Transfusion-associated circulatory overload prevention: a retrospective observational study of diuretic use.

BACKGROUND AND OBJECTIVES: Approaches to preventing transfusion-associated circulatory overload (TACO) include the use of diuretics. The purpose of this study was to determine how commonly diuretics are prescribed in patients receiving a red-blood-cell (RBC) transfusion. MATERIALS AND METHODS: This was a retrospective study of 200 adult inpatient RBC transfusion orders, 50 consecutive at each of four academic institutions. Only the first transfusion order for each patient was included. Only 1 or 2 unit orders were included. The primary outcome was the percentage of patients receiving furosemide peri-transfusion. Secondary objectives included the dose, route, and timing of furosemide and the association of clinical factors with ordering furosemide. RESULTS: The median age was 62·5 years (IQR 53, 73), and 52% were female. Peri-transfusion furosemide was ordered in 16% (95% CI 11-21%). The most common dose was 20 mg (55%), the route intravenous (90%) and timing post-transfusion (74%). At least one risk factor for TACO was present in 55% of patients: renal dysfunction (33%), older than 70 years (28%), history of congestive heart failure (18%), ejection fraction <60% (16%) and diastolic dysfunction (5%). Low haemoglobin as an indication for transfusion (OR 4·2; 95% CI 1·4-12·8) and diuretics on admission (OR 3·5; 95% CI 1·5-8·0) were associated with ordering furosemide peri-transfusion. CONCLUSIONS: Furosemide is not routinely ordered for RBC transfusion, even in patients with risk factors for TACO. Studies assessing the safety, efficacy, optimal dose, and timing of furosemide in preventing TACO are justified.

Audit of appropriate use of platelet transfusions: validation of adjudication criteria.

BACKGROUND AND OBJECTIVES: Platelet (PLT) transfusions must be used appropriately, as they are in chronic short supply, costly and risky to patients. The goals of this audit were to: (1) validate preset adjudication criteria through an audit of appropriateness at four large academic hospitals; (2) identify variability in appropriateness across medical services, physician specialties or hospital locations; and (3) inform logistical or educational interventions that may reduce inappropriate use. MATERIALS AND METHODS: A chart review of two hundred patients receiving PLT transfusions was performed. Fifty consecutive transfusion episodes per site were audited in detail. Each transfusion episode was independently adjudicated as appropriate or inappropriate by two transfusion specialists based on predetermined criteria. RESULTS: The adjudication criteria performed well with simple agreement of 95% (kappa statistic 0·83) between reviewers. Overall, 78% (95% CI: 72-84%) of PLT transfusions were adjudicated as appropriate, with results varying significantly by hospital site (range 62-94%). Prophylactic transfusions for non-bleeding patients had the highest proportion of appropriateness (85%, n = 80), and therapeutic transfusions for bleeding patients had the lowest (73%, n = 99). The lowest levels of appropriate platelet transfusions were observed in the operating rooms (60%) and when ordered by the general surgery service (55%). CONCLUSIONS: One in five platelet transfusions may be unnecessary, suggesting that interventions to improve PLT transfusion practice are warranted.

The association of fever with transfusion-associated circulatory overload.

BACKGROUND: Fever is described in transfusion-associated circulatory overload (TACO), reflecting either comprehensive haemovigilance or an inflammatory pathobiology (such as congestion-associated atheroma disruptions). METHODS: Hospital haemovigilance data (1/1/2010-31/12/2012) were reviewed for TACO cases (frequency and mode of referral). TACO with or without fever (TACO+F/-F) was examined for its association with patient age (as a surrogate for atheroma burden) and product age (as a surrogate for storage-related pyrogens). Fever in allergic transfusion reactions was also compared. RESULTS: Of 972 reactions, 107 suspected cases of TACO (11%) were seen. TACO+F vs. TACO-F occurred in 42·1 vs. 57·9%, respectively. TACO+F cases were discovered in referrals to investigate either a fever (in 47·1%) or dyspnoea (in 52·9%). Among TACO+F cases, 24·4% had already been febrile, whereas 75·6% exhibited a new reaction-associated fever. After excluding preexisting fevers, TACO+F occurred in 31·8% of TACO, compared with 8·2% of allergic reactions with fever, for an odds ratio of 5·2 (2·9-9·4 [95% CI]), P < 0·001. TACO+F/TACO-F showed no difference in median host age (69 vs. 64 years, P = 0·3), RBC age (22 days +F/-F, P = 0·9) or severity. CONCLUSION: Transfusion-associated circulatory overload disproportionately exhibits fever compared with allergic reactions. However, TACO+F did not associate with patient or product age, nor reflect severity. To better understand TACO+F, the fever-congestion sequence merits attention. Further study is needed to see whether TACO+F occurs as reproducibly elsewhere, and in association with atherosclerosis in a better characterized cohort.

Red cell transfusion and the immune system.

