David Roxby

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion

The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies.

Experience with a massive transfusion protocol in the management of massive haemorrhage

A massive transfusion response (MTR) was introduced in 2007 to provide blood and blood products in a timelier manner. Aim of this study was to determine whether implementation of the MTR was associated with a change in clinical practice or mortality.

A ‘Dangerous’ Group O Donor: Severe Hemolysis in All Recipients of Organs from a Donor with Multiple Red Cell Alloantibodies

Alloimmune hemolysis is a recognized but infrequent complication of solid organ transplantation, particularly where there is incompatibility within the ABO blood group system. We describe severe hemolysis due to passenger lymphocyte syndrome (PLS) in all three recipients of organs from a single donor with multiple red cell (RC) alloantibodies. The first patient, a liver transplant recipient, required augmentation of immunosuppression to treat immune hemolysis due to anti‐B, ‐D, ‐C and ‐Cellano (k). This is the first description of PLS caused by alloantibody to the high incidence RC antigen, k. The two single lung transplant recipients developed hemolysis due to anti‐D. Both required escalation of immunosuppression and early transfusion support. Three months posttransplant, all three patients have ongoing evidence of compensated hemolysis. This series highlights the potential for severe non‐ABO‐mediated immune hemolysis following solid organ transplantation. A positive donor RC antibody screen should prompt careful monitoring of organ recipients for hemolysis.

A novel GATA1 mutation (Stop414Arg) in a family with the rare X-linked blood group Lu(a-b-) phenotype and mild macrothrombocytic thrombocytopenia.

116, 140–143. Raanani, P., Trakhtenbrot, L., Rechavi, G., Rosenthal, E., Avigdor, A., Brok-Simoni, F., Leiba, M., Amariglio, N., Nagler, A. & Ben-Bassat, I. (2005) Philadelphia-chromosome-positive Tlymphoblastic leukemia: acute leukemia or chronic myelogenous leukemia blastic crisis. Acta Haematologica, 113, 181–189. Vardiman, J.W., Thiele, J., Arber, D.A., Brunning, R.D., Borowitz, M.J., Porwit, A., Harris, N.L., Le Beau, M.M., Hellstrom-Lindberg, E., Tefferi, A. & Bloomfield, C.D. (2009) The 2008 revision of the world health organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937–951.

Detection of the Tn antigen in leukaemia using monoclonal anti-Tn antibody and immunohistochemistry.

Exposure of the normally cryptic Tn antigen on haemopoietic cells leading to erythrocyte polyagglutination has been reported in a few cases of malignant or premalignant haemopoietic disorders and has been attributed to a selective deficiency of the enzyme 3–β‐D‐galactosyl‐transferase, A male patient presented with acute myelomonocytic leukaemia with no evidence of Tn expression but, 16 months later, in the terminal stage of the disease, the majority of the erythrocytes were found to be polyagglutinable. Tn expression was confirmed by the use of lectins and by agglutination with a Tn‐specific monoclonal antibody. FBT3. Retrospective studies of stored blood and bone marrow smears were performed by immunocytochemistry using FBT3. Tn positive cells were first detected in the marrow 8 months prior to death. They increased progressively in number and, in the terminal illness, over 90% of erythroid precursors in the marrow and erythrocytes in peripheral blood and 40% of granulocyte precursors of the marrow and 10% of granulocytes in the blood were Tn positive. These observations suggest that Tn expression was present in a subclone of cells which became dominant during the course of the disease and that there may be a relationship between Tn expression and leukaemic progression.

Mortality outcomes in patients transfused with fresher versus older red blood cells: a meta-analysis

Among transfused patients, the effect of the duration of red blood cell storage on mortality remains unclear. This study aims to compare the mortality of patients who were transfused with fresher versus older red blood cells.

Change in transfusion practice in massively bleeding patients.

This retrospective study evaluates changes in transfusion practice and modified blood product utilisation that occurred over the course of eleven years in patients receiving massive transfusion. The mean number of fresh frozen plasma units transfused increased from 9.0 ± 7.9 in 1998 to 11.3 ± 6.7 in 2008 (p=0.03). The mean number of platelet units increased from 1.9 ± 1.3 in 1998 to 2.6 ± 1.7 in 2008 (p=0.02). The proportion of cryoprecipitate increased from 0.03 ± 0.19 in 1998 to 1.3 ± 1.6 in 2008 (p=0.001). Along with these changes was a trend toward decreased mortality (p=0.05).

Pure anti-Doa stimulated by pregnancy

Pure anti‐Doa stimulated by pregnancy was detected in 2 non‐transfused females during routine antenatal screening. Anti‐Doa occurs rarely and has generally been reported in combination with other antibodies. The first, and only report to date, of pure anti‐Doa was also stimulated by pregancy. We believe these instances to be only the second and third reported cases of pure anti‐Doa.

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. If the results of INFORM indicate that shorter storage red blood cell transfusion is associated with superior outcomes compared with standard issue red blood cell transfusion, consideration may be given to shortening blood storage times. If, in contrast, the INFORM trial provides no evidence of harm from longer storage red blood cells, clinicians and patients may be reassured that current blood inventory management strategies are appropriate.

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. Patients were randomly assigned (2:1) to receive blood in inventory stored for the longest time (standard care) or the shortest time, using a random allocation schedule and stratified by centre and patient ABO blood group. The primary objective of the INFORM trial was to assess all-cause in-hospital mortality in patients with blood group A and O who were transfused. For our exploratory secondary analysis, we classified individuals into one of three mutually exclusive exposure categories on the basis of the maximum storage duration of any blood unit patients had received on each day in hospital: exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored longer than 35 days. Our primary objective was to determine the effect on risk of in-hospital death of time-dependent exposure to RBCs stored longer than 35 days compared with exclusive exposure to RBCs stored no longer than 7 days, both in patients of blood groups A and O and all patients. The INFORM trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN08118744. FINDINGS Between April 2, 2012, and Oct 21, 2015, 31 497 patients were recruited, and 24 736 patients were eligible for inclusion in this analysis. We excluded nine patients for whom information about the storage duration of transfused blood was missing and one patient whose sex was unknown. 4480 (18%) patients were exposed to RBCs with longest storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20). Exposure to RBCs stored longer than 35 days was not associated with increased risk of in-hospital death compared with exclusive exposure to the freshest RBC units after adjusting for demographic variables, diagnosis category, and blood product use history (in patients with blood group A or O: hazard ratio 0·94, 95% CI 0·73-1·20, p=0·60; in all patients: 0·91, 0·72-1·14, p=0·40). The risk of in-hospital death also did not differ between patients exposed to blood stored 8-35 days and patients exposed to blood stored 7 days or less (in patients with blood group A or O: 0·92, 0·74-1·15, p=0·48; in all patients: 0·90, 0·73-1·10, p=0·29). INTERPRETATION These data provide evidence that transfusion of blood stored for longer than 35 days has no effect on in-hospital mortality, which suggests that current approaches to blood storage and inventory management are reasonable. FUNDING Canadian Institutes for Health Research, Canadian Blood Services, and Health Canada.