An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study.

BACKGROUND: Typical practice is to transfuse group-specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world. STUDY DESIGN AND METHODS: The study had two phases: a survey that inquired about hospital group AB plasma inventory, policies, and transfusion practices and a retrospective review of 2014 calendar year data where participants submitted information on plasma disposition including ABO group of unit and recipient, transfusion location, and select indications. Recruitment occurred through snowball sampling. Descriptive analyses were performed. RESULTS: Survey data were received from 25 centers across 10 countries; of those, 15 participants contributed to the data collection component. These 15 centers transfused a total of 43,369 AB plasma units during the study period. Only 1496 of 5541 (27%) group AB plasma units were transfused to group AB recipients. Transfusion policies, practices, and patterns were variable across sites. CONCLUSION: Group AB plasma units are frequently transfused to non-AB recipients. Whether transfusing 73% of group AB plasma units to non-AB recipients is the ideal inventory management strategy remains to be determined.

An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.

BACKGROUND: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. STUDY DESIGN AND METHODS: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. RESULTS: Thirty-eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non-O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non-group O D- patients ranging from 0% to 33%. CONCLUSION: A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites.

An international survey on the role of the hospital transfusion committee.

BACKGROUND: Hospital transfusion committees (HTCs) can oversee all aspects of transfusion practice at a hospital. This survey sought to identify which quality variables were being reported at HTCs around the world. STUDY DESIGN AND METHODS: A working party composed of members of the Biomedical Excellence for Safer Transfusion (BEST) collaborative developed a survey of quality variables that could be potentially presented at HTC meetings. The survey was electronically sent to all BEST members who were encouraged to complete it if they were active on an HTC and to send it to other colleagues with similar experience. An expert panel was convened to determine which quality variables are the most important for review at HTC meetings. RESULTS: There were 121 respondents; the majority were from Europe (52%), Asia (19%), or North America (19%). Most respondents (68%) were at university hospitals. Of the 117 (97%) respondents with an HTC, the committee most often met quarterly (42%) and reviewed transfusion reactions (79%) and risk management-reported events (52%). The HTCs most commonly included transfusion medicine physicians, anesthesiologists, and other physicians who regularly transfuse blood products. Some of the most commonly reported quality variables included number of blood products transfused, wasted, and expired and the number of improperly labeled specimens. The expert panel analysis revealed that some variables that were deemed important were not being frequently reported at HTCs. CONCLUSION: There is variability in the variables being reported at HTCs around the world with some important variables not frequently reported.

The Crossmatch/Issue Ratio: Use of a Novel Quality Indicator and Results of an International Survey on RBC Crossmatching and Issuing Practices.

OBJECTIVES: To understand the worldwide scope of RBC crossmatching and issuing practices and measure efficiency using a novel quality indicator, the crossmatch/issue (C/I) ratio. METHODS: An electronic survey was disseminated to hospital transfusion services collecting details about RBC crossmatching and issuing practices. Respondents were asked to enumerate the number of RBCs crossmatched and issued at their institutions during the 2014 calendar year to calculate the C/I ratio. RESULTS: Fifty-two survey responses were received, mostly from North American transfusion services (28/52, 54%). The electronic crossmatch was the most common technique (n = 29), and most respondents performed the crossmatch at the time that an order for RBCs was received in the transfusion service (even if an order to issue the RBCs was not received). Data to calculate the C/I ratio were supplied by 22 respondents, and the mean ± SD was 1.30 ± 0.34. There was no difference in C/I ratios between services that use the electronic or serologic crossmatch techniques (P = .49). The ratio was the same at the four sites that crossmatch RBCs at the time of issue compared with the time of order receipt (mean ± SD, 1.11 ± 0.09 vs. 1.35 ± 0.36, respectively; P = .19). CONCLUSIONS: Electronic crossmatching is common, and the C/I ratio can be an indicator of efficiency.

[Emerging infectious diseases in the context of blood safety]. / Nowo pojawiajace sie choroby zakazne w aspekcie bezpieczenstwa krwi.

The risk of transfusion-related infectious diseases, the markers for which are routinely tested, is extremely low. Recently, however, blood transfusion service faces the challenge from emerging infectious diseases (EIDs), mainly zoonotic origin. Pathogens are microorganisms, mostly viruses, that usually require vectors for their transmission to humans. The relation of some EIDs to transfusion has been proved, in other cases it is considered likely. The paper presents views on EIDs etiology and spread and explains the epidemiologic basic terminology. It describes the principles and methods of EIDs risk assessment as well as prioritization of EIDs with regard to transfusion risk. It outlines the principles of international cooperation and rapid response to newly emerging threats. More attention is devoted to such diseases as West Nile fever, malaria, dengue and chikungunya which are recently a real epidemiological threat. Preventive measures to reduce the threat of EIDs transmission have also been discussed as well as their impact on the safety and supply of blood and blood components.

