Frequency of heparin/platelet factor 4-dependent platelet antibodies in patients undergoing angioplasty and stenting for cardiovascular disease and their role for on-clopidogrel platelet reactivity.

BACKGROUND: The frequency of heparin-induced platelet antibodies (H/PF4 antibodies) following heparin exposure during percutaneous intervention with stent implantation is unknown. These antibodies may activate platelets and therefore contribute to high on-clopidogrel residual platelet reactivity (HRPR). METHODS: We screened 288 patients after angioplasty and stenting for H/PF4 antibodies by an IgG/A/M ELISA. The 44 (15.3%) positive samples were further evaluated for IgG only antibodies, by the particle gel immunoassay (PaGIA), the heparin induced platelet activation assay (HIPA) and MEA. Further, we determined on-treatment platelet reactivity by multiple electrode aggregometry (MEA) in these patients. In vivo platelet activation was assessed by P-selectin expression. RESULTS: The prevalence of H/PF4 antibodies in the total patients' cohort was 15.3% (95% CI 11.3-20%) by the IgG/A/M ELISA, 9.4% (95% CI 6.3-13.4%) by the IgG ELISA, 11.5% (95% CI 8-15.7%) by PaGIA, 14.2% (95% CI 10.4-18.8%) by MEA, and 2.4% (95% CI 1-4.9%) by HIPA. On-treatment platelet reactivity was similar between patients without and with H/PF4 antibodies [39 AU (6-110 AU) vs. 41 AU (7-91 AU); P = 0.85]. HRPR was seen in 105 patients (37.5%), and occurred to a similar extent in patients without and with H/PF4 antibodies in all test systems (all P > 0.2). Further, there was no difference of the ELISA optical densities using the IgG/A/M or the IgG only ELISA between patients without or with HRPR (all P > 0.3). There was no significant difference of P-selectin expression between patients without or with H/PF4 antibodies (P = 0.97). Noteworthy, none of the patients who developed H/PF4 antibodies had heparin-induced thrombocytopenia or a thromboembolic event. CONCLUSION: H/PF4 antibodies are not rare in patients undergoing angioplasty and stenting. However, these antibodies are not associated with the occurrence of HRPR.

Performance characteristics of two commercially available IgG-specific immunoassays in the assessment of heparin-induced thrombocytopenia (HIT).

BACKGROUND: The in vitro demonstration of antibodies against platelet factor-4/heparin (PF4/hep) complexes is an important contribution to the diagnosis of heparin-induced thrombocytopenia (HIT). The use of PF4/hep IgG-specific immunoassays enhances the specificity of HIT-investigations without any impairment of the sensitivity. Several IgG-specific immunoassays with different origin and structure of the target antigen-complex are commercially available. METHODS: Using a retrospective cohort consisting of 459 patients suspected to have HIT, we compared the performance characteristics of two commercially available IgG-specific immunoassays, GTI- (Genetic Testing Institute) and HIA-IgG-ELISA (Hyphen Biomed Research). RESULTS: PF4/hep antibodies were detected in 85 and 81 sera using GTI- and HIA-IgG-ELISA, respectively. OD values and clinical likelihood of patients who tested positive in one assay only were significantly lower than in those who tested positive in both immunoassays. Both IgG-specific assays showed high negative predictive values (100%) and similar but unsatisfactory positive predictive values, determined by a minimum clinical score of 5 and a positive HIPA result (41% and 43%, respectively). The implementation of a confirmatory step using excessive heparin increased the PPV of both assays, but results in a reduction of NPV in HIA-IgG-ELISA. CONCLUSIONS: The detection of IgG antibodies alone improves the clinical usefulness of immunoassays. However, functional assays remain indispensable to avoid the overdiagnosis of HIT caused by the detection of IgG non-platelet activating antibodies. The OD value in IgG immunoassays appears to correlate with the clinical relevance of the antibodies and might be used as a predictive parameter in the assessment of HIT.

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II-induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody-dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody-induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures.

Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

A novel enzyme-linked immunosorbent assay method for the detection of human neutrophil antigen-2a antibodies.

