ABO-immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non-identical transfusion.

BACKGROUND: Transfusion of ABO non-identical platelets has been associated with fatal haemolytic reactions, increased red cell transfusion needs and other adverse effects, but the practice of ABO matching in platelet transfusion is controversial. Immune complexes can be formed from the anti-A and/or anti-B antibodies and ABO soluble antigen(s) present in donor and recipient plasma after ABO non-identical transfusions. We hypothesized that these immune complexes affect recipient red cell structural integrity, platelet function and haemostasis. STUDY DESIGN AND METHODS: Haemolysis, platelet function and haemostatic function were assessed before and after incubation of recipient red cells, platelets and whole blood with normal saline controls, ABO-identical plasma controls or in vitro-generated ABO-immune complexes. RESULTS: ABO-immune complexes caused significantly increased haemolysis (P < 0·001), inhibition of platelet function (P = 0·001) and disruption of clot formation kinetics (P < 0·005) in both group A and O recipient samples. CONCLUSIONS: Substantial changes in platelet function, red cell integrity and haemostasis occur after in vitro exposure to immune complexes. These in vitro findings may explain, in part, previously observed associations of ABO non-identical platelet transfusions with adverse effects including increased red cell transfusion needs, organ failure and mortality.

What would Karl Landsteiner do? The ABO blood group and stem cell transplantation.

ABO blood group antigens, of great importance in transplantation and transfusion, are present on virtually all cells, as well as in soluble form in plasma and body fluids. Naturally occurring plasma IgM and IgG antibodies against these antigens are ubiquitous. Nonetheless, the ABO blood group system is widely ignored by many transfusion services, except for purposes of red cell transfusion. We implemented a policy of transfusing only ABO identical platelets and red cells in patients undergoing stem cell transplantation or treatment for hematologic malignancies. Major bleeding episodes have occurred in about 5% of patients undergoing induction therapy for acute leukemia as compared with 15-20% in the literature. Overall survival times appear to be superior to that in historical cohorts. In 2002-2004, treatment-related mortality at 100 days in our Blood and Marrow Transplant Unit was 0.7% for autologous transplants (n=148), 13% for sibling allogeneic transplants (n=110), and 24% (n=62) for matched unrelated allogeneic transplants, suggesting that our approach is safe. We speculate that more rigorous efforts on the part of transfusion services to provide ABO identical blood components, and to remove incompatible supernatant plasma, when necessary, might yield reduced morbidity and mortality in patients undergoing stem cell transplantation.

WBC-reduced blood transfusions and clinical outcome in children with acute lymphoid leukemia.

BACKGROUND: WBC reduction offers a variety of benefits to patients requiring multiple transfusions during induction therapy for childhood acute lymphoid leukemia (ALL), including reductions in febrile transfusion reactions, HLA alloimmunization, and CMV transmission. One potential benefit is a reduction in the deleterious effects of transfusion immunomodulation. In the surgical setting, transfusion immunomodulation has been linked to increases in postoperative infections and decreases in host cellular immunity that are mitigated by WBC reduction of transfused blood. STUDY DESIGN AND METHODS: A retrospective review was conducted of the medical records of 68 consecutive children undergoing induction therapy for newly diagnosed ALL from 1988 through 1995, a period whose midpoint is 1991, the year WBC reduction was introduced in this hospital. RESULTS: WBC reduction of platelet and RBC transfusions was associated with fewer days with fever (mean, 5.7 days [no WBC reduction] and 2.1 days [WBC reduction]; p = 0.012) and days with positive microbial cultures (mean, 1.5 [no WBC reduction] and 0.71 [WBC reduction]; p = 0.0055). There were more high-risk ALL patients in the group receiving WBC-reduced transfusions. CONCLUSION: Allogeneic WBCs in transfused blood may cause impairment of host defenses against microbial infection during induction therapy for childhood ALL.

Association of ABO-mismatched platelet transfusions with morbidity and mortality in cardiac surgery.

BACKGROUND: The transfusion of ABO-mismatched platelets has been associated with increased morbidity and mortality during induction therapy for acute leukemia and allogeneic progenitor cell transplantation. STUDY DESIGN AND METHODS: Reported here is a cohort study of 153 patients undergoing primary coronary artery bypass graft or coronary valve replacement surgery by two surgeons in one institution during 1997 and 1998. All statistics employed nonparametric two-sided tests (Mann-Whitney; Fisher's exact test). RESULTS: Patients receiving at least one ABO-mismatched pool of platelets had a significantly longer hospital stay, more days of fever, greater total hospital charges, and more RBC transfusions. Mortality, hours in the intensive care unit, days on antibiotics, and numbers of platelet transfusions were also greater in recipients of ABO-mismatched platelets, but these differences were of less statistical significance. When the analysis was restricted to the 139 patients who received no more than two pools of platelets, the trends for increased morbidity and mortality (8.6% vs. 1.9%; p = 0.10) in recipients of ABO-mismatched platelets persisted. The number of RBC transfusions required in this latter cohort was 50 percent greater (mean, 6.1 vs. 9.2; p = 0.02), despite the fact that the number of platelet transfusions given was similar (mean, 1.2 vs. 1.3 pools; p = 0.22). CONCLUSIONS: ABO-mismatched platelet transfusions are associated with unfavorable outcomes in cardiac surgery, a relationship that remains unexplained. As this association has been found in three cohort studies in various clinical settings, further investigation of this association is warranted.

