Debra Masel

An association between decreased cardiopulmonary complications (transfusion-related acute lung injury and transfusion-associated circulatory overload) and implementation of universal leukoreduction of blood transfusions.

BACKGROUND: Cardiopulmonary adverse events after transfusion include transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO), which are potentially lethal and incompletely understood.

The role of ABO matching in platelet transfusion

Abstract:  A prospective controlled trial was performed to determine whether the use of ABO‐identical platelets from the start of treatment might provide higher post‐transfusion platelet increments, reduce the number of platelet transfusions and ultimately delay the onset of refractoriness. Forty newly diagnosed patients with haematological diseases were randomized to receive either pooled ABO‐identical platelets or pooled platelets unmatched for ABO group throughout their course. The corrected platelet count increments (CCI) were calculated for the first 25 transfusions of each patient and non‐immune factors present at the time of each platelet transfusion were documented. The mean CCI for the first 25 transfusions in the ABO‐identical group was significantly higher (6600 ±: 7900 SD) than that achieved with ABO unmatched platelets (5200 ±: 7900; p<0.01). The effect was most marked for the first 10 transfusions for each patient where the CCI was 64% higher in the ABO‐identical group (8200 ±: 7500 vs 5000 ±: 8100; p<0.0002). Patients given ABO‐identical platelets required only about half as many transfusions in the first 30 days (10 versus 17, p<0.05) or during the first admission (11 versus 21 p<0.01) as patients in the ABO‐unmatched group. A smaller percentage of patients in the ABO‐identical group became refractory (36% vs 75% p<0.03). The data suggest that patients requiring long‐term platelet support should be transfused with ABO‐identical platelets.

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi‐site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA‐based selection. Seventy‐three patients who were refractory to random‐donor platelets received two plateletpheresis components, one chosen by HLA‐based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA‐based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch‐based method of donor selection. 2) HLA‐based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA‐ cross‐reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA‐ compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch‐selected platelets are acceptable as an alternative component.

Circulating immune complexes involving the ABO system after platelet transfusion

Summary. It has been proposed that when ABO unmatched platelets are transfused circulating immune complexes (CIC) may be formed between the patients soluble ABH antigens and the transfused antibodies. Platelets might then be destroyed by bystander mechanisms or by the binding of CIC to the Fc receptor or to C3 binding membrane proteins on the platelet. An ELISA Clq assay was used to detect CIC in 40 patients with haematological diseases who had received multiple platelet transfusions. A significantly larger number of refractory patients were positive (41%) in the assay than non‐refractory patients (13%) or normal blood donors (0%). The presence of circulating IgG anti‐A was sought in six group A refractory patients who had been transfused with ABO unmatched platelets. To determine whether the IgG anti‐A was monomeric or in high molecular weight complexes, the serum was fractionated by gel exclusion chromatography and fractions were tested for the presence of IgG anti‐A. In all six patients the peak of IgG anti‐A binding occurred in fractions of high molecular weight (200–900 kD). Five out of six patients also demonstrated anti‐A activity in fractions corresponding to monomeric IgG (about 150–180 kD). Fractions containing high molecular weight anti‐A were purified using a protein G column and the eluates were tested for the presence of group A antigen using dot immunoblotting. Group A antigen was associated with the purified IgG anti‐A in 4/5 patients tested. Appropriate transfused and non‐transfused controls had no anti‐A in any fractions. Although not unexpected, these studies demonstrate for the first time that refractory patients receiving ABO unmatched platelets have CIC composed of ABO antigens and their corresponding antibodies present in their serum that circulate for at least several days. It also confirms the hypothesis that some CIC in haematological patients are induced by transfusion.

Antibodies to plasma proteins: an association with platelet transfusion refractoriness

Summary. We hypothesized that antibodies to HLA‐linked polymorphic plasma proteins could be involved in platelet refractoriness by an‘innocent bystander’or immune complex mechanism. Employing a kinetic enzyme‐linked immunosorbant assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti‐plasma protein antibody could be eluted from platelets of refractory patients.

