Kathryn E. Webert

Transfusion‐Related Acute Lung Injury

PURPOSE OF REVIEW Transfusion-related acute lung injury is an uncommon complication of blood transfusion typically manifested by shortness of breath, fever, and hypotension. Transfusion-related acute lung injury is an important cause of transfusion-related morbidity and mortality. RECENT FINDINGS Much about the pathogenesis, treatment, and prevention of transfusion-related acute lung injury is poorly understood or is controversial. There is increasing recognition that transfusion-related acute lung injury is an important clinical syndrome, causing most transfusion-related deaths. SUMMARY In this report, what is known about transfusion-related acute lung injury is summarized with particular emphasis on recent studies. Some of the areas in which knowledge and/or consensus are currently lacking are identified.

Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments.

Summary.  Background: Light transmission aggregometry (LTA) is commonly performed to assess individuals for bleeding disorders. Objectives: The goal was to evaluate the incidence and spectrum of platelet function abnormalities in a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. Patients/methods: Subjects were healthy controls and patients from a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. LTA was performed by standardized methods using platelet‐rich plasma adjusted to 250 × 109 platelets L−1. Maximal aggregation data were analyzed to determine the likelihood of detecting a platelet function disorder by LTA, and the sensitivity and specificity of LTA for platelet disorders. Results: The incidence of false positive LTA among subjects excluded of having bleeding disorders was similar to healthy controls. Abnormal LTA was more common in subjects with bleeding disorders and the likelihood of a bleeding disorder was significantly increased (odds ratio 32) when maximal aggregation was reduced with two or more agonists. Receiver operator curve analyses indicated that LTA had high specificity and moderate sensitivity for detecting inherited defects in platelet function and that the LTA agonists 1.25 μg mL−1 collagen, 6 μM epinephrine, 1.6 mM arachidonic acid and 1.0 μM thromboxane analogue U44619 detected most inherited disorders with abnormal LTA. Conclusions: LTA is valuable for detecting platelet function abnormalities among individuals referred for bleeding problems, particularly when the test indicates abnormal responses to multiple agonists.

Methodologic issues in the use of bleeding as an outcome in transfusion medicine studies

BACKGROUND: Prophylactic platelet transfusions are given to thrombocytopenic patients to prevent bleeding. The benefit of platelet transfusions has frequently been assessed by measuring the count increment; however, more recently, an assessment of bleeding has been used because it is a more clinically relevant outcome measure. The purpose of this study was to identify platelet transfusion trigger studies that used bleeding as an outcome measure, compare and contrast methods used to document bleeding and analyze bleeding outcomes, and identify and discuss methodologic issues to consider when bleeding is used as a study outcome.

Comparing the efficacy and safety of apheresis and whole blood-derived platelet transfusions : a systematic review

BACKGROUND: A systematic review and meta‐analysis was performed to determine if there were differences between apheresis platelet concentrates (APCs) or platelets (PLTs) derived from whole blood (WBD) for the outcomes acute reactions, alloimmunization, refractoriness, corrected count increment (CCI), radiolabeled recovery and survival, time to next transfusion, and bleeding.

An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts

Light transmission platelet aggregation tests are important for diagnosing platelet function defects. However, uncertainties exist about the best procedures to determine aggregation reference intervals. We investigated methods for determining reference intervals for light transmission aggregation tests, using the % maximal aggregation values for prospectively collected data on healthy control samples. Reference intervals for samples tested at 250 x 10(9) platelets/l were determined by mean +/- 2 standard deviations and non-parametric analyses. To establish reference intervals for tests on thrombocytopenic subjects, regression analyses were used to estimate 95% confidence limits for % maximal aggregation, according to sample platelet counts, using data for control samples diluted to match the platelet count of undiluted thrombocytopenic patient platelet-rich plasma samples. For samples tested at 250 x 10(9) platelets/l, non-parametric analyses described 95% of data for healthy control samples better than mean +/- 2 standard deviations. For samples tested at lower counts, to match thrombocytopenic samples, the % maximal aggregation was influenced by platelet count and derived limits were wider at very low platelet counts for almost all agonists. With ristocetin, it proved feasible to test samples with very low platelet counts to exclude Bernard-Soulier syndrome and type 2B von Willebrand disease. Non-parametric analyses should be the preferred method to establish light transmission aggregation reference intervals for samples tested at normal platelet counts. The derived limits for thrombocytopenic samples provide guidance for evaluating thrombocytopenic platelet function disorders, including which agonists to test, based on the sample platelet count.

The effect of blood storage duration on in-hospital mortality: a randomized controlled pilot feasibility trial

BACKGROUND: Whether the duration of storage of blood has an impact on patient outcomes remains controversial. The objective was to determine feasibility of a comparative effectiveness trial to evaluate duration of storage of blood before transfusion on in‐hospital mortality.

A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation

BACKGROUND: Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.

Transfusion-related acute lung injury.

Purpose of reviewTransfusion-related acute lung injury is an uncommon complication of blood transfusion typically manifested by shortness of breath, fever, and hypotension. Transfusion-related acute lung injury is an important cause of transfusion-related morbidity and mortality. Recent findingsMuch about the pathogenesis, treatment, and prevention of transfusion-related acute lung injury is poorly understood or is controversial. There is increasing recognition that transfusion-related acute lung injury is an important clinical syndrome, causing most transfusion-related deaths. SummaryIn this report, what is known about transfusion-related acute lung injury is summarized with particular emphasis on recent studies. Some of the areas in which knowledge and/or consensus are currently lacking are identified.

Diagnostic Usefulness of a Lumi-Aggregometer Adenosine Triphosphate Release Assay for the Assessment of Platelet Function Disorders

Platelet dense granule release assays are recommended for diagnosing platelet function disorders and are commonly performed by Lumi-Aggregometer (Chrono-Log, Havertown, PA) assays of adenosine triphosphate (ATP) release. We conducted a prospective cohort study of people tested for ATP release defects to assess bleeding symptoms. Reduced release, with 1 or more agonists, was more common among patients with bleeding disorders than among healthy control subjects (P < .001). The respective likelihood (odds ratio [95% confidence interval]) of a bleeding disorder or an inherited platelet function disorder were high when release was reduced with 1 or more agonists (17 [6-46]; 128 [30-545]), even if aggregation was normal (12 [4-34]; 105 [20-565]). ATP release had high specificity and moderate sensitivity for inherited platelet function disorders, with most abnormalities detected by the combination of 6 μmol/L epinephrine, 5.0 μg/mL collagen, and 1 μmol/L U46619. Platelet ATP release assays are useful for evaluating common bleeding disorders, regardless of aggregation findings.

Hypotensive transfusion reactions can occur with blood products that are leukoreduced before storage.

BACKGROUND:  Leukoreduction before storage, rather than bedside white blood cell filtration, is recommended to prevent hypotensive transfusion reactions.