Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study.

The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20-directed regimen.

The complexities of transfusion reactions: Coexistence of a delayed haemolytic transfusion reaction and post-transfusion purpura.

Background And Objectives: Immune-mediated acute or delayed transfusion reactions occur when there is immunological incompatibility between transfused blood products and recipient's antibodies. Acute haemolytic transfusion reactions occur within 24 h and are delayed after 24 h up to 10 days following transfusion, whereas post-transfusion purpura (PTP) typically occurs 7-10 days post-transfusion. We present a case of a previously transfused and recently post-partum female who developed both delayed haemolytic transfusion reaction (DHTR) and PTP.

Anaemia in elderly patients at discharge from intensive care and hospital.

Background And Objectives: Anaemia is common in the elderly and is recognized as a risk factor for several adverse outcomes in older adults, including hospitalization, morbidity and mortality. The study aims were to examine the prevalence of anaemia in elderly patients at discharge from the intensive care unit (ICU) and hospital.

Materials And Methods: Patient randomized under the INFORM trial and with an ICU admission were included.

Extending the post-thaw viability of cryoprecipitate.

Background: Cryoprecipitate has a short post-thaw expiry time of 6 h. The aim of this study was to assess the stability and function of cryoprecipitate components (FVIII, fibrinogen, vWF, and FXIII) and cryoprecipitate sterility up to 120 h post-thawing when stored at two temperatures (2-6°C and room temperature [20-24°C]).

Methods And Materials: Twenty batches (110 individual units) of time-expired, thawed cryoprecipitate were collected.

Direct oral anticoagulants: evidence and unresolved issues.

Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety.

Warming blood prior to transfusion using latent heat.

Objective: Major trauma is associated with blood loss and hypothermia. It is common to replace lost fluid with red cells stored at 2-6°C, and/or colloid/crystalloid fluid stored at ambient temperature, thus increasing hypothermia risk. At trauma and medical retrieval sites, mains electricity powered fluid warmers cannot be generally used.

Resistance to proteasome inhibitors and other targeted therapies in myeloma.

The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents.

Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial.

Background: No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days.

Methods: We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions.

Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion.

Background: Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients.

Methods: In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio.

Rationale and Design of the Informing Fresh versus Old Red Cell Management (INFORM) Trial: An International Pragmatic Randomized Trial.

Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients.

Effect of aspirin on mortality in the primary prevention of cardiovascular disease.

Objective: The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods: Eligible articles were identified by searches of electronic databases and reference lists.

Point-of-care testing for assessment of adequacy of oral antiplatelet therapy in patients with cardiovascular disease.

Studies with recently introduced point-of-care (POC) platelet function tests have shown that individuals are variably responsive to aspirin and clopidogrel therapy, and that hyporesponsiveness to antiplatelet therapy is associated with an increased risk of cardiovascular events. However, the currently available POC tests have undergone only limited clinical evaluation and clinicians are uncertain about the best POC test, the optimal cut-off point to define hyporesponsiveness in different patient populations and clinical settings, the appropriate management of patients demonstrating hyporesponsiveness and the cost effectiveness of adjusting treatment on the basis of the results of POC platelet function testing. Several large randomized controlled trials currently underway are examining whether adjusting antiplatelet therapy on the basis of a POC test result can improve patient-important outcomes.

New anticoagulants for atrial fibrillation.

Atrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists.

Accuracy and clinical usefulness of the CoaguChek S and XS Point of Care devices when starting warfarin in a hospital outreach setting.

Objective: To assess clinical usefulness of CoaguChek S and XS monitors to measure International Normalised Ratio (INR) when starting warfarin in community patients.

Methods: INR in consecutive patients starting warfarin plus enoxaparin was measured in the laboratory and on capillary blood at home using CoaguChek S or XS point of care (POC) devices. INR was measured daily until >2.

The risk of iatrogenic bleeding in acute coronary syndromes and long-term mortality.

Purpose Of Review: This review examines the association between bleeding and adverse outcomes in patients with acute coronary syndrome and explores mechanisms behind this association and strategies for reducing bleeding complications in acute coronary syndrome.

Recent Findings: Bleeding is a common complication of antithrombotic treatment in acute coronary syndrome, and major bleeding occurs in around 5% of patients. Important risk factors for major bleeding include increasing age, female sex, renal impairment, and invasive procedures.