Robertson D. Davenport

Toward an understanding of transfusion‐related acute lung injury: statement of a consensus panel

From Kleinman Biomedical Research, Victoria, British Columbia, Canada; the University of British Columbia, Vancouver, British Columbia, Canada; the University of Alberta, Edmonton, Alberta, Canada; Toronto, Ontario, Canada; the University of Michigan, Ann Arbor, Michigan; The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin; Elora, Ontario; Canada; McMaster University, Hamilton, Ontario, Canada; the Royal Columbian Hospital, New Westminster, British Columbia, Canada; Halifax, Nova Scotia, Canada; the Quebec Public Health Institute, Montreal, Quebec, Canada; McGill University, Montreal, Quebec, Canada; and the University of Toronto, Toronto, Ontario, Canada. Address reprint requests to: Morris Blajchman, MD, Depts. of Pathology and Medicine, McMaster University, 1200 Main St., West, HSC 2N34, Hamilton, Ontario, Canada L8N 3ZS; e-mail: blajchma@mcmaster.ca. Dr Meade is a Peter Lougheed Scholar of the Canadian Institutes of Health Research. This Consensus Conference was funded by Canadian Blood Services and Hema-Quebec, with additional support from the International Society of Blood Transfusion’s Biomedical Excellence for Safer Transfusion (BEST) subcommittee. Received for publication August 22, 2004; revision received August 26, 2004, and accepted August 26, 2004. TRANSFUSION 2004;44:1774-1789. R E V I E W

Evidence-based practice guidelines for plasma transfusion

BACKGROUND: There is little systematically derived evidence‐based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma.

Molecular Genetic Analysis of the ABO Blood Group System: 1. Weak Subgroups: A3 and B3 Alleles

We have determined the nucleotide sequences of the coding region in the last two coding exom of ABO genes (which occupy 91% of the soluble form of A1 transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A3 phenotype and 3 individuals had a B3 phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A3 allele and 1 case of the B3 allele were found to contain a single‐base substitution which resulted in an amino acid substitution. However, no other cases of A3 and B3 alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level.

Nanoliter viscometer for analyzing blood plasma and other liquid samples

We have developed a microfabricated nanoliter capillary viscometer that quickly, easily, and inexpensively measures the viscosity of liquids. The measurement of viscosity is based on capillary pressure-driven flow inside microfluidic channels (depth approximately 30 microm and width approximately 300 microm). Accurate and precise viscosity measurements can be made in less than 100 s while using only 600 nL of liquid sample. The silicon-glass hybrid device (18 mm by 15 mm) contains on-chip components that measure the driving capillary pressure difference and the relevant geometrical parameters; these components make the nanoliter viscometer completely self-calibrating, robust, and easy to use. Several different microfabricated viscometers were tested using solutions with viscosities ranging from 1 to 5 cP, a range relevant to biological fluids (urine, blood, blood plasma, etc.). Blood plasma samples collected from patients with the symptoms of hyperviscosity syndrome were tested on the nanoliter capillary viscometer to an accuracy of 3%. Such self-calibrating nanoliter viscometers may have widespread applications in chemical, biological, and medical laboratories as well as in personal health care.

Transfusion-related acute lung injury: femme fatale?