Transfusion of cell saver salvaged blood in neonates and infants undergoing open heart surgery significantly reduces RBC and coagulant product transfusions and donor exposures: results of a prospective, randomized, clinical trial

Objective: To evaluate whether transfusion of cell saver salvaged, stored at the bedside for up to 24 hrs, would decrease the number of postoperative allogeneic RBC transfusions and donor exposures, and possibly improve clinical outcomes. Design: Prospective, randomized, controlled, clinical trial. Setting: Pediatric cardiac intensive care unit. Patients: Infants weighing less than 20 kg (n = 106) presenting for cardiac surgery with cardiopulmonary bypass. Interventions: Subjects were randomized to a cell saver transfusion group where cell saver blood was available for transfusion up to 24 hrs after collection, or to a control group. Cell saver subjects received cell saver blood for volume replacement and/or RBC transfusions. Control subjects received crystalloid or albumin for volume replacement and RBCs for anemia. Blood product transfusions, donor exposures, and clinical outcomes were compared between groups. Measurements and Main Results: Children randomized to the cell saver group had significantly fewer RBC transfusions (cell saver: 0.19 ± 0.44 vs. control: 0.75 ± 1.2; p = 0.003) and coagulant product transfusions in the first 48 hrs post-op (cell saver: 0.09 ± 0.45 vs. control: 0.62 ± 1.4; p = 0.013), and significantly fewer donor exposures (cell saver: 0.60 ± 1.4 vs. control: 2.3 ± 4.8; p = 0.019). This difference persisted over the first week post-op, but did not reach statistical significance (cell saver: 0.64 ± 1.24 vs. control: 1.1 ± 1.4; p = 0.07). There were no significant clinical outcome differences. Conclusion: Cell saver blood can be safely stored at the bedside for immediate transfusion for 24 hrs after collection. Administration of cell saver blood significantly reduces the number of RBC and coagulant product transfusions and donor exposures in the immediate postoperative period. Reduction of blood product transfusions has the potential to reduce transfusion-associated complications and decrease postoperative morbidity. Larger studies are needed to determine whether this transfusion strategy will improve clinical outcomes.

Providing ABO‐identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence

BACKGROUND: There are multiple benefits to transfusing only ABO‐identical blood components. Historically our institution routinely transfused ABO‐nonidentical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO‐identical components whenever feasible, regardless of outdating or logistic considerations.

Interaction of Platelet Fc and Complement Receptors with Circulating Immune Complexes Involving the AB0 System

When platelets that are AB0‐nonidentical are transfused, circulating immune complexes (CIC) are formed. In the present study we examined the ability of polyclonal antibodies to two C1q receptors on platelets, cC1q‐R and gC1q‐R, and a monoclonal IgG FcγRII (CD32) antibody directed against the platelet Fc receptor to inhibit the uptake of CIC involving the AB0 blood group system by normal platelets. Four types of immune complexes of varying purity were made in vitro. In addition serum from 5 refractory group A patients who had demonstrable AB0 CIC, 5 patients who had received only AB0‐identical platelets and had no AB0 CIC and 6 normal donors were evaluated. After exposure of normal platelets to serum of patients with demonstrable AB0 CIC there were increased levels of platelet‐associated IgG. This binding was partially inhibited by preincubation of the platelets with either anti‐cC1q‐R (3/5 patients), gC1q‐R (3/5 patients) or IgG FcγRII in 4/5 patients. However, the pattern of inhibition by the three antibodies was variable. Using the artificial immune complexes a more consistent pattern was obtained. The binding of four types of artificial immune complexes to platelets was reduced by 67–99% after preincubation of the platelets with antibodies to the complement and Fc receptors. The present work supports the hypothesis that AB0 CIC bind to Fc and complement receptors on the platelet and if confirmed would suggest a pathophysiological mechanism for the clinical observations of the important role of AB0 in platelet transfusion.

An alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab.

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A chloroquine elution technique for platelet serology

The authors describe a prototype elution method employing chloroquine, a quinoline derivative, to elute IgG antibodies from the platelet surface. This chloroquine elution technique is relatively easy to perform and is effective in the removal of alloantibodies from the platelet surface. Eluted alloantibody was immunologically active once the chloroquine was removed from the eluate. The major advantage of this technique is that serologic testing of platelets after elution is possible, as 50 percent of the platelets remain after exposure to hypertonic acid chloroquine solution. Antigens on the platelet surface maintained their antigenicity subsequent to treatment, although measurable reductions in PIA1 reactivity occur. The elution technique was also successful in removing IgG from the platelet surface in patients with diseases involving elevated levels of platelet‐associated IgG.