Erica M. Wood

An update of consensus guidelines for warfarin reversal.

For most warfarin indications, the target international normalised ratio (INR) is 2.0–3.0 (venous thromboembolism and single mechanical heart valve excluding mitral). For mechanical mitral valve or combined mitral and aortic valves, the target INR is 2.5–3.5. Risk factors for bleeding with warfarin use include increasing age, history of bleeding and specific comorbidities. For patients with elevated INR (4.5–10.0), no bleeding and no high risk of bleeding, withholding warfarin with careful subsequent monitoring seems safe. Vitamin K1 can be given to reverse the anticoagulant effect of warfarin. When oral vitamin K1 is used for this purpose, the injectable formulation, which can be given orally or intravenously, is preferred. For immediate reversal, prothrombin complex concentrates (PCC) are preferred over fresh frozen plasma (FFP). Prothrombinex‐VF is the only PCC routinely used for warfarin reversal in Australia and New Zealand. It contains factors II, IX, X and low levels of factor VII. FFP is not routinely needed in combination with Prothrombinex‐VF. FFP can be used when Prothrombinex‐VF is unavailable. Vitamin K1 is essential for sustaining the reversal achieved by PCC or FFP. Surgery can be conducted with minimal increased risk of bleeding if INR ≤ 1.5. For minor procedures where bleeding risk is low, warfarin may not need to be interrupted. If necessary, warfarin can be withheld for 5 days before surgery, or intravenous vitamin K1 can be given the night before surgery. Prothrombinex‐VF use for warfarin reversal should be restricted to emergency settings. Perioperative management of anticoagulant therapy requires an evaluation of the risk of thrombosis if warfarin is temporarily stopped, relative to the risk of bleeding if it is continued or modified.

Age of red blood cells and mortality in the critically ill

IntroductionIn critically ill patients, it is uncertain whether exposure to older red blood cells (RBCs) may contribute to mortality. We therefore aimed to evaluate the association between the age of RBCs and outcome in a large unselected cohort of critically ill patients in Australia and New Zealand. We hypothesized that exposure to even a single unit of older RBCs may be associated with an increased risk of death.MethodsWe conducted a prospective, multicenter observational study in 47 ICUs during a 5-week period between August 2008 and September 2008. We included 757 critically ill adult patients receiving at least one unit of RBCs. To test our hypothesis we compared hospital mortality according to quartiles of exposure to maximum age of RBCs without and with adjustment for possible confounding factors.ResultsCompared with other quartiles (mean maximum red cell age 22.7 days; mortality 121/568 (21.3%)), patients treated with exposure to the lowest quartile of oldest RBCs (mean maximum red cell age 7.7 days; hospital mortality 25/189 (13.2%)) had an unadjusted absolute risk reduction in hospital mortality of 8.1% (95% confidence interval = 2.2 to 14.0%). After adjustment for Acute Physiology and Chronic Health Evaluation III score, other blood component transfusions, number of RBC transfusions, pretransfusion hemoglobin concentration, and cardiac surgery, the odds ratio for hospital mortality for patients exposed to the older three quartiles compared with the lowest quartile was 2.01 (95% confidence interval = 1.07 to 3.77).ConclusionsIn critically ill patients, in Australia and New Zealand, exposure to older RBCs is independently associated with an increased risk of death.

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors

Background Currently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency. Design and Methods Sera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzyme-linked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency. Results In 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20.4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2–199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%. Conclusions Serum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.

Detection of bacterial contamination of platelet concentrates.

R. N. I. Pietersz, C. P. Engelfriet, H. W. Reesink, E. M. Wood, S. Winzar, A. J. Keller, J. T. Wilson, G. Henn, W. R. Mayr, S. Ramírez-Arcos, M. Goldman, J. Georgsen, P. Morel, P. Herve, G. Andeu, A. Assal, E. Seifried, M. Schmidt, M. Foley, C. Doherty, P. Coakley, A. Salami, E. Cadden, W. G. Murphy, M. Satake, D. de Korte, V. Bosnes, J. Kjeldsen-Kragh, C. McDonald, M. E. Brecher, R. Yomtovian & J. P. AuBuchon

Reducing the risk of transfusion‐transmissible viral infection through blood donor selection: the Australian experience 2000 through 2006

BACKGROUND: Selection of voluntary donors who are at low risk of transfusion‐transmissible viral infection (TTVI) is central in maintaining the safety of the blood supply. Evaluation of its effectiveness and the dynamics of the process may offer opportunities to further improve transfusion safety.

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.

Cytomegalovirus in pregnancy: to screen or not to screen

BackgroundCytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented.DiscussionUniversal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients.SummaryWe suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease.

Impact of prophylactic platelet transfusions on bleeding events in patients with hematologic malignancies: a subgroup analysis of a randomized trial

A recent randomized trial compared a policy of no prophylaxis with a policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10 × 109/L in patients with hematologic malignancies. The results suggested the effectiveness of prophylactic PLT transfusions may vary according to patient diagnosis and treatment plan.

Establishment of the first International Repository for Transfusion‐Relevant Bacteria Reference Strains: ISBT Working Party Transfusion‐Transmitted Infectious Diseases (WP‐TTID), Subgroup on Bacteria

Background  Bacterial contamination of platelet concentrates (PCs) still remains a significant problem in transfusion with potential important clinical consequences, including death. The International Society of Blood Transfusion Working Party on Transfusion‐Transmitted Infectious Diseases, Subgroup on Bacteria, organised an international study on Transfusion‐Relevant Bacteria References to be used as a tool for development, validation and comparison of both bacterial screening and pathogen reduction methods.

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.