Platelet washing to prevent recurrent febrile reactions to leucocyte-reduced transfusions.

Symptoms of fever and/or rigours after transfusion continue to occur commonly in patients receiving platelets leucocyte-reduced after storage. A cohort of 24 consecutive patients who had experienced severe or repeated febrile nonhaemolytic reactions to post-storage leucocyte-reduced platelet transfusions were treated with saline-washed, post-storage leucocyte-reduced platelets. The frequency of reactions declined from 20% of transfusions (n = 191) to 0.6% (n = 331) after instituting saline-washed, post-storage leucocyte-reduced platelet transfusions. These results support the hypothesis that substances present in the supernatant of stored platelet concentrates mediate febrile nonhaemolytic transfusion reactions, and provide one strategy for preventing their occurrence.

Mortality risks, costs, and decision making in transfusion medicine.

Traditional quality-adjusted life year (QALY) cost analysis is complex and assigns arbitrary dollar values to catastrophic outcomes such as death. Analysis of transfusion medicine technologies by an alternative approach that focuses on costs to avoid fatal outcomes might be a useful adjunct to QALY analysis for allocating limited financial resources. We estimated the cost per death averted for the following interventions: apheresis platelets vs random platelets, solvent detergent-treated plasma vs untreated plasma, and leukocyte-reduced vs unmodified transfusions in cardiac surgery. As a control, similar data were calculated for current donor viral testing. The estimated incremental costs per death avoided were as follows: single-donor apheresis platelets, $15 million; solvent detergent plasma, $17 million; leukocyte-reduced transfusions in cardiac surgery, $11,000; HIV-1 antibody testing, $22,000; and HIV-1 antigen testing, $3.9 million. The estimated number of deaths averted per year in our hospital were as follows: apheresis platelets, 0.1; solvent detergent plasma, 0.044; leukocyte-reduced transfusions, 14; HIV-1 antibody testing, 6.0; and HIV-1 antigen testing, 0.033. HIV-1 antibody testing and leukocyte-reduced transfusions in cardiac surgery are comparably cost-efficient means of averting mortality in patients receiving transfusions. Solvent detergent plasma and apheresis platelets are comparatively expensive approaches to reducing mortality from transfusion complications.

A cost analysis of autologous and allogeneic transfusions in hip-replacement surgery.

PURPOSE: To analyze the cost consequences of autologous versus allogeneic transfusions. METHODS: Costs were determined when allogeneic transfusions were given in addition to, or instead of, autologous transfusions. Hospital charges were used to estimate costs for hip-replacement surgery. The main outcome measure was estimated incremental hospital costs per unit transfused. RESULTS: Among donors of autologous blood, mean total charges were $7,200 greater for recipients of both autologous and allogeneic transfusions than for recipients of autologous transfusion only (P=0.0001). Each allogeneic transfusion was associated with additional costs of $1,480. In a second cohort of patients receiving identical amounts of either allogeneic or autologous blood (mean=2.3 units), total hospital charges were a mean of $4,800 greater (P=0.0001) for allogeneic recipients. The per unit excess costs associated with each unit of allogeneic blood cohort were $1,043. CONCLUSIONS: Allogeneic transfusions are associated with incremental hospital costs of about $1,000 to $1,500 per unit transfused when compared with costs for similar patients receiving no transfusions or 1 to 5 units of autologous blood.

Current research on the immunomodulatory effect of allogeneic blood transfusion.

This review summarizes three aspects of current research on the immunomodulatory effect of allogeneic transfusion. Representatives of three laboratories-each of which is actively engaged in research on transfusion-induced immunomodulation-summarize their current investigative approach. First, current animal models of transfusion-induced immunomodulation are presented and research on the tumor growth-promoting effect of allogeneic transfusion is described. Second, mechanisms underlying an immunomodulatory effect of transfusion are summarized and experiments on the induction of transplant tolerance by selective introduction of donor-type MHC antigens is presented. Third, the potential clinical impact of increased infection and tumor recurrence resulting from transfusion-induced immunomodulation is assessed. The potential role of donor-derived hematopoietic stem cells is presented as an area of future investigation in the area of transfusion-induced immunomodulation.

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 Fc gamma RII (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 Fc gamma RII 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.