 4 of the 8 units showed clots in the filters of some dilutions between 120 and 240 min.No clotting was detected at any dilution of RL with SAGM- preserved PRBC within 60 min, but clotting was detected with extended incubation. The results indicate RL can be safely co-administered with PRBC during rapid transfusion (< 60 min).
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