Babesia spp. infections transmitted through blood transfusion.

Babesiosis in humans is caused by infection with various species of Babesia (Apicomplexa, Piroplasmida), mainly transmitted by an arthropod vector--Ixodes spp. ticks. This review will focus on blood transfusion as another mode of Babesia transmission, especially in endemic areas, as well as the impact of human babesiosis on transfusion medicine.

Flow cytometric immunophenotypic characteristics of plasma cell leukemia.

The aim of this prospective study was to define the flow cytometric characteristics of simultaneously investigated bone marrow and peripheral blood plasma cells antigens expression in 36 plasma cell leukemia (PCL) patients. The immunophenotypic profile of plasma cells was determined with a panel of monoclonal antibodies. The antigen expression intensity was calculated as relative fluorescence intensity (RFI). Bone marrow plasma cells showed expression of particular antigens in the following proportion of cases: CD49d 100%, CD29 94%, CD54 93%, CD44 83%, CD56 60%, CD18 26%, CD11b 29%, CD11a 19%, CD117 27%, CD71 30%, CD126 100% and CD19 0%, while the expression of those antigens on peripheral blood plasma cells was present in the following percentage of patients: CD49d 100%, CD29 96%, CD54 93%, CD44 95%, CD56 56%, CD18 50%, CD11b 53%, CD11a 29%, CD117 26%, CD71 28%, CD126 100% and CD19 0%. The expression of CD54 was significantly higher than that of adhesion molecules belonging to the integrin b2 family: CD11a, CD18 and CD11b, on both bone marrow and peripheral blood cells (p < 0.01). Expression of CD18, CD11a and CD11b was differential between two cell compartments: lower on bone marrow and higher on peripheral blood cells. We found that plasma cells in the bone marrow of patients with plasma cell leukaemia showed significantly greater granularity and size than those in the peripheral blood (p = 0.0001 and p = 0.04, respectively). However, no differences in cell size or granularity were revealed between bone marrow plasma cells from patients with PCL and multiple myeloma. In conclusion, impaired expression of adhesion molecules such as CD11a/CD18 (LFA-1) or CD56 may explain hematogenic dissemination characterizing PCL. The following pattern of adhesion molecule expression according to the proportion of plasma cells expressing a given antigen in peripheral blood and bone marrow and arranged in diminishing order may be established: CD49d > CD44 > CD54 > CD29 > CD56 > CD18 > CD11b > CD11a. Immuno-phenotyping of plasma cells in PCL, as in multiple myeloma, might be useful in detecting minimal residual disease in cases with aberrant antigen expression and for selecting therapeutic agents towards specific membrane targets.

Flow cytometric immunophenotypic characteristics of 36 cases of plasma cell leukemia.

Prospective flow cytometric analysis of antigens expression on bone marrow and peripheral blood plasma cells of 36 plasma cell leukemia (PCL) patients enabled to establish the following immunophenotype of leukemic plasma cell: CD38(++), CD138(+), CD54(+), CD49d(+), CD29(+), CD44(+), CD126(+), CD19(-), CD45(-). In one-third of patients PCL cells express CD56, CD71 and CD117. Expression of CD54 on plasma cells was higher as compared to expression of adhesion molecules CD11a, CD18 and CD11b (p<0.01). Expression of CD18, CD11a, CD11b was lower on bone marrow and higher on peripheral blood cells. In conclusion, impaired expression of adhesion molecules such as CD11a/CD18 or CD56 may explain hematogenic dissemination characterizing PCL.

Clinicopathological correlates of plasma cell CD56 (NCAM) expression in multiple myeloma.

