Platelet transfusions in adult patients with particular reference to patients undergoing surgery.

Descriptive information on platelet (PLT) recipients, particularly during surgery, is limited. A description of the current epidemiology of PLT-transfused patients is required to optimize platelet transfusion care and to follow trends in PLT use. In 2004 and 2005, information was combined from several computerized medical systems. Participating hospitals (9 hospital districts of 21) handled approximately 64% of annual Finnish hospital admissions. A total of 6321 adult patients were transfused with 37,761 PLT products. Most PLT products (43.1%) were transfused to patients suffering from haematological malignancies. Only 1.0% of all surgical patients received PLTs (53.8% of PLT recipients and 35.8% of transfused PLTs). The most common single operation connected with PLT transfusion was coronary artery bypass while 27.1% of surgery-related PLTs were given to patients having an operation involving the digestive system or spleen. Only 36.4% of all PLT-transfused (operated and conservatively treated) patients were discharged directly home; in-hospital mortality was 9.5%. PLTs were given 40 products per 1000 hospital admissions requiring an operation in 2004, and 38 products in 2005. Perioperative PLT use is slightly decreasing in adult patients. As a single-operation type, coronary artery bypass patients receive most of the PLT products and have experienced no decline in PLT use over the years. Overall, PLT recipients have high in-hospital mortality.

Development of permanent national register of blood component use utilizing electronic hospital information systems.

BACKGROUND AND OBJECTIVES: We wanted to establish a permanent national database system, which can be utilized to study transfusion recipients and blood use in Finland. MATERIALS AND METHODS: A regularly updated register for permanent use was developed. To study the usability of the database, years 2002 and 2003 were further analysed. Database included all transfused patients in major blood-transfusing hospitals from four university and five central hospital districts managing altogether 63% of Finnish inpatient hospital episodes. RESULTS: Audit of gathered data reveal 96.8% match in adult blood components with Finnish Red Cross, Blood Service sales figures. Model data set includes 59,535 transfused patients (44.3% men and 55.7% women) having received 529,104 blood components. Half of all blood units were transfused in connection with surgical operations. Most of the blood recipients were elderly (51.6% are over 64 years of age). Blood-component use and transfusion-related costs varied widely between hospitals. CONCLUSION: Hospital data managing systems can be useful for creating a population-based database system to monitor and compare transfusion practices. This record provides information about transfusion epidemiology for transfusion professionals, hospital management, and hospital administration.

Testosterone-induced growth of S115 mouse mammary tumor cells is dependent on heparan sulfate.

The androgen-induced proliferation of S115 mouse mammary tumor cells has been suggested to involve autocrinic fibroblast growth factor signaling. Heparan sulfate proteoglycans are required for fibroblast growth factor signaling, presumably due to their ability to alter binding of fibroblast growth factors to their receptors. We have investigated the role of heparan sulfate proteoglycans in the testosterone-induced proliferation of S115 cells. We demonstrate that when the cells are treated with sodium chlorate, which inhibits the sulfation of endogenous heparan sulfate proteoglycans, cell growth becomes dependent on exogenous heparin. The shortest heparin oligosaccharides supporting cell growth were octasaccharides, whereas dodecasaccharides were almost as effective as native heparin. The N-, 2-O-, and 6-O-sulfate groups of heparin were all required for full testosterone response. Treatment of S115 cells with chlorate or testosterone did not alter the expression of fibroblast growth factor receptors 1 or 3, whereas the expression of fibroblast growth factor receptor 2 was down-regulated. We have previously shown that overexpression of syndecan-1 heparan sulfate proteoglycan renders S115 cells insensitive to testosterone and now demonstrate that this effect can be overcome by sodium chlorate treatment in combination with exogenous heparin. Our results suggest that heparin-like molecules are intimately involved in the androgen-mediated proliferation of S115 cells.

Effects of alpha-interferon on serum beta-2-microglobulin.

Beta-2-microglobulin (B2M) forms the small invariable light chain subunit of class I HLA antigens on the cell membrane of all nucleated cells. During the continuous turnover of the HLA molecules, B2M is shed from the cell membrane into blood. Lymphocytes are the main source of serum free B2M. Serum B2M concentration is increased in renal diseases, various malignant diseases and some inflammatory and autoimmune disorders. In lymphatic malignancies serum B2M has significant prognostic value. Interferons (IFNs) have the ability to enhance the expression of class I and II histocompatibility antigens. Accordingly, IFNs cause a rise in formation and release of B2M. Currently, treatment with IFN alpha is used in diseases, like multiple myeloma, where serum B2M measurements are used to assess tumor burden. We have measured serum B2M levels during IFN alpha treatment in patients with both multiple myeloma and chronic myeloproliferative diseases, and IFN alpha caused a significant increase in serum B2M. It can be concluded that use of IFN alpha abolishes the value of serum B2M as an indicator of disease activity.