312 TRANSFUSION Volume 41, March 2001 www.transfusion.org Virtually every type of blood component has been associated with TRALI, with the significant exception of plasma derivatives.3 In most instances, the implicated component contains more than 60 mL of plasma, but it is apparent that smaller quantities can initiate the pulmonary event. The precise mechanism of TRALI in unknown, but there are a number of clues that it is an immune-mediated event. Unlike those in most immunologically triggered transfusion reactions, the pathologic antibodies in TRALI typically are of donor, rather than recipient, origin. Numerous reports have documented the presence of HLA-specific or granulocyte antibodies in the plasma of the donors of implicated blood components. Popovsky and Moore1 found such antibodies in 89 percent of 36 cases. In about one-half of the cases they studied, the HLA-A or -B antibodies of the implicated donor corresponded with one or more of the HLA epitopes of the recipient. In other reports,5,6 neutrophil-specific antibodies (anti-NA2, -5b, -NB1, -NB2) have been identified in implicated units. In another large series,7 granulocyte antibodies were identified more frequently (41%) than HLA antibodies (28%). HLA antibodies have frequently been found in multiparous female donors. An early study8 found leukoagglutinins in 18 percent of parous women, more than half of whom had detectable antibodies 3 years or more after their last pregnancy. A recent study of plateletpheresis donors9 found HLA antibodies in 26 percent of women with three or more previous pregnancies. Of particular concern are several reports of TRALI resulting from mother-to-child directed donations.10,11 This setting may be particularly likely to cause TRALI, as the mother may have developed antibodies to the child’s WBC antigens during pregnancy. A few cases of TRALI have been reported in which the recipient had antibodies directed against donor WBC antigens. It is unclear why these antibodies may have resulted in lung injury, rather than the more common febrile reactions and platelet refractoriness. Despite the established association of transfused WBC antibodies with TRALI, no antibody has been identified in either the patient or donor in up to 15 percent of cases. Recent reports describing HLA class II antibodies, rather than class I, in donor serum in TRALI cases suggest that a broader ranger of specificities may be involved.12 Silliman and colleagues13 advanced an alternative hypothesis. They Transfusion-related acute lung injury: femme fatale?

Anti-A and anti-B titers in pooled group O platelets are comparable to apheresis platelets.

BACKGROUND: Although uncommon, acute hemolytic transfusion reactions (AHTRs) have been reported after transfusion of group O single‐donor apheresis platelets (SDPs) to group A, B, and AB recipients. Current methods for identifying “high‐titer” SDPs include tube and gel methods. The risk of a high‐titer unit is considered low with group O, poststorage, pooled platelet concentrates (PPLTs); however, data regarding anti‐A and anti‐B titers in PPLTs are lacking.

A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma

BACKGROUND: The COBE Spectra AutoPBSC collection set (AUTO‐kit; CaridianBCT) is a popular dual‐stage collection set for peripheral blood progenitor (PBPC) collection. Although the AUTO‐kit is purportedly equivalent to the white blood cell (WBC) collection set (WBC‐kit) for PBPC collection, improved CD34 yields after switching from the AUTO‐kit to the WBC‐kit were anecdotally observed, particularly in patients with higher WBC counts. A prospective, randomized trial of the AUTO‐ and WBC‐kits for PBPC collection in multiple myeloma (MM) patients was therefore designed.

Cytophotometric measurements of hürthle cell tumors of the thyroid gland. Correlation with pathologic features and clinical behavior

The DNA content and nuclear size and shape of 21 Hürthle cell neoplasms of the thyroid were analyzed with a CAS 100RS Image Analyzer (Cell Analysis Systems, Lombard, IL) in order to distinguish between benign and malignant lesions. Neoplasms were considered malignant if documented metastatic disease or pathologic evidence of vascular or capsular invasion was present. Of the ten neoplasms classified as malignant, eight were aneuploid and two were diploid. Nine of the 11 benign neoplasms were diploid, the remaining two neoplasms were aneuploid. Two of the four malignant neoplasms which recurred or metastasized were aneuploid, the other two were diploid. A statistically significant association was found between aneuploidy and tumor invasion (P = 0.007). However, measurement of the percentage of cycling tumor cells as well as nuclear size and shape were not useful in separating benign from malignant neoplasms.

Non‐Hodgkin's lymphoma of the brain after Hodgkin's disease. An immunohistochemical study

Non‐Hodgkins lymphoma (NHL) of the central nervous system (CNS) is a rarely reported complication of Hodgkins disease (HD). Two patients with NHL of the brain after HD were studied by histologic and immunohistochemical methods. Both patients were in the second decade, had been treated with radiation and chemotherapy, had experienced a relapse of HD before development of NHL, had no evidence of HD at the time of diagnosis of NHL, and died within 1 year of diagnosis. Both brain neoplasms were large cell immunoblastic lymphomas of B‐cell lineage. Patients with HD appear to be at increased risk for NHL of the CNS, which may have a poor prognosis.

