Geoff Lucas

Ten years of hemovigilance reports of transfusion‐related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma

BACKGROUND AND METHODS: From 1996 through 2006, 195 cases were reported as transfusion‐related acute lung injury (TRALI) to the Serious Hazards of Transfusion scheme and from 1999 onward classified by probability, using clinical features and HLA and/or HNA typing. From late 2003, the National Blood Service provided 80 to 90 percent of fresh‐frozen plasma (FFP) and plasma for platelet (PLT) pools from male donors.

The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion‐associated graft‐versus‐host disease

BACKGROUND: The pathogenesis of posttransfusion purpura (PTP) and transfusion‐associated graft‐versus‐host disease (TA‐GVHD) involves patient exposure to donor platelets (PLTs) and T lymphocytes, respectively, which are removed during blood component leukodepletion (LD).

Recommendations of the ISBT Working Party on Granulocyte Immunobiology for leucocyte antibody screening in the investigation and prevention of antibody-mediated transfusion-related acute lung injury.

Background  Transfusion‐related acute lung injury (TRALI) is currently one of the most common causes of transfusion‐related major morbidity and death. Among the many TRALI mediators, leucocyte antibodies have been identified as important triggers of severe TRALI.

A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene

X‐linked neutropenia (XLN, OMIM #300299) is a rare form of severe congenital neutropenia. It was originally described in a three‐generation family with five affected members that had an L270P mutation in the GTP‐ase binding domain (GBD) of the Wiskott‐Aldrich syndrome protein (WASP) [ Devriendt et al (2001) Nature Genetics, Vol. 27, 313–317 ]. Here, we report and describe a large three‐generation family with XLN, with 10 affected males and eight female carriers. A c.882T>C mutation was identified in the WAS gene, resulting in an I294T mutation. The infectious course is variable and mild in view of the profound neutropenia. In addition to the original description, low‐normal IgA levels, low to low‐normal platelet counts and reduced natural killer (NK)‐cell counts also appear as consistent XLN features. However, inverted CD4/CD8 ratios were not found in this family, nor were cases identified with myelodysplastic syndrome or acute myeloid leukaemia. Female carriers exhibited a variable attenuated phenotype. Like L270P WASP, I294T WASP is constitutively active towards actin polymerization. In conclusion, this largest XLN kindred identified to date provides new independent genetic evidence that mutations disrupting the auto‐inhibitory GBD of WASP are the cause of XLN. Reduced NK cells, low to low normal platelet counts and low to low‐normal IgA levels are also features of XLN.

Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines.

Background and Objectives  Transfusion‐related acute lung injury (TRALI) is associated with the passive transfusion of leucocyte antibodies in blood products. Blood Transfusion Services have adopted a number of different strategies for reducing the incidence of TRALI, but, while these have been successful, TRALI has not been completely eliminated. Many Transfusion Services have introduced leucocyte antibody screening of donors to further reduce TRALI. This report describes the results of donor leucocyte antibody screening within NHS Blood and Transplant and the guidelines that have been developed for Transfusion Services within the United Kingdom (UK) to reduce the incidence of TRALI.

Ninety-six suspected transfusion related acute lung injury cases: investigation findings and clinical outcome.

Abstract Transfusion related acute lung injury (TRALI) is one of the complications of blood transfusion and can result in major morbidity or mortality. The diagnosis depends upon the application of strict clinical criteria defining acute lung injury (ALI) and a temporal relationship to blood transfusion. We present the clinical and immunogenetic findings of 96 suspected TRALI cases investigated between 1996 and 2004. During this time period the national haemovigilance scheme (UK) defined TRALI as a reaction occurring either during or within 24 h of blood transfusion. Using clinical, laboratory and post mortem evidence, 64/96 cases could be defined as TRALI in our series. Sensitive techniques were employed to screen for HLA class I, class II and granulocyte specific antibodies in donor serum. Donor derived antibodies were detected in 58/64 (90%) of cases. Recipient derived DNA or cells were not always available but incompatibility was confirmed by the presence of the cognate antigen on recipient leucocytes or by crossmatching in 47/64 (73%) of cases. Cases referred prior to 2001 were not tested for HLA class II antibodies. By applying strict clinical criteria and using sensitive techniques a white blood cell antibody mediated immunological pathophysiology can be implicated in the majority TRALI cases.

Transfusion-related alloimmune neutropenia: an undescribed complication of blood transfusion

Alloimmune neutropenia in neonates is rare. We describe severe and persistent neutropenia in a 4-week-old neonate, which arose within 2 h of a transfusion of blood that contained about 28 mL of plasma and in which strong antibodies against human neutrophil antigen 1b (HNA-1b) were subsequently identified. The infant was positive for HNA-1b. No other likely cause of neutropenia was discovered. We believe this complication of blood transfusion to be a previously unrecognised one, and have called the condition transfusion-related alloimmune neutropenia (TRAIN).

Detection of platelet-reactive antibodies in patients who are refractory to platelet transfusions, and the selection of compatible donors

Although the frequency of alloimmunization against platelets, i.e. against human leucocyte antigens (HLA) class Iand platelet-specific human platelet alloantigens (HPA), has decreased as a result of leucocyte depletion of plateletand red-cell concentrates, refractoriness to platelet transfusions remains problematic [1]. There are still several points of interest concerning this, such as: the optimal technique(s) required to detect the alloantibodies; the actual association between the alloantibodies detected and refractoriness; the optimal policy for selecting compatible platelets for alloimmunized patients, and the impact of universal leucocyte depletion. To obtain information on these matters, the questions listed below were sent to experts in the field. Answers were obtained from 11. Question 1. Which techniques do you use to detect HLA class I antibodies in patients suspected of immunological refractoriness to platelet transfusions? Could you explain the reason for your choice of technique(s)? What is the frequency of cytotoxic and non-cytotoxic antibodies? Question 2. Which technique do you use to detect HPA antibodies? Could you explain your choice of technique(s)? What is the frequency of such antibodies in isolation and in combination with HLA class I antibodies? Question 3. What are your requirements for the cell panels used to detect HLA class I or HPA antibodies, e.g. number of cells, phenotypes required, etc? Question 4. Could you indicate the association you found between the antibodies detected and refractoriness? Question 5. Which policy do you apply to select compatible donors for refractory patients: (a) Selection of matched platelets? (b) Selection based on the specificity of the detected antibodies? (c) Cross-matching (please indicate techniques used)? Question 6. If you have implemented universal leucocyte depletion of cell concentrates, have you found a decrease in the frequency of alloimmunization?

Determination of human neutrophil antigen‐1, ‐3, ‐4 and ‐5 allele frequencies in English Caucasoid blood donors using a multiplex fluorescent DNA‐based assay

A number of DNA‐based methods to genotype the alleles coding for HNA have been described, but all require the separate amplification and analysis of each allele. The aim was to develop a DNA‐based method for simultaneous detection of HNA‐1, HNA‐3, HNA‐4 and HNA‐5 alleles.

Detection of HNA-3a and -3b antibodies using transfected cell lines and recombinant proteins.

BACKGROUND: HNA‐3 is a diallellic system located on choline transporter‐like protein 2 (CTL2), defined by a polymorphism at Amino Acid 154. HNA‐3a antibodies are of clinical importance in transfusion‐related acute lung injury but antibody detection requires labor‐intensive granulocyte isolation from HNA‐typed donors and the use of techniques such as the granulocyte agglutination test or granulocyte immunofluorescence test. Also, there is no commercial test for detection of HNA‐3 antibodies.