Soluble interleukin-6 receptor as a prognostic factor in multiple myeloma. Finnish Leukaemia Group.

Interleukin-6 (IL-6) is a major growth factor for the clonal malignant plasma cells in multiple myeloma (MM). The effect of IL-6 may be enhanced by soluble IL-6 receptor (sIL-6R). As there is a clinical need for improved stratification of MM patients at diagnosis, we have studied the role of sIL-6R as a prognostic marker in 207 newly diagnosed MM patients. Serum sIL-6R concentration was above the upper reference limit in 47% of the patients at diagnosis. The concentrations of sIL-6R and two other prognostic factors, IL-6 and beta-2 microglobulin (beta 2M), were all significantly higher in the patients who died within 3 years compared with those who survived. However, serum sIL-6R did not show linear correlation with IL-6 or beta 2M levels. In univariate logistic regression analysis sIL-6R was a significant predictor of 3-year mortality. Kaplan-Meier analysis showed that raised levels of sIL-6r were associated with shorter survival. When the patients were stratified into four groups according to their serum IL-6 and sIL-6R levels the patients with normal serum levels of both parameters had clear survival benefit. As beta 2M was the most powerful prognostic factor in the multivariate analysis, the patients were also stratified according to their serum beta 2M and sIL-6R levels. The patients with raised levels of both beta 2M and sIL-6R had shorter survival than the patients in the other three groups. Thus, measurement of these parameters at diagnosis would help to stratify MM patients.

Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group.

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.

Peripheral blood lymphocyte subsets in multiple myeloma and monoclonal gammopathy of undetermined significance.

Peripheral blood lymphocyte subsets were analysed by flow cytometry and compared among 43 patients with untreated multiple myeloma (MM), 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 26 controls. The age and sex distributions of the patients and controls were comparable, which is important, since in the controls there was a significant effect of age and/or sex on the number of CD3+, CD57+, CD8+57+, CD16+ and CD3-56+ lymphocyte subsets, and on the CD4+/CD8+ and CD4+Leu-8+/CD4+ ratios. In MM, the number of CD8+ and CD57+ cells and the CD4+/CD8+ ratio were related to the clinical stage. The number of CD20+, CD3+, CD4+, CD16+ and CD3-56+ cells and the CD3+/CD20+ ratio were significantly different in MM patients compared to age- and sex-matched controls as was the number of CD3+ and CD4+ cells of MGUS patients compared to controls. Further, there were significant differences in the CD3+/CD20+ ratio between MM and MGUS patients and between stage I MM and MGUS. The role of peripheral blood lymphocyte subsets in differentiating monoclonal gammopathies merits further study.

Serum immunoreactive interleukin-6 and C-reactive protein levels in patients with multiple myeloma at diagnosis.

Serum bioactive but not immunoreactive interleukin-6 (IL-6), and serum C-reactive protein (CRP), have been reported to be of prognostic significance in multiple myeloma (MM). We measured serum immunoreactive IL-6 by a sensitive enzyme-linked immunosorbent assay in 30 MM patients at diagnosis. In 30% of the patients serum immunoreactive IL-6 exceeded the upper reference limit. The concentrations of CRP and IL-6 showed a linear association. Logarithmically transformed IL-6, CRP and beta 2-microglobulin were significant variables by univariate survival analysis; by multivariate analysis CRP was a slightly stronger prognostic factor than IL-6 and the only one of independent prognostic significance.

Peripheral blood B lymphocytes in multiple myeloma.

Multiple myeloma (MM) is a disease of terminally differentiated B lineage cells and thus alterations in circulating B cells may be anticipated. We studied peripheral blood B cells by flow cytometry in 45 untreated MM patients and compared the results to 25 age-matched controls. The total lymphocyte count and the absolute number and percentage of CD20+ cells were significantly decreased in MM patients. Analysis of the relative amounts of CD20+ cells expressing surface immunoglobulin kappa or lambda light chain isotype did not show either clonal B cell excess or light chain isotype suppression. The percentages of CD10+ and CD20+10+ cells were low both in MM patients and in controls. We consider that the CD20+ cells analysed in this study mainly consisted of normal polyclonal B cells. However, the percentage of the CD20+ cells in the peripheral blood of MM patients was a prognostic factor for survival, both as a continuous and as a dichotomized variable.