Safety of leukoreduced, cytomegalovirus (CMV)-untested components in CMV-negative allogeneic human progenitor cell transplant recipients

Transfusion-transmitted cytomegalovirus (TT-CMV) infection can lead to significant morbidity and mortality in CMV-negative (CMV-N) hematopoietic progenitor cell (HPC) transplant patients. In 1995, Bowden and colleagues demonstrated the efficacy of leukoreduced components to reduce TT-CMV in most high-risk populations, although there remained safety concerns in CMV-N allogeneic HPC transplant recipients. As a result, several transplant programs recommended both leukoreduced and CMV-N components for CMV-N allogeneic HPC patients receiving transplants from CMV-N donors (CMV). A more recent study, however, has challenged the clinical benefit of requiring CMV-N, in addition to leukoreduction, in CMV HPC patients. In a 10-year study, Thiele and colleagues found no cases of TT-CMV in 23 CMV HPC patients transfused with 1847 CMVuntested (CMV-U), leukoreduced components. We would like to share our institution’s experience in 100 CMV allogeneic HPC patients transfused with 6465 CMV-N and CMV-U cellular components. Before July 2006, the University of Michigan provided, when available, CMV-N components to all CMV HPC transplant recipients. A preliminary 12-month retrospective review showed that 52% (14/27, 2004) had received leukoreduced, CMV-U blood components due to shortages in CMV-N products, with no cases of TT-CMV. As a result, the transfusion policy was changed in mid-2006 to provide leukoreduced, CMV-U products for all HPC patients, regardless of pretransplant CMV status. For quality assurance, we monitored the CMV conversion rate over a 36-month period (January 2005 to December 2007) covering an 18-month period before and after the change in transfusion policy (Table 1). Per institutional practice, CMV-N patients were screened for CMV IgG every 1 to 2 months pretransplant, followed by regular testing for CMV nucleic acid testing (NAT) after transplant. The minimum posttransplant follow-up was 12 months. All blood products were provided by Southeast Michigan American Red Cross (Detroit, MI) and were leukoreduced after storage (Leukotrap RC system, Pall Corp., Port Washington, CA). As shown in Table 1, 100 patients were available for analysis and included both adult and pediatric patients. All patients were CMV-N before transplant, received a CMV allogeneic HPC transplant, and underwent weekly posttransplant CMV NAT monitoring. Except for sex, there were no significant differences in patient demographics, transplant type, or transfusion support in the two study cohorts. In the CMV-N policy period, only 11% to 15% of cellular components were CMV-N, with most patients receiving a mix of CMV-N and CMV-U. Only five patients received 100% CMV-N products. All five patients had low transfusion needs, requiring 2 to 10 red blood cell (RBC) and two to three platelet (PLT) transfusions. Two adult male patients had a single positive test for CMV IgG at 3 and 5 weeks after transplant, respectively (Table 1). Both patients tested negative for CMV IgM and CMV NAT and had no evidence of clinical CMV infection. Each patient received between 42 and 45 CMV-U cellular components in the weeks before seroconversion: neither patient had received intravenous immune globulin before CMV IgG testing. There were no CMV seroconversions in the CMV-U period. The overall CMV IgG seroconversion rate was 2% per patient and 0.03% per unit, which is comparable to the findings by Bowden and coworkers (2.4% per patient, 0.023% per component). The rate of confirmed TT-CMV was 0%, consistent with the study by Thiele and coworkers and lower than that reported by Wu and coworkers (6.5% per patient, 0.23% per CMV-positive component). As discussed by Thiele and Wu, the CMV IgG detected in our patients likely represents passive antibody from recent transfusions. Our findings confirm those of Thiele and affirm the equivalent safety of CMV-U, leukoreduced components in CMV allogeneic HPC patients. The absence of clinical TT-CMV infection in our study and that by Thiele and coworkers, despite the combined transfusion of nearly 8000 CMV-U, leukoreduced components, contradicts sentiments from a past multivariate analysis, which advocated continued provision of CMV-N and leukoreduced components for CMV transplant patients. The improved safety of CMV-N over CMV-U, leukoreduced is also not supported by a recent large prospective study of 34,000 blood donors. Ziemann and colleagues found CMV viremia only among newly seroconverted donors and a few CMV-N donors, arguing that CMV-N components may present the higher risk of TT-CMV due to passive transfusion of free CMV DNA. In summary, policies stipulating leukoreduced, CMV-N components in CMV allogeneic HPC patients do not confer additional safety and are limited by product shortages and significant transfusion support required by many allogeneic HPC patients.