WBC Antibodies Research Articles

The pathophysiology and prevention of transfusion-related acute lung injury (TRALI): a review

Abstract Transfusion-related acute lung injury (TRALI) is a clinically important complication of transfusion that is often difficult to diagnose, is probably underreported, and likely has a multifactorial origin that is incompletely understood, making it challenging to find effective treatments and preventative steps. The spectrum of its severity and clinical symptoms seems wide, but its pathogenesis is most likely associated with pulmonary damage from activated recipient neutrophils. Despite the pathogenesis of TRALI being unclear, many severe cases are related to transfusion of donor WBC antibodies, and preventive measures based on avoiding donations by multiparous donors have been implemented at some sites, with early reports showing benefits. This review will address some of the questions surrounding the etiology of this potentially fatal reaction and how measures, predicated on many severe cases being related to transfusion of plasma from multiparous donors, led to preventive steps to avoid these donations. Immunohematology 2010;26:161–73.

Frequency and severity of transfusion-related acute lung injury – German haemovigilance data (2006–2007)

In an observational cohort study (2006-2007) the Paul-Ehrlich-Institut collected epidemiological data to investigate the frequency and causes of TRALI. Diagnosis of TRALI was confirmed according to criteria of the European Haemovigilance Network. Subsequent testing of white blood cell antibodies (WBC-Ab) against HLA or human neutrophil alloantigens was performed. Of a total of 187 reported TRALI cases, 44 could be confirmed consisting of 35 cases of antibody-mediated TRALI and nine cases of non-immune-mediated TRALI. Eight of 44 affected patients (18%) had a fatal outcome, seven cases with WBC-Ab positive plasma donors and one case with red blood cell donors. WBC antibodies were found in one male and 39 female donors. In 34 female donors, a history of pregnancy was confirmed. WBC-Ab positive donors presented four HLA class I antibodies, 15 HLA class II antibodies, 13 HLA class I and class II antibodies, one HNA-2a, and seven HNA-3a antibodies. WBC antibodies matching with recipient antigens were found exclusively in 28 female donors; 26 FFP donors, one platelet donor and one red blood cell donor. Reporting frequency of immune-mediated TRALI was 1:66,000 for fresh frozen plasma, 1:2.86 million for red blood cell concentrates and 1:420,000 for platelet concentrates. Reporting frequency of TRALI-related fatalities was 1:285,000 for FFP. Haemovigilance data show the significance of female donors with a history of pregnancy for the development of antibody-mediated TRALI. Manufacturing of FFP from male plasma and female donor screening for WBC-Ab could represent preventive measures.

P15 Transfusion Related Acute Lung Injury (TRALI) or Other Acute Lung Injury (ALI)?

Transfusion related acute lung injury (TRALI) is a form of acute lung injury (ALI) occurring within 6 h of transfusion. Patients presenting with TRALI are often indistinguishable from other causes of ALI. It is an increasingly recognized severe complication of transfusion. We present two cases where TRALI was strongly clinically suspected but only one case was serologically proven to be TRALI. Case 1: A 51 year old lady sustained a massive haemorrhage following an elective gynaecological procedure. 48 h later she returned to theatre and received 4 units of FFP and developed ALI. Case 2: A 28 year old had a postpartum haemorrhage following an emergency caesarian section. After receiving 3 units of RBC she developed respiratory failure. Both patients required ventilation but made a full recovery. Fluid overload, cardiogenic pulmonary oedema, sepsis and pulmonary thromboembolism were excluded and the cases were referred to the NBS for investigation of TRALI. In both cases, the expert panel consulted by the NBS was doubtful about the likelihood of TRALI since all 4 FFP units were collected from male donors and red cells are thought less likely to be implicated. However, all donors were contacted and investigated for WBC antibodies in their serum. Serology did not confirm the diagnosis in Case 1 but TRALI was confirmed in the second case where anti‐HNA1 antibodies were identified in one of the red cell donors and the patient typed as HNA‐1a positive. The diagnosis of TRALI is one of exclusion of other causes of ALI. Here we illustrate that despite the clinical similarities between the two patients, both strongly suspected of TRALI, only one was serologically confirmed to have TRALI. This highlights the difficulties in deciding which cases should be referred for further investigation. Although the referral process is complicated and requires a great deal of clinical input, TRALI needs to be considered as a cause of ALI following transfusion with all blood products, including RBCs. Finally, it is important to reach a diagnosis for both the patient concerned, as this may impact on their future management, and to exclude the implicated donors from further donations.