Alpha interferon raises serum beta-2-microglobulin in patients treated for thrombocythaemia.

Serum beta-2-microglobulin (b2m) levels were studied in 10 patients treated with alpha interferon (IFN) for thrombocythaemia associated with chronic myeloproliferative diseases. In eight patients the IFN treatment decreased the blood platelet level to < 600 x 10(9)/l. Serum b2m levels rose significantly and dose-dependently immediately after the onset of treatment, by a median maximal increase of 72% with IFN 3 MU every other day, and 95% with 3 MU daily. The b2m rise caused by IFN abolishes the value of serum b2m in states where b2m is used as an indicator of disease activity.

Flow cytometric DNA analysis and clinical correlations in multiple myeloma.

DNA content of both bone marrow and peripheral blood mononuclear cells was measured by flow cytometric analysis in 46 patients with untreated multiple myeloma and 15 patients with benign monoclonal gammopathy to clarify further the incidence and clinical correlations of DNA aneuploidy. Aneuploidy was detected in the bone marrow of 25 multiple myeloma patients (54%) but in only one benign monoclonal gammopathy patient (7%), who developed multiple myeloma 34 months later. Thus DNA aneuploidy is considered rare in benign monoclonal gammopathy. In two multiple myeloma patients, DNA aneuploidy was detected also in blood, indicating circulating myeloma cells. The light chain of the M component was more frequently lambda in the diploid and kappa in the aneuploid group. Most of the patients with only light chain secretion were DNA aneuploid. Multiple myeloma patients with DNA hypodiploidy (7%), biclonal aneuploidy (4%), or DNA aneuploidy detectable in blood (4%) did not respond to therapy with melphalan and prednisone. Survival was not influenced by DNA content. No DNA aneuploidy was detected in the bone marrow or the peripheral blood of 26 patients with chronic lymphocytic leukemia or two patients with Waldenström's macroglobulinemia.

Alpha interferon raises serum beta-2-microglobulin in patients with multiple myeloma.

Serum beta 2-microglobulin (beta 2m) levels were followed in eight patients with multiple myeloma who were treated with leucocyte alpha interferon (alpha IFN) 6 x 10(6) IU daily for 1-2 weeks before chemotherapy. Serial measurements of serum beta 2m were carried out regularly during the first week on alpha IFN. A rise in beta 2m was observed in all patients. with maximum increments ranging from 29% to 185% (mean 109%). The increase in beta 2m was most marked in patients with elevated pretreatment levels of serum beta 2m and creatinine. In six patients the peak value was reached between the third and the fifth day, after which the levels decreased. In two patients serum beta 2m remained elevated for 3 and 4 months, respectively. A marked increase in serum beta 2m can be induced by alpha IFN in myeloma, which should be taken into consideration when using beta 2m for the assessment of tumour response during alpha IFN therapy.

Double monoclonal time-resolved immunofluorometric assay of beta 2-microglobulin in serum.

Previously reported immunochemical assays of beta 2-microglobulin (beta 2m) have usually been based on polyclonal antisera. We have developed a "sandwich"-type time-resolved immunofluorometric assay (TR-IFMA) for beta 2m in serum, based on two monoclonal antibodies against human beta 2m. Microtiter wells are coated with the capture antibody, and the tracer antibody is labeled with a europium chelate. In a simple and fast assay procedure, prediluted serum samples are incubated with the tracer for 1 h in the microtiter wells, after which the wells are washed and the fluorescence of Eu is measured. The mean analytical recovery was 101.8% and results by TR-IFMA showed a good linear correlation with those by an established radioimmunoassay. The analytical range of TR-IFMA is large and well suited for clinical purposes.

Four monoclonal immunoglobulins in a patient with chronic lymphocytic leukemia.

We report here the case of a 73-year-old woman with chronic lymphocytic leukemia. Two years after the diagnosis, electrophoresis of her serum showed two monoclonal fractions, but our modified immunofixation procedure revealed four monoclonal immunoglobulins in five fractions: two IgG lambda fractions, one IgG kappa fraction, one IgA kappa fraction, and one IgG kappa fraction. This is an exceptionally high number of monoclonal immunoglobulins in a single patient. In the course of her disease the patient did not show any clinical, radiological, or laboratory signs of multiple myeloma or macroglobulinemia. The different monoclonal immunoglobulins were considered to be one expression of her B-lymphocytic malignancy.