The aim of this prospective, long-term study was to define the flow cytometric characteristics of plasma cell CD56 expression as well as determine the clinical characteristics of 204 multiple myeloma (MM) patients and 26 plasma cell leukemia (PCL) patients with regard to CD56 expression. CD56 expression intensity was determined by measurement of antigen molecules on the cell defined as Antibodies Bound per Cell (ABC) and calculation of Relative Fluorescence Intensity (RFI). CD56 expression was found in 66% of MM and 54% of PCL cases. The RFI values for individual MM patients ranged from 7.6 to 27.4 while ABC values on MM plasma cells from 2255 to 58469. There was a correlation between the proportion of all bone marrow CD38(++)/CD138(+) cells with CD56 expression and ABC and RFI indices. With regard to CD56 expression positive patients, the CD56(-) MM patients presented lower frequency of osteolysis (p = 0.01). The median survival was 48 months in CD56(+) patients and 43 months (p = 0.84) in CD56(-) cases. In conclusion, CD56 expression carries no distinct adverse prognosis and the lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM. A remarkable heterogeneity of CD56 expression intensity in CD56(+) patients imposes the necessity of determining CD56 expression intensity in candidates to antibody-based therapy.

Correlation of osteoprotegerin and sRANKL concentrations in serum and bone marrow of multiple myeloma patients.

INTRODUCTION: Recent studies suggest that multiple myeloma (MM) triggers osteoclastogenesis by disrupting the balance between the receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), its natural antagonist. MATERIAL/METHODS: Determinations of bone marrow (BM) and serum OPG and sRANKL concentrations were performed in 133 MM patients and 42 healthy subjects by the ELISA method using Osteoprotegerin ELISA and sRANKL ELISA kits. RESULTS: MM patients had elevated serum levels of OPG compared with controls (p<0.0001) and OPG levels were higher in patients with renal failure and patients with hipercalcemia (p<0.001 and p=0.04, respectively). Serum OPG levels correlated with age, serum beta 2-microglobulin, and BM OPG concentrations and did not correlate with the presence of osteolysis or with stage of disease. sRANKL serum levels in MM patients and in controls were not statistically different (p=0.42). In MM patients, serum OPG and sRANKL levels were similar at diagnosis and in the plateau phase of disease. There was a correlation between BM and serum sRANKL concentrations (p<0.001). Median values of the sRANKL/OPG ratio for BM and serum of MM patients were 0.14 and 0.11, respectively. The median value of the sRANKL/OPG ratio for the serum of controls was 0.11. CONCLUSIONS: In 20% of MM patients, serum OPG levels are elevated, and this may be a compensative reaction related to increased bone destruction. There is not statistically significant relationship between sRANKL serum and BM levels and the main clinical and laboratory parameters of the disease. Determination of BM and the serum sRANKL/OPG ratio seems to have no clinical value.

C-kit receptor (CD117) expression on plasma cells in monoclonal gammopathies.

The surface expression of CD117 antigen (c-kit) on plasma cells from 158 multiple myeloma (MM), 12 plasma cell leukemia (PCL), 7 MGUS, 7 IgM lymphoplasmacytic lymphoma patients and 10 healthy subjects has been analyzed by flow cytometry using triple staining with the monoclonal antibodies CD138, CD117 and CD38. The antigen expression intensity was calculated as relative fluorescence intensity (RFI) and for direct quantitative analysis the QuantiBRITE test (Becton Dickinson) was applied. Antibody bounding capacity (ABC) was calculated using QuantiCALC software. CD117 antigen was present in 49/158 MM, 5/12 PCL and 5/7 MGUS patients. The RFI values ranged from 0.2 to 20.2 in particular MM patients (mean: 11.0+/-5.3; median 11.5) while the number of CD117 binding sites (ABC) on MM plasma cells ranged from 637 to 6217 (mean: 3029+/-1568; median 2946) (r=0.8328). In responsive to chemotherapy c-kit positive MM patients the percentage of CD117+ plasma cells in the bone marrow decreased significantly while in c-kit negative MM patients the percentage of CD117+ cells in bone marrow did not change and remained in the normal limits. When comparing the clinical and biological disease characteristics (monoclonal protein isotype, albumin, beta2-microglobulin, lactate dehydrogenase, stage of disease, response to chemotherapy, survival time) of c-kit positive and c-kit negative cases, no significant differences were found. In CD117 positive PCL cases expression of CD117 was detected in bone marrow plasma cells as well as in peripheral blood plasma cells. Normal plasma cells and those in IgM lymphoplasmacytic lymphoma did not show reactivity for the CD117 antigen. We conclude that it may be rationale to consider usefulness of therapy with tyrosine kinase inhibitors in the management of c-kit positive plasma cell proliferations. In one third of MM and PCL patients c-kit antigen could be considered as a "tumor associated marker" and together with CD38 and CD138 it may be of value for the identification of the malignant clone in minimal residual disease as it was first suggested by Spanish authors.

Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience).

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.