Barbara Hannach

Fatal false-negative transfusion infection involving a buffy coat platelet pool contaminated with biofilm-positive Staphylococcus epidermidis: a case report.

Bacterial contamination of platelet concentrates (PCs) poses the major posttransfusion infectious risk in developed countries. The aerobic microorganism most frequently isolated from PCs is coagulase‐negative Staphylococcus epidermidis, a normal inhabitant of the human skin, which has been involved in fatal transfusion reactions worldwide.

Monoclonal antibody‐mediated inhibition of the human HLA alloimmune response to platelet transfusion is antigen specific and independent of Fcγ receptor‐mediated immune suppression

Presensitization of donor platelets with allo‐specific immunoglobulin (Ig)G results in a diminished immune response against subsequent transfusions of platelets. To understand better the mechanism of how alloantibody presensitization results in a decreased alloimmune response, we have used murine monoclonal antibodies directed to polymorphic and non‐polymorphic regions of human leucocyte antigen (HLA) as well as platelet‐specific molecules. Here, we demonstrated that presensitization with anti‐human HLA class I antibodies, as well as β2‐microglobulin‐specific antibody, protected against alloantibody production to five subsequent untreated platelet challenges. Use of complement fixing, non‐fixing or F(ab′)2 fragments of HLA‐specific antibody also resulted in complete inhibition of alloantibody production. This protection was not seen when the platelets were presensitized with monoclonal antibodies to CD42a (GPIX), CD32 (low‐affinity IgG/Fcγ receptor) or murine IgG and was thus independent of B‐cell FcγRII‐mediated immune suppression. The inhibition observed was independent of HLA alloantigenic specificity as antibodies directed at the β2‐microglobulin portion of HLA class I were as effective as antibodies against any of the HLA‐α regions (either polymorphic or non‐polymorphic) of class I. This work demonstrates that monoclonal antibody‐mediated suppression of the human HLA alloimmune response to platelet transfusion is antigen specific and is independent of FcγRII‐mediated immune regulation, complement fixing or HLA alloantigenic specificity.

Induction of a secondary human anti-HLA alloimmune response in severe combined immunodeficient mice engrafted with human lymphocytes

BACKGROUND: Experimental manipulation of transfusion‐induced alloimmunization is limited in humans by ethical considerations. Conversely, studies of alloimmunization in animal models may not reflect the human immune system closely enough to be of optimal benefit. The development of an in vivo model of human alloimmunization that is amenable to experimental manipulation is thus desirable. STUDY DESIGN AND METHODS: An in vivo model of human alloimmunization was evaluated by using mice with severe combined immunodeficiency (SCID). SCID mice underwent gamma‐radiation (200 cGy) and received an intraperitoneal injection of human peripheral blood lymphocytes (PBLs) from donors immunized to HLA antigens by prior pregnancy (reconstitution). These Hu [human]‐PBL‐SCID mice were then challenged with HLA‐mismatched PBLs. Alloantibodies were evaluated by flow cytometry and a standard two‐stage microlymphocytotoxicity assay. RESULTS: Hu‐PBL‐SCID mice (n = 22) that were challenged with PBLs expressing the HLA antigens to which the donors had previously been immunized, made significantly more IgM and IgG alloantibodies than did the unchallenged mice. Responses were measurable by 1 week after reconstitution and challenge. Prior treatment of SCID mice with anti‐ asialo GM1, which depletes murine natural killer cells and macrophages, further increased the alloantibody response of challenged mice. The human alloantibodies generated were specific to the challenge HLA antigens as assessed by microlymphocytotoxicity assay. CONCLUSION: Hu‐ PBL‐SCID mice are a useful model system in which to study and manipulate the induction of secondary human alloimmune responses against cellular HLA class I antigens. This model will be valuable for testing the in vivo effect of novel immunotherapies on the inhibition of the human alloantibody response.

Antibody‐mediated inhibition of the human alloimmune response to platelet transfusion in Hu‐PBL‐SCID mice

Severe combined immune deficient (SCID) mice were engrafted with human (Hu) peripheral blood lymphocytes (PBL) from a previously alloimmunized donor and transfused with HLA‐mismatched platelets. We have previously shown this to be a useful model for platelet transfusion. These engrafted mice (Hu‐PBL‐SCID mice) produced high levels of alloantibody in response to standard platelet preparations. However, when the first platelet challenge was presensitized with anti‐HLA antibody and then transfused there was a marked reduction in the amount of alloantibody produced to five subsequent untreated platelet transfusions. Platelets pretreated with platelet‐specific anti‐HPA‐1a (PLA1) sera did not induce a decrease in the anti‐HLA alloantibody response. This demonstrated that platelet‐induced HLA alloimmunization can be blocked by anti‐HLA antibody‐sensitized cells.

Inhibition of a secondary human alloimmune response via the soluble active component of CD154 (CD40L) in severe combined immune‐deficient mice engrafted with human lymphocytes

BACKGROUND: Alloimmunization requires a process known as co‐stimulation. An important co‐stimulatory pathway for most immune responses is mediated by the interaction of CD40 on antigen‐presenting cells with CD154 (CD40L) on host T cells. Blockade of this co‐stimulatory pathway simultaneous with exposure to challenge with HLA‐incompatible cells is hypothesized to inhibit alloimmunization.

