A no-prophylaxis platelet-transfusion strategy for hematologic cancers.

BACKGROUND: The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis. METHODS: We conducted this randomized, open-label, noninferiority trial at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when morning platelet counts were less than 10×10(9) per liter. Eligible patients were persons 16 years of age or older who were receiving chemotherapy or undergoing stem-cell transplantation and who had or were expected to have thrombocytopenia. The primary end point was bleeding of World Health Organization (WHO) grade 2, 3, or 4 up to 30 days after randomization. RESULTS: A total of 600 patients (301 in the no-prophylaxis group and 299 in the prophylaxis group) underwent randomization between 2006 and 2011. Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2; P=0.06 for noninferiority). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation. CONCLUSIONS: The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis. A significant number of patients had bleeding despite prophylaxis. (Funded by the National Health Service Blood and Transplant Research and Development Committee and the Australian Red Cross Blood Service; TOPPS Controlled-Trials.com number, ISRCTN08758735.).

Guideline on the investigation and management of acute transfusion reactions. Prepared by the BCSH Blood Transfusion Task Force.

Although acute non-haemolytic febrile or allergic reactions (ATRs) are a common complication of transfusion and often result in little or no morbidity, prompt recognition and management are essential. The serious hazards of transfusion haemovigilance organisation (SHOT) receives 30-40 reports of anaphylactic reactions each year. Other serious complications of transfusion, such as acute haemolysis, bacterial contamination, transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO) may present with similar clinical features to ATR. This guideline describes the approach to a patient developing adverse symptoms and signs related to transfusion, including initial recognition, establishing a likely cause, treatment, investigations, planning future transfusion and reporting within the hospital and to haemovigilance organisations. Key recommendations are that adrenaline should be used as first line treatment of anaphylaxis, and that transfusions should only be carried out where patients can be directly observed and where staff are trained in manging complications of transfusion, particularly anaphylaxis. Management of ATRs is not dependent on classification but should be guided by symptoms and signs. Patients who have experienced an anaphylactic reaction should be discussed with an allergist or immunologist, in keeping with UK resuscitation council guidelines.

The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab.

In Paroxysmal nocturnal haemoglobinuria (PNH), pregnancy is associated with increased maternal and foetal complications to such an extent that the condition has been considered relatively contra-indicated in PNH. Eculizumab has revolutionized the treatment of PNH. We evaluate its use in pregnancy to date. We report on seven patients exposed to eculizumab at different stages of pregnancy including the first two patients to receive the drug from conception to delivery. There was no evidence of complement blockade from cord blood samples taken at delivery. Eculizumab appears safe to use in this setting and is likely to prevent many of the complications usually observed.

Quality of life and use of red cell transfusion in patients with myelodysplastic syndromes. A systematic review.

The main treatment for many patients with Myelodysplastic Syndromes (MDS) remains red cell transfusion to attenuate the symptoms of chronic anemia. Fatigue can reduce a patient's health related quality of life (HRQoL), but there is little understanding of the optimal use of transfusions to improve this. A systematic review was performed to identify and appraise publications reporting the use of HRQoL instruments in patients with MDS. A total of 17 separate studies were identified that used 14 HRQoL instruments, but only one MDS disease specific HRQoL instrument (QOL-E) was reported. Two well established HRQoL instruments were most often used in MDS research (variants of the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30)). Several common problems were identified in the published literature including a lack of power calculations to detect clinically relevant changes, small sample sizes and significant attrition rates for completion of HRQoL assessments, all of which limit the strength of any conclusions. There is no consensus on the optimal transfusion regimen to improve HRQoL in transfusion-dependent MDS. Future research into HRQoL within MDS is a pressing requirement. Studies should focus on the domains that are of most clinical importance to the patient as well as traditional quantitative changes of hemoglobin concentration.

Serious hazards of transfusion: a decade of hemovigilance in the UK.

The Serious Hazards of Transfusion (SHOT) scheme is a UK-wide, independent, professionally led hemovigilance system focused on learning from adverse events. SHOT was established in 1996 as a confidential reporting system for significant transfusion-related events, building an evidence base to support blood safety policy decisions, clinical guidelines, clinician education, and improvements in transfusion practice. Recommendations are formulated by an independent steering group drawn from medical royal colleges and professional bodies. Ten years after its inception, SHOT has analyzed 2630 transfusion safety events, published 8 annual reports with recommendations, and presented data nationally and internationally. These recommendations have underpinned key initiatives, in particular the UK Department of Health "Better Blood Transfusion" strategy. SHOT has encouraged open reporting of adverse events and "near-misses" in a supportive, learning culture, vigilance in hospital transfusion practice, and evaluation of information technology to support this process. The importance of education and training has been emphasized. Detailed analysis of events has identified weaknesses in the transfusion chain. A collaborative initiative between SHOT, the Chief Medical Officer for England's National Blood Transfusion Committee, and the National Patient Safety Agency aims to reduce ABO-incompatible transfusions by improving bedside practice. Cumulative SHOT data have documented the decline in transfusion-related graft vs host disease after implementation of leucodepletion and have highlighted transfusion-related acute lung injury and bacterial contamination of platelets as important causes of death and morbidity. The UK blood services have developed strategies to reduce these risks. Future SHOT data will evaluate the success of these and other blood safety improvements.

Do all patients with hematologic malignancies and severe thrombocytopenia need prophylactic platelet transfusions? Background, rationale, and design of a clinical trial (trial of platelet prophylaxis) to assess the effectiveness of prophylactic platelet transfusions.

Although considerable advances have been made in many aspects of platelet transfusion therapy in the last 30 years, some areas continue to provoke debate, including the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding in patients with bone marrow failure. We have designed a randomized controlled trial to compare prophylactic platelet use with a threshold of a platelet count of 10 x 10(9)/L with no prophylaxis in adult thrombocytopenic patients with hematologic malignancies. The trial question is whether a no-prophylactic policy for the use of platelet transfusions in patients with hematologic malignancies is not inferior to a threshold prophylactic policy at 10 x 10(9)/L, for bleeding at World Health Organization (WHO) grade 2, 3, or 4, up to 30 days from randomization. The primary outcome measure is the proportion of patients who have a significant clinical bleed, defined as WHO grade 2 or higher up to 30 days from randomization. Subsidiary clinical outcome measures include time to first bleed and a descriptive analysis of all severe bleeds. A bleeding assessment form is completed daily for all study subjects until day 30 from randomization. Minor modifications were made to the definitions at WHO grades 1 and 2 for petechiae and duration of nose bleeds, after piloting of the bleeding assessment forms. This study has been designed as a 2-stage randomized trial with an interim analysis planned after a minimum of 100 patients had been randomized and had completed their period of observation. Patients have initially been enrolled through 3 United Kingdom hematology centers. The interim analysis has been completed, and the results have confirmed a final sample size of 600 patients. Recruitment is now being extended to other centers in United Kingdom and Australia. Local research nurses are not blinded to treatment allocation, but a number of measures to reduce risk of assessment bias include repeated education around standard operating procedures, common definitions, and duplication of assessments. The expected completion date for the 5-year study is December 2011.