BACKGROUND: Antibodies to human neutrophil antigen (HNA)-2a are responsible for a number of immune-mediated neutropenia disorders. Although several methods exist for the identification of anti-HNA-2a, all these methods have several limitations. In this study, a solid-phase enzyme-linked immunosorbent assay (ELISA) using recombinant HNA-2a antigen (rHNA-2a) allowing rapid detection of HNA-2a antibodies was developed. STUDY DESIGN AND METHODS: Soluble rHNA-2 was generated by transfection of insect cells with CD177 vector. Purified rHNA-2a was immobilized on microtiter wells coated with anti-CD177 and was applied to analyze 10 sera containing HNA-2a antibodies. For the evaluation of the ELISA method, results were compared with the standard assay, MAIGA (monoclonal antibody antigen capture assay) for detection of neutrophil antibodies. RESULTS: The specificity of HNA-2a antibodies in all sera was confirmed by immunoblotting. Sera were then tested simultaneously in ELISA and MAIGA assays. Nine of 10 sera showed positive reactions in ELISA, whereas only 9 of 10 sera reacted in the standard MAIGA assay. All HNA-2a antibodies were detectable in MAIGA when diluted sera were applied. No reaction was observed with different sera containing neutrophil-reactive antibodies (6 anti-HNA-1a, 4 anti-HNA-1b, and 20 anti-HLA Class I and II) in ELISA. All HNA-2a antibodies were detectable in MAIGA when diluted sera were applied. Notably, sera containing anti-proteinase 3 (PR3) from patients with Wegener's granulomatosis reacted in MAIGA. In contrast, this antibody showed no reaction in ELISA with purified rHNA-2a. CONCLUSIONS: These results demonstrated that ELISA with rHNA-2a provides a good method for detecting HNA-2a antibodies in human serum. This assay enables to exclude the presence of autoantibody against PR3 in patient's sera, which cannot be differentiated from anti HNA-2a with current serologic methods.

Blockade of maternal anti-HPA-1a-mediated platelet clearance by an HPA-1a epitope-specific F(ab') in an in vivo mouse model of alloimmune thrombocytopenia.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is most commonly caused by transplacental passage of maternal human platelet-specific alloantigen (HPA)-1a antibodies that bind to fetal platelets (PLTs) and mediate their clearance. SZ21, a monoclonal antibody (MoAb) directed against PLT glycoprotein IIIa, competitively inhibits the binding of anti-HPA-1a alloantibodies to PLTs in vitro. The purpose of this investigation was to determine whether SZ21 F(ab')(2) fragments might be therapeutically effective in inhibiting or displacing maternal HPA-1a antibodies from the fetal PLT surface and preventing their clearance from circulation. STUDY DESIGN AND METHODS: Resting human PLTs from HPA-1ab heterozygous donors were injected into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Purified F(ab')(2) fragments of SZ21 or control immunoglobulin G (IgG) were injected intraperitoneally 30 minutes before introduction of HPA-1a antibodies. Blood samples were taken periodically and analyzed by flow cytometry to determine the percentage of circulating human PLTs. RESULTS: Anti-HPA-1a IgG from NAIT cases were able to efficiently clear HPA-1a-positive PLTs from murine circulation. Administration of SZ21 F(ab')(2) fragments not only inhibited binding of HPA-1a antibodies to circulating human PLTs, preventing their clearance, but also displaced bound HPA-1a antibodies from the PLT surface. CONCLUSION: F(ab')(2) fragments of HPA-1a-selective MoAb SZ21 effectively inhibit anti-HPA-1a-mediated clearance of human PLT circulating in an in vivo NOD/SCID mouse model. These results suggest that agents that inhibit binding of anti-HPA-1a to PLTs may have therapeutic potential in the treatment of NAIT.

Transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare complication of blood transfusion that has a fatal outcome in most patients. It is caused by the transfusion of viable T cells present in blood products that are not rejected by the transfusion recipient, either because of recipient immunodeficiency or because of a common HLA haplotype between the blood donor and recipient. Because effective treatment is not available, risk identification and prevention are of central importance. Among the potential risk factors that have been discussed to date, a definite hazard for developing TA-GvHD has been recognized for HLA-matched transfusions or transfusions from blood relatives, intrauterine and exchange transfusions, patients with congenital immunodeficiency syndromes, bone marrow transplantation, stem cell transplantation, or lymphomas. Patients at possible TA-GvHD risk who will require further evaluation include patients with hematologic malignancies, solid tumors, or solid organ transplantation. Although postulated, an increased risk for term or preterm newborns and patients with HIV/AIDS has not thus far been demonstrated.

Pulmonary transfusion reactions.

BACKGROUND: In recent years, pulmonary transfusion reactions have gained increasing importance as serious adverse transfusion events. METHODS: Review of the literature. RESULTS: Pulmonary transfusion reactions are not extremely rare and, according to hemovigilance data, important causes of transfusion-induced major morbidity and death. They can be classified as primary with predominant pulmonary injury and secondary as part of another transfusion reaction. Primary reactions include transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO) and transfusion-associated dyspnea (TAD). Secondary pulmonary reactions are often observed in the wake of hemolytic transfusion reactions, hypotensive/anaphylactic reactions, and transfusion-transmitted bacterial infections. CONCLUSION: Knowledge and careful management of cases of pulmonary transfusion reactions are essential for correct reporting to blood services and hemovigilance systems. Careful differentiation between TRALI and TACO is important for taking adequate preventive measures.