Perioperative transfusion-related acute lung injury: the Canadian Blood Services experience.

PURPOSE Transfusion-related acute lung injury (TRALI) is a devastating transfusion-associated adverse event. There is a paucity of data on the incidence and characteristics of TRALI cases that occur perioperatively. We classified suspected perioperative TRALI cases reported to Canadian Blood Services between 2001 and 2012, and compared them to non-perioperative cases to elucidate factors that may be associated with an increased risk of developing TRALI in the perioperative setting. METHODS All suspected TRALI cases reported to Canadian Blood Services (CBS) since 2001 were reviewed by two experts or, from 2006 to 2012, the CBS TRALI Medical Review Group (TMRG). These cases were classified based on the Canadian Consensus Conference (CCC) definitions and detailed in a database. Two additional reviewers further categorized them as occurring within 72 h from the onset of surgery (perioperative) or not in that period (non-perioperative). Various demographic and characteristic variables of each case were collected and compared between groups. RESULTS Between 2001 and 2012, a total of 469 suspected TRALI cases were reported to Canadian Blood Services; 303 were determined to be within the TRALI diagnosis spectrum. Of those, 112 (38%) were identified as occurring during the perioperative period. Patients who underwent cardiac surgery requiring cardiopulmonary bypass (25.0%), general surgery (18.0%) and orthopedics patients (12.5%) represented the three largest surgical groups. Perioperative TRALI cases comprised more men (53.6% vs. 41.4%, p=0.04) than non-perioperative patients. Perioperative TRALI patients more often required supplemental O2 (14.3% vs. 3.1%, p=0.0003), mechanical ventilation (18.8% vs. 3.1%), or were in the ICU (14.3% vs. 3.7%, p=0.0043) prior to the onset of TRALI compared to non-perioperative TRALI patients. The surgical patients were transfused on average more components than non-perioperative patients (6.0 [SD=8.3] vs. 3.6 [5.2] products per patient, p=0.0002). Perioperative TRALI patients were transfused more plasma (152 vs. 105, p=0.013) and cryoprecipitate (51 vs. 23, p<0.01) than non-perioperative TRALI patients. There was no difference between donor antibody test results between the groups. CONCLUSION CBS data has provided insight into the nature of TRALI cases that occur perioperatively; this group represents a large proportion of TRALI cases.

Introduction of a closed-system cell processor for red blood cell washing: postimplementation monitoring of safety and efficacy

After introduction of a closed‐system cell processor, the effect of this product change on safety, efficacy, and utilization of washed red blood cells (RBCs) was assessed.

Peanut and fish allergy due to platelet transfusion in a child

An 8-year-old boy with no history of allergies received craniospinal radiation and cycles of autologous transplantations, which included chemotherapy and blood product support, for the treatment of medulloblastoma. A few weeks after his third cycle, he experienced anaphylaxis within 10 minutes after

ABO zygosity, but not secretor or Fc receptor status, is a significant risk factor for IVIG-Associated hemolysis

TO THE EDITOR: Although frequently effective[1][1],[2][2] and usually benign, high-dose (2 g/kg) intravenous immunoglobulin (IVIG) therapy can result in marked red blood cell (RBC) hemolysis, which in some cases is life threatening in severity.[3][3][⇓][4]-[5][5] The mechanism by which this

Specific IgEs passively transferred through a platelet transfusion caused two discrete allergic reactions to food

Case report A non-atopic 8 year old boy received multiple blood product transfusions as part of his treatment for meduloblastoma. He subsequently experienced anaphylaxis to salmon. Within minutes of eating salmon, he developed angioedema of the lip, facial erythema, throat discomfort and low blood pressure. Before this episode, he regularly ate fish with no reaction. The passive transfer of food specific IgE was suspected and he was advised to carry an epinephrine auto-injector and avoid all vertebrate fish. Specific IgE to salmon by ImmunoCAP was positive. Follow-up was arranged to follow his specific IgE to salmon with the expectation that his allergy would resolve. One week after his anaphylactic episode to fish, he developed an allergic reaction to peanuts. He ate a chocolate peanut butter cup and within 10 minutes he vomited, developed angioedema of the lip and experienced lethargy. Previously, he routinely ate peanuts without any symptoms. Skin prick testing showed positive results to peanut, salmon, mixed fish, and tree nut mix. He had a positive ImmunoCAP to peanut. Approximately 6 months later, he had undetectable ImmunoCAP results to both salmon and peanut. He resumed consumption of salmon and peanuts with no reaction. As part of the adverse event investigation by Canadian Blood Services all donors associated with the reaction were contacted and one donor stated that they have a severe allergy to peanuts, tree nuts, shellfish, and all fish including salmon. This information implicated one specific pooled platelet transfusion in which the platelets were suspended in the plasma of the atopic donor. The donor has been excluded from future donations. Conclusions