Alloimmunization in preterm infants after repeated transfusions of WBC-reduced RBCs from the same donor.

Preterm infants are among the most heavily transfused of patient groups, yet multiply transfused infants only rarely produce alloantibodies against RBC or WBC antigens. It is not known whether rates of alloimmunization might be increased by repeated exposure to RBCs and WBCs from the same donor, as in limited-donor-exposure programs, or whether infants might benefit from WBC-reduced RBC components as a means of diminishing the risk of possible alloimmunization. Preterm infants (birth weight 0.6-1.3 kg) received prestorage WBC-reduced RBCs from dedicated donors, collected in AS-3 as a means of limiting donor exposures. Blood samples were collected serially from infants shortly after birth until either discharge or age 6 months and were studied for RBC and WBC antibodies-the latter with reactivity against either HLA class I or neutrophil-specific antigens. Thirty preterm infants received 139 transfusions (mean, 4.6; median, 4 transfusions per infant), with 81 percent of transfusions obtained from one donor per infant. Eighty-four blood samples (mean, 2.7/infant) were studied, and no infant produced RBC antibodies. Twenty-seven percent of infants exhibited WBC antibodies, but only 13 percent actually produced WBC antibodies (passive maternal antibody excluded). Of the WBC antibodies produced by infants, three were against HLA class I and one was against neutrophil-specific antigens; none were linked to adverse effects. Because infants only rarely produce RBC antibodies, no changes in blood banking practices are necessary for limited-donor-exposure programs. Although the production of WBC antibodies by infants occurs, it seems to be uncommon; thus, the possible benefits, if any, of WBC reduction are uncertain, and further study is required before changes in practice can be justified.

Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions

Febrile nonhemolytic transfusion reactions (FNHTRs) are associated with white cell (WBC) antibodies. The purposes of this study were to determine the frequency of WBC antibodies, to associate the severity of reactions with antibody specificity, and to distinguish FNHTRs from infection and postoperative fever. By using the granulocyte indirect immunofluorescence test in conjunction with lymphocytotoxicity testing, it was found that 70 percent of FNHTRs in 24 patients involved WBC antibodies. The remaining 30 percent of apparent FNHTRs were associated with infections and postoperative fever. Granulocyte-specific antibodies were as prevalent as HLA antibodies and were associated with the severest reactions. Because FNHTRs occur with granulocyte-specific antibodies, HLA antibodies, and possible monocyte-specific antibodies (untested in this and other studies), these reactions could be grouped together as WBC-associated reactions.

Multiple transfusion fail to provoke antibodies against blood cell antigens in human infants.

We conducted studies of both red cell (RBC) and leukocyte (WBC) antibody formation in infants following multiple transfusions given during the first weeks of life. Fifty-three infants received 683 RBC transfusions from 503 different donors, plus 62 platelet, 4 granulocyte, and 53 fresh-frozen plasma units during the first 4 months of life. Three hundred fifty serum samples were obtained before, during, and after the transfusions. None of the infants formed unexpected RBC antibodies when tested at 37 degrees C by a two-cell low-ionic-strength solution antibody screen that included an anti-globulin phase. Twenty posttransfusion serums were negative when tested at room temperature. Lymphocytotoxic and granulocytotoxic WBC antibodies were measured in posttransfusion serums from 13 infants, and none were found. Despite exposure to many RBC and WBC antigens, no infants produced alloantibodies against blood cell antigens. Thus, immunologically mediated transfusion reactions should be quite rare in young infants, and this study supports recommendations of the American Association of Blood Banks Standards to omit repeat RBC compatibility testing during the first 4 months of life in infants whose initial RBC antibody screens reveal no unexpected antibodies.