[Transfusion-related acute lung injury (TRALI)]. / Transfusionsassoziierte akute Lungeninsuffizienz (TRALI)--Diagnose, Therapie und Prävention.

According to data of international hemovigilance registries, transfusion-related acute lung injury (TRALI) has emerged as the leading cause of transfusion-related mortality. Errors in the transfusion process, leading to ABO incompatible transfusion, represent the second most frequent cause of transfusion-related mortality, while infection risks of transfusion declined significantly. The following article describes the clinical picture of TRALI, its pathogenesis, diagnostic criteria as well as therapy recommendations and discusses possible preventing measures.

The pathogenesis of transfusion-related acute lung injury and how to avoid this serious adverse reaction of transfusion.

Transfusion-related acute lung injury (TRALI) is a serious, life-threatening complication of blood transfusion. Available evidence strongly suggests that leukocyte antibodies present in donor plasma are the predominant mechanism in TRALI. These antibodies lead to recipient neutrophil activation, with activated neutrophils inducing endothelial and alveolar damage in the lungs. These mechanisms are discussed in detail as are the alternative mechanisms that have been proposed. Preventive strategies that may help to reduce TRALI are presented.

Rapid detection of HPA-1 alloantibodies by platelet antigens immobilized onto microbeads.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is one of the most common bleeding disorders in neonates. It occurs when alloantibodies from an immunized mother react with paternally inherited alloantigens, mostly human platelet antigen 1a (HPA-1a), on the fetal platelets (PLTs). Currently, monoclonal antibody-immobilized PLT antigen (MAIPA) assay represents the standard technique for the serologic diagnosis of NAIT. MAIPA is time-consuming, however, and limited by the availability of monoclonal antibodies (MoAbs). Here, a gel antigen-specific assay (GASA) was developed, which allows rapid detection of HPA-1 alloantibodies without the use of MoAbs. STUDY DESIGN AND METHODS: Glycoprotein (GP) IIb/IIIa was purified by affinity chromatography from outdated PLT concentrates derived from HPA-1aa or HPA-1bb donors. Purified GPs were biotinylated, immobilized onto streptavidin beads, and used for the analysis of HPA-1a alloantibodies by a microtyping system. HPA-1a serum samples derived from mothers with NAIT (n = 36) and from posttransfusion purpura patients (n = 2) as well as HPA-1b (n = 4), HPA-5b (n = 2), HPA-3a (n = 4), and HLA Class I (n = 2) alloantiserum samples from multitransfused patients were investigated in GASA and MAIPA assays. RESULTS: GASA was able to detect all HPA-1a and -1b alloantibodies recognized by MAIPA. Cross-reactivity with other PLT-reactive alloantibodies was not observed. Interestingly, 3 of 36 serum samples, which showed only moderate reactivity in MAIPA, reacted strongly in GASA. CONCLUSION: GASA has proved to be a rapid method for the detection of HPA-1a alloantibodies and maybe useful for PLT antibody screening, especially in initial assessment of suspected NAIT cases.

The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31).

Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colony-stimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time protein-protein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration.

In vivo thrombus formation in murine models.

Platelets play a central role in hemostasis, but also in atherothrombosis, as they rapidly adhere to tissue and to one another as a response to any vascular injury. This process involves a large number of surface receptors, signaling pathways, and enzymatic cascades as well as their complex interplay. Although in vitro experiments proved successful in both identifying new receptors and pathways and developing potent and selective antithrombotic drugs, in vitro research cannot mimic the myriad hemodynamic and spatiotemporal cellular and molecular interactions that occur during the generation and propagation of thrombi in vivo. Animal models, and, with the availability of genetically modified mouse strains and of modern intravital imaging techniques, mouse models in particular, have opened new ways to identify both individual roles and the interplay of platelet proteins in complex in vivo settings. In vivo models revealed the important role of, eg, Gas6 or blood coagulation factor XII in thrombus formation, and results obtained in in vivo models raised the interesting possibility that (physiologic) hemostasis and (pathologic) thrombosis might represent 2 mechanistically different processes. This review summarizes in vivo findings that contributed significantly to our understanding of hemostatic and thrombotic processes and which may help to guide future research.

The pathogenesis of transfusion-related acute lung injury (TRALI).

In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

Safety and efficacy of therapeutic early onset granulocyte transfusions in pediatric patients with neutropenia and severe infections.

