The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the ... more The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.
To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate ... more To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may result in a hemolytic reaction, we conducted a prospective longitudinal study in which 10 patients transfused with 1 unit of G6PD-deficient and 1 unit of normal red blood cells (RBC) were compared with 10 patients transfused with 2 units of age-matched normal RBC. We found that 24 h after transfusion serum bilirubin (mumol/l) in the recipients of G6PD-deficient RBC was significantly higher than in the recipients of normal RBC (36 +/- 14 vs. 18 +/- 5, respectively, p > 0.004). A parallel increase was found in the serum lactate dehydrogenase (LDH; IU/l) between the two groups (378 +/- 151 vs. 264 +/- 56, p < 0.001). The difference in serum bilirubin (26 +/- 10 vs. 15 +/- 5, p < 0.03) was still noted 48 h after transfusion, with only a marginal difference (p < 0.08) in LDH. We conclude that an immediate posttransfusional hemolytic reaction can occur in recipients of G6PD-deficient RBC and therefore suggest that the differential diagnosis of posttransfusional hemolysis, particularly in populations where G6PD deficiency is prevalent, includes transfusion of erythrocytes from G6PD-deficient donors.
... Fulminant Hepatic Failure Rifaat Safadi a , Koray Ergunay a,c , Yaron Ilan a , Athalia Klein ... more ... Fulminant Hepatic Failure Rifaat Safadi a , Koray Ergunay a,c , Yaron Ilan a , Athalia Klein a , Daniel Shouval a , Noga Manny b , Nissim ... Simmonds P, Davidson F, Lycett C, Prescott LE, MacDonald DM, Ellender J, Yap PL, Ludlam CA, Haydon GH, Gillon J, Jarvis LM: Detection ...
Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. Th... more Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. This long-standing fascination with chimeras has revealed a good deal of knowledge about human inheritance. Although historically most chimeras were caused by natural events, certain current medical intervention therapies are increasing the number of situations that can lead to a mixed cell population, that is, the chimeric condition, in humans. Medical therapies such as transfusion, stem cell transplantation, kidney transplantation, and artificial insemination induce temporary and sometimes permanent chimeras. Such natural or therapeutically induced presentations of chimerism can present challenging issues to the clinical immunohematology laboratory with regard to interpretation of results and subsequent patient management. The purpose of this review was to highlight some of these chimeric states and hypothesize how testing DNA from various tissues can cause apparent discrepancies between phenotype and genotype results.
Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and ... more Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and adherence to endothelial cells, play major roles in blood circulation. Their impairment, as occurs under various blood banking conditions, may contribute to circulatory impairment in recipients. Recent studies and meta-analyses show that the transfusion of stored RBCs (stRBCs) may be less beneficial than that of freshly collected units, which may thus adversely affect recipients, especially their circulatory function, thereby pointing to a potential role in the alteration of FPs of stRBCs. In this review, we present an up-to-date summary of the studies on the FP of stRBCs, clearly showing that they may be impaired at an early stage of storage, which may contribute considerably to transfusion-associated circulatory impairment in recipients. The alteration of the FPs of stRBC is attenuated by prestorage leukoreduction and/or poststorage "rejuvenation." However, because these procedures, especially rejuvenation, are costly and are associated with an increased risk of bacterial contamination, there is an urgent need to establish better methods of improving the hemodynamic function of stRBCs before their transfusion. It is therefore proposed that the FPs of stRBC may be important measures of the outcome of RBC transfusions. Monitoring such functions would thereby introduce necessary criteria and new tools for the quality control of stRBC units, making an important contribution to transfusion therapy.
Storage of blood units (for 35-42 days, depending on the preservative solution) has been reported... more Storage of blood units (for 35-42 days, depending on the preservative solution) has been reported to induce changes (e.g., reduction of sialic acid level) in red cells that are expected to alter their aggregability. The aggregability of stored red cells was monitored in their autologous plasma and compared to that obtained with washed cells in dextran-containing buffer throughout the storage period. Red cell aggregability was determined by using a computerized image analyzer of cell flow properties. Blood storage induced changes in red cells that are associated with continuous increase of their aggregability. At the same time, blood storage was associated with a reduction in the level of plasma fibrinogen, the major aggregating agent in plasma. Accordingly, the increased red cell aggregability was observed in red cells stored in dextran-containing buffer, but not in red cells stored in autologous plasma. Because blood transfusion is routinely given to patients with normal or high fibrinogen level, the transfusion of stored red cells has the potential to induce increased aggregation in vivo, depending on the storage period. This should be taken into account when blood transfusion is considered, particularly for patients with microcirculatory disorders.
Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and ar... more Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and are of uncertain clinical significance. Three patients were encountered in whom anti-Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two-unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance. Although anti-Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti-Lu6 should be performed cautiously.
To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection a... more To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection among employees of a large hospital in Israel. Seroprevalence survey. A 1,006-bed, tertiary-care university hospital in Jerusalem. All 5,444 employees (18-65 years old) were eligible; 4,287 (79%) participated in the survey. Sera were tested for antibodies to HCV (anti-HCV) using a third-generation enzyme immunoassay. A third-generation strip immunoblot assay was used for confirmation. Participants were interviewed regarding their occupational history, and they completed a self-administered questionnaire covering history of non-occupational exposure to blood and country of birth. Other demographic information was obtained from the personnel department. Rates and odds ratios (ORs) were calculated, and multivariate logistic-regression analyses were performed to adjust for potential confounding variables. Anti-HCV was found in 0.9% of employees (37/4,287; 95% confidence interval, 0.6-1.1), ranging from 0.1% among those born in Israel to 5.7% among those born in Central Asia. After age, gender, social status, country of birth, and history of blood transfusion were controlled for in a logistic regression, occupational exposure to blood > or = 10 years was significantly associated with the presence of antibodies (OR, 2.6; P=.01). Presence of anti-HCV also was associated with country of birth (range: Israel OR, 1; West OR, 3.8 [P=.1]; Central Asia OR, 48.6 [P<.0001]) and history of blood transfusion (OR, 2.7; P=.01). No significant associations were found between anti-HCV and age, gender, social status, history of tattoo, acupuncture, current occupation, department, exposure to blood in current occupation, adherence to safety precautions, or history of percutaneous injury. The association with length of exposure was stronger (OR, 3.6; P=.01) when the same logistic regression was run excluding the outlier ethnic group of Central Asia. Hospital work does not seem to constitute a major risk factor for HCV infection in Israel today. A higher prevalence of anti-HCV among employees with longer versus shorter lengths of occupational exposure may be due to a cumulative effect of exposure over the years. Infection control efforts in recent years may have contributed to this association.
One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received a... more One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.
The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the ... more The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.
To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate ... more To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may result in a hemolytic reaction, we conducted a prospective longitudinal study in which 10 patients transfused with 1 unit of G6PD-deficient and 1 unit of normal red blood cells (RBC) were compared with 10 patients transfused with 2 units of age-matched normal RBC. We found that 24 h after transfusion serum bilirubin (mumol/l) in the recipients of G6PD-deficient RBC was significantly higher than in the recipients of normal RBC (36 +/- 14 vs. 18 +/- 5, respectively, p > 0.004). A parallel increase was found in the serum lactate dehydrogenase (LDH; IU/l) between the two groups (378 +/- 151 vs. 264 +/- 56, p < 0.001). The difference in serum bilirubin (26 +/- 10 vs. 15 +/- 5, p < 0.03) was still noted 48 h after transfusion, with only a marginal difference (p < 0.08) in LDH. We conclude that an immediate posttransfusional hemolytic reaction can occur in recipients of G6PD-deficient RBC and therefore suggest that the differential diagnosis of posttransfusional hemolysis, particularly in populations where G6PD deficiency is prevalent, includes transfusion of erythrocytes from G6PD-deficient donors.
... Fulminant Hepatic Failure Rifaat Safadi a , Koray Ergunay a,c , Yaron Ilan a , Athalia Klein ... more ... Fulminant Hepatic Failure Rifaat Safadi a , Koray Ergunay a,c , Yaron Ilan a , Athalia Klein a , Daniel Shouval a , Noga Manny b , Nissim ... Simmonds P, Davidson F, Lycett C, Prescott LE, MacDonald DM, Ellender J, Yap PL, Ludlam CA, Haydon GH, Gillon J, Jarvis LM: Detection ...
Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. Th... more Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. This long-standing fascination with chimeras has revealed a good deal of knowledge about human inheritance. Although historically most chimeras were caused by natural events, certain current medical intervention therapies are increasing the number of situations that can lead to a mixed cell population, that is, the chimeric condition, in humans. Medical therapies such as transfusion, stem cell transplantation, kidney transplantation, and artificial insemination induce temporary and sometimes permanent chimeras. Such natural or therapeutically induced presentations of chimerism can present challenging issues to the clinical immunohematology laboratory with regard to interpretation of results and subsequent patient management. The purpose of this review was to highlight some of these chimeric states and hypothesize how testing DNA from various tissues can cause apparent discrepancies between phenotype and genotype results.
Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and ... more Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and adherence to endothelial cells, play major roles in blood circulation. Their impairment, as occurs under various blood banking conditions, may contribute to circulatory impairment in recipients. Recent studies and meta-analyses show that the transfusion of stored RBCs (stRBCs) may be less beneficial than that of freshly collected units, which may thus adversely affect recipients, especially their circulatory function, thereby pointing to a potential role in the alteration of FPs of stRBCs. In this review, we present an up-to-date summary of the studies on the FP of stRBCs, clearly showing that they may be impaired at an early stage of storage, which may contribute considerably to transfusion-associated circulatory impairment in recipients. The alteration of the FPs of stRBC is attenuated by prestorage leukoreduction and/or poststorage "rejuvenation." However, because these procedures, especially rejuvenation, are costly and are associated with an increased risk of bacterial contamination, there is an urgent need to establish better methods of improving the hemodynamic function of stRBCs before their transfusion. It is therefore proposed that the FPs of stRBC may be important measures of the outcome of RBC transfusions. Monitoring such functions would thereby introduce necessary criteria and new tools for the quality control of stRBC units, making an important contribution to transfusion therapy.
Storage of blood units (for 35-42 days, depending on the preservative solution) has been reported... more Storage of blood units (for 35-42 days, depending on the preservative solution) has been reported to induce changes (e.g., reduction of sialic acid level) in red cells that are expected to alter their aggregability. The aggregability of stored red cells was monitored in their autologous plasma and compared to that obtained with washed cells in dextran-containing buffer throughout the storage period. Red cell aggregability was determined by using a computerized image analyzer of cell flow properties. Blood storage induced changes in red cells that are associated with continuous increase of their aggregability. At the same time, blood storage was associated with a reduction in the level of plasma fibrinogen, the major aggregating agent in plasma. Accordingly, the increased red cell aggregability was observed in red cells stored in dextran-containing buffer, but not in red cells stored in autologous plasma. Because blood transfusion is routinely given to patients with normal or high fibrinogen level, the transfusion of stored red cells has the potential to induce increased aggregation in vivo, depending on the storage period. This should be taken into account when blood transfusion is considered, particularly for patients with microcirculatory disorders.
Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and ar... more Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and are of uncertain clinical significance. Three patients were encountered in whom anti-Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two-unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance. Although anti-Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti-Lu6 should be performed cautiously.
To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection a... more To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection among employees of a large hospital in Israel. Seroprevalence survey. A 1,006-bed, tertiary-care university hospital in Jerusalem. All 5,444 employees (18-65 years old) were eligible; 4,287 (79%) participated in the survey. Sera were tested for antibodies to HCV (anti-HCV) using a third-generation enzyme immunoassay. A third-generation strip immunoblot assay was used for confirmation. Participants were interviewed regarding their occupational history, and they completed a self-administered questionnaire covering history of non-occupational exposure to blood and country of birth. Other demographic information was obtained from the personnel department. Rates and odds ratios (ORs) were calculated, and multivariate logistic-regression analyses were performed to adjust for potential confounding variables. Anti-HCV was found in 0.9% of employees (37/4,287; 95% confidence interval, 0.6-1.1), ranging from 0.1% among those born in Israel to 5.7% among those born in Central Asia. After age, gender, social status, country of birth, and history of blood transfusion were controlled for in a logistic regression, occupational exposure to blood > or = 10 years was significantly associated with the presence of antibodies (OR, 2.6; P=.01). Presence of anti-HCV also was associated with country of birth (range: Israel OR, 1; West OR, 3.8 [P=.1]; Central Asia OR, 48.6 [P<.0001]) and history of blood transfusion (OR, 2.7; P=.01). No significant associations were found between anti-HCV and age, gender, social status, history of tattoo, acupuncture, current occupation, department, exposure to blood in current occupation, adherence to safety precautions, or history of percutaneous injury. The association with length of exposure was stronger (OR, 3.6; P=.01) when the same logistic regression was run excluding the outlier ethnic group of Central Asia. Hospital work does not seem to constitute a major risk factor for HCV infection in Israel today. A higher prevalence of anti-HCV among employees with longer versus shorter lengths of occupational exposure may be due to a cumulative effect of exposure over the years. Infection control efforts in recent years may have contributed to this association.
One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received a... more One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.
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