Understanding the complex immunological consequences of red cell transfusion is essential if we are to use this valuable resource wisely and safely. The decision to transfuse red cells should be made after serious considerations of the associated risks and benefits. Immunological risks of transfusion include major incompatibility reactions and transfusion-related acute lung injury, while other immunological insults such as transfusion-related immunomodulation are relatively underappreciated. Red cell transfusions should be acknowledged as immunological exposures, with consequences weighed against expected benefits. This article reviews immunological consequences and the emerging evidence that may inform risk-benefit considerations in clinical practice.

Plasmodium falciparum malaria and the immunogenetics of ABO, HLA, and CD36 (platelet glycoprotein IV).

Plasmodium falciparum malaria has long been a killer of the young, and has selected for polymorphisms affecting not only erythrocytes, but the immunogenetics of three histocompatibility systems: ABO, human leukocyte antigen (HLA), and CD36. The ABO system is important because the original allele, encoding glycosylation with the A sugar, acts as an adhesion ligand with infected red blood cells (iRBC), thereby promoting vasoocclusion. The prevalence of blood group O, which reduces this cytoadhesion, has increased in endemic areas. Other adaptations which could mitigate A-mediated rosetting include weaker A expression and increased soluble A secretion. The role of the HLA system in malaria has been harder to verify. Although HLA-B53 and DRB1*04 may be associated with clinical outcome, HLA studies are challenged by numerous comparisons in this most polymorphic of systems, and confounded by increasingly heterogeneous populations. Certain HLA markers may also reflect linkage artefact with other malaria-relevant polymorphisms. HLA may be less important because the parasite predominantly invades a compartment which does not express HLA. Adhesion of iRBCs is also mediated by CD36, expressed on platelets, monocytes, and microvascular endothelium. CD36 on monocytes is involved in clearing iRBC, while CD36 on platelets and the endothelium may play a role in tissue sequestration. The genetics of CD36 expression are complex, and recent research is fraught with inconsistent results. The solution may lie in examining genotype-phenotype correlations, zygosity effects on differential tissue expression, or other mechanisms altering CD36 tissue expression. Carefully designed prospective studies should bridge the gap between in-vitro observations and clinical outcomes.

Platelet transfusion refractoriness responding preferentially to single donor aphaeresis platelets compatible for both ABO and HLA.

Platelet transfusion refractoriness is challenging to manage. When human leucocyte antigens (HLA)-sensitized patients fail to respond to HLA-matched (HLA-m) platelets, non-immune destruction may be assumed, and collections of HLA-m platelets abandoned. We report cases of highly HLA-sensitized patients whose only satisfactory platelet transfusion responses were consistently associated with products compatible for both HLA- and ABO-matched (HLA-m/ABO-m) platelets, and in whom unsatisfactory increments occurred if either form of major incompatibility was permitted (HLA-u or ABO-u). Absolute platelet increments (APIs) were measured and classified as satisfactory if ≥10 and unsatisfactory if <10. Patient 1, age 59 years, group O, with myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML), was unresponsive to either fresh ABO-m or HLA-m platelets. Of 17 HLA-m platelets, satisfactory responses occurred for 75% of HLA-m/ABO-m units, and failures for 100% of HLA-m/ABO-u, with mean API differing significantly (14·1 vs 1·1, P = 0·0059). Of 36 HLA-m platelets given to patient 2, age 49 years, group O, Gravida 2 Para 2, with severe aplastic anaemia, a satisfactory response occurred with 75% of HLA-m/ABO-m units, and failures for 63% of the HLA-m/ABO-u (mean API 26·7 vs 7·6, P = 0·008). Increment failures from HLA-m platelets need not imply intractable refractoriness. If resources permit, selection of HLA-m/ABO-m platelets may optimise the incremental response.

When monocytes and platelets compete: The effect of platelet count on the flow cytometric measurement of monocyte CD36.

BACKGROUND: Flow cytometric measurement of monocyte surface CD36 is relevant to several conditions including diabetes, cardiovascular disease, lipid disorders, platelet isoimmunization, and susceptibility to P falciparum malaria. CD36 is also strongly expressed on platelets where it is also known as platelet glycoprotein IV. METHODS: Whole blood samples, containing identical monocyte concentrations, were adjusted to contain platelets ranging from 20,000/uL to 600,000/uL, were stained with fluorescent-labeled anti-CD36, and analyzed by flow cytometry. RESULTS: CD36 median fluorescent intensity (MFI) observed on monocytes decreased as the platelet concentration in the sample increased with more than a 50% decline in monocyte MFI over the normal range of platelet values. The effect was not abolished by using larger volumes of monoclonal antibody and was observed with different clones of reagent anti-CD36. The findings were most consistent with competition by platelets for the CD36 reagent. Similar findings were observed with antibody to class I HLA. Under defined assay conditions, monocyte CD36 MFI declined with rising platelet concentration in a predictable fashion following an inverse linear relationship. CONCLUSIONS: Measurement of CD36 expression on monocytes by flow cytometry in whole blood samples is affected by the sample platelet count. When comparing the monocyte CD36 expression among different individuals, our approach can be used to adjust measured monocyte CD36 expression for the effect of the platelet concentration in the sample. Competition by platelets for monoclonal reagents may occur in other settings when whole blood assays are used and when the target antigen is strongly expressed on both platelets and leukocytes.