BACKGROUND: Bacterial and fungal infections in profound neutropenia after chemotherapy are associated with high mortality despite appropriate antibacterial and antifungal treatment. Granulocyte transfusions are used as a therapeutic addendum, but concern regarding pulmonary reactions often results in delayed use in clinical practice. Accordingly, many patients are already at advanced stages of their infectious disease once granulocytes are transfused. Thus, a prospective Phase II trial was conducted to test the safety and efficacy of therapeutic early-onset granulocyte transfusions in immunocompromised children with neutropenia and severe infections. STUDY DESIGN AND METHODS: Twenty-seven children with hematologic disorder or malignancy and severe neutropenia with clinically and/or microbiologically documented severe infection unresponsive to standard treatment were included. They received granulocyte colony-stimulating factor (G-CSF)-elicited, crossmatched granulocyte concentrates every other day until complete recovery from infection was documented. RESULTS: A median of two granulocyte transfusions with a median of 8 x 10(8) granulocytes per kilogram of body weight were administered. All transfusions were well tolerated, and no pulmonary symptoms were observed. A total of 92.6 percent of our patients were able to clear their initial infection, and 81.5 percent were alive and without signs or symptoms of their infection 1 month later. All six children with aspergillosis cleared their infection. CONCLUSIONS: G-CSF-elicited, crossmatched granulocyte concentrates are a safe and efficient therapeutic addendum in immunocompromised children with prolonged neutropenia and severe infections. Early transfusion of granulocyte concentrates can lead to an overall response rate of 92.6 percent without adverse events. Randomized clinical trials with an early-onset design are required to determine appropriate clinical applications.

A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor alpha-chain promoter.

The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn-dependent transport across the placenta may influence antibody-mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1-VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7.5 and 92.0%, respectively). Real-time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1.66-fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0.002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0.003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0.021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG-binding capacities.

Reduced thrombus stability in mice lacking the alpha2A-adrenergic receptor.

Platelet activation plays a central role in hemostasis and thrombosis. Many platelet agonists function through G-protein-coupled receptors. Epinephrine activates the alpha(2A)-adrenergic receptor (alpha(2A)) that couples to G(z) in platelets. Although alpha(2A) was originally cloned from platelets, its role in thrombosis and hemostasis is still unclear. Through analysis of alpha(2A)-deficient mice, variable tail bleeding times were observed. In vitro, epinephrine potentiated activation/aggregation responses of wild-type but not alpha(2A)-deficient platelets as determined by flow cytometry and aggregometry, whereas perfusion studies showed no differences in platelet adhesion and thrombus formation on collagen. To test the in vivo relevance of alpha(2A) deficiency, mice were subjected to 3 different thrombosis models. As expected, alpha(2A)-deficient mice were largely protected from lethal pulmonary thromboembolism induced by the infusion of collagen/epinephrine. In a model of FeCl(3)-induced injury in mesenteric arterioles, alpha(2A)(-/-) mice displayed a 2-fold increase in embolus formation, suggesting thrombus instability. In a third model, the aorta was mechanically injured, and blood flow was measured with an ultrasonic flow probe. In wild-type mice, all vessels occluded irreversibly, whereas in 24% of alpha(2A)-deficient mice, the initially formed thrombi embolized and blood flow was reestablished. These results demonstrate that alpha(2A) plays a significant role in thrombus stabilization.

Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model.

Transfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.

White blood cell-reactive antibodies are undetectable in solvent/detergent plasma.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Although all types of blood products have been associated with TRALI, fresh-frozen plasma (FFP) is the most commonly implicated component. It has been postulated that TRALI is an immune-mediated event, because white blood cell (WBC)-reactive antibodies in the donor's plasma are frequently associated with the syndrome. In contrast to single donor-derived FFP, solvent/detergent (S/D) plasma is produced from multiple donations, leading to an at least 500-fold dilution of a single plasma unit. It was hypothesized that WBC-reactive antibodies are undetectable in S/D FFP. STUDY DESIGN AND METHODS: Twenty batches of S/D FFP (5 of each ABH group) were analyzed with well-established routine techniques to detect WBC antibodies. RESULTS: All samples tested negative for granulocyte-specific as well as HLA Class I and Class II antibodies. CONCLUSIONS: Different strategies to reduce the risk of TRALI are currently discussed. These include screening of all potentially immunized donors for WBC-reactive antibodies and exclusion of multiparous or all women from donating FFP. Here, it is demonstrated that neither granulocyte- nor lymphocyte-reactive antibodies are detectable in S/D FFP. Thus, S/D FFP may represent a potential alternative to reduce the risk of TRALI associated with the transfusion of FFP.