Expensive blood safety initiatives may offer less benefit than we think.

BACKGROUND: Various blood safety initiatives have ensured a historically low risk of infection transmission through blood transfusion. Although further prevention of infection transmission is possible through, for example, nucleic acid testing and future introduction of pathogen inactivation, such initiatives are very costly in relation to the benefit they offer. Although estimation of the cost-effectiveness requires detailed information about the survival of transfusion recipients, previous cost-effectiveness analyses have relied on incorrect survival assumptions. STUDY DESIGN AND METHODS: Based on empirical data of more than 1 million Scandinavian transfusion recipients followed for up to 20 years, we present two new survival functions. In a fictitious example we assessed the impact of survival assumptions on the estimated costs per quality-adjusted life-year (QALY) gained, by using the survival functions of three previous cost-effectiveness analyses along with the two new survival functions. CONCLUSIONS: We conclude that despite considerable costs, previous cost-effectiveness studies may have underestimated the costs per QALY gained by as much as 44%.

Should plasma from female donors be avoided? A population-based cohort study of plasma recipients in Sweden from 1990 through 2002.

BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion-related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population-based evidence, policies have already been introduced to exclude female donor plasma. STUDY DESIGN AND METHODS: Short-term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression. RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14-day mortality of 8.43%. Sixty-eight percent were exposed to female plasma, with a 14-day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06-1.27) and 1.32 (CI, 1.17-1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction. CONCLUSIONS: This large population-based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short-term survival disadvantage on recipients.

Blood transfusion exposure in Denmark and Sweden.

BACKGROUND: Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population. STUDY DESIGN AND METHODS: Population-based registry data of more than 600,000 transfusion recipients and general population data from 2000 to 2002 in Denmark and 1996 to 2002 in Sweden were reviewed. Outcome measures were the unit exposure rate, the 1-year period prevalence, the incidence rate, and the prevalence of exposure to blood transfusion. RESULTS: The unit exposure rate was 71.9 per 1000 population per year in Denmark and 60.9 in Sweden, corresponding to 29 percent more blood units being transfused in Denmark than in Sweden. The 1-year period prevalence was 8.8 and the incidence rate was 7.2 per 1000 population per year in Denmark, being 37 and 25 percent higher than in Sweden, respectively. The prevalences of blood transfusion in Danish males at 20, 40, 60, and 80 years of age were 1.9, 3.1, 7.6, and 18.1 percent, respectively. In Danish females, the corresponding prevalences were 1.6, 5.9, 11.1, and 20.5 percent. A similar but slightly lower prevalence was found in Sweden. CONCLUSION: Exposure to blood transfusion is frequent in Denmark and Sweden. At age 80 years, approximately one in five persons in the general population had received blood at least once.

Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study.

BACKGROUND: Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion. METHODS: We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors. FINDINGS: Of the 354 094 transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors. INTERPRETATION: Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.

Photopheresis for the treatment of refractory renal graft rejection.

Acute rejection episodes still occur after kidney transplantation in spite of modern immunosuppressive protocols including combined tacrolimus, mycophenolate mofetil, and prednisolone. The authors present seven cases of biopsy-proven acute rejection after kidney transplantation refractory to conventional rejection therapy with repeated pulses of high-dose steroids followed by polyclonal or monoclonal antibodies that responded well to photopheresis treatment. Photopheresis is an atoxic immunomodulatory apheresis-based treatment with no generalized immunosuppressive action; rather, it is directed at suppressing donor-specific T-cell clones. At the last follow-up, 9 to 43 months after transplantation, all patients had functioning grafts, with serum creatinine levels ranging from 105 to 312 microM. The authors conclude that photopheresis treatment contributed to the favorable outcome. Therefore, the authors are presently designing a prospective, randomized trial to evaluate the effect of photopheresis as an adjuvant prophylactic treatment after renal transplantation.

Storage of platelet concentrates from pooled buffy coats made of fresh and overnight-stored whole blood processed on the novel Atreus 2C+ system: in vitro study.

BACKGROUND: The Atreus 2C+ system (Gambro BCT) automatically separates whole blood (WB) into buffy coat (BC), red blood cells (RBC), and plasma and transfers the components into separate containers. After processing with the Atreus, 4 to 6 BC units can be pooled and processed into leukoreduced platelets (PLTs) by use of the automated OrbiSac BC system (Gambro BCT). The aim of our in vitro study was to investigate the effects of holding either WB or BC overnight before preparation of PLTs by use of the Atreus 2C+ system for BC preparation. A standard routine procedure involving conventional blood containers for the preparation of BC combined with the OrbiSac process (top-and-top system; Terumo) was used as a reference. STUDY DESIGN AND METHODS: WB was either processed within 8 hours after collection ("fresh blood") or stored overnight before processing. WB units were separated into BC, RBC, and plasma units and transferred into individual containers. Either the BC or the WB units rested overnight at 22 +/- 2 degrees C. Six ABO-identical BCs, obtained from either fresh or overnight-stored WB, were pooled and processed with the OrbiSac BC system to obtain leukoreduced PLTs. In total, 20 Atreus and 10 reference (leukoreduced PLTs) samples were analyzed for various in vitro variables during the 7-day storage period. RESULTS: No significant difference in glucose consumption, lactate production, mean PLT volume, LDH activity, bicarbonate, ATP, RANTES, and the expression of CD62p and CD42b between groups was detected. pH was maintained at greater than 7.0 (Day 7). Swirling remained at the highest levels (score, 2) for all units throughout storage. CONCLUSION: PLTs derived from BCs, obtained from either fresh or overnight-stored WB processed on the novel automated Atreus 2C+ system, were equivalent to control PLTs with regard to PLT in vitro characteristics during 7 days of storage. Stable recovery of PLTs and satisfactory PLT content according to current standards were also found.

Donation frequency, iron loss, and risk of cancer among blood donors.

BACKGROUND: Long-term deleterious effects of repeated blood donations may be masked by the donors' healthy lifestyle. To investigate possible effects of blood donation and iron loss through blood donation on cancer incidence while minimizing "healthy donor effects," we made dose-response comparisons within a cohort of Swedish and Danish blood donors. METHODS: We used a nested case-control study design, in which case patients were defined as all donors who were diagnosed with a malignancy between their first recorded blood donation and study termination (n = 10866). Control subjects (n = 107140) were individually matched on sex, age, and county of residence. Using conditional logistic regression, we estimated relative risks of cancer according to number of blood donations made or estimated iron loss 3-12 years before a case patient was diagnosed with cancer. All statistical tests were two-sided. RESULTS: No clear association was observed between number of donations and risk of cancer overall. However, between the lowest (< or = median, < 0.75 g) and highest (> 90th percentile, > 2.7 g) categories of estimated iron loss, there was a trend (P(trend) < .001) of decreasing risk for cancers of the liver, lung, colon, stomach, and esophagus, which are thought to be promoted by iron overload (combined odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.84), but only among men and only with a latency of 3-7 years. The risk of non-Hodgkin lymphoma was higher among frequent plasma donors (> 25 vs 0 donations, OR = 2.14, 95% CI = 1.22 to 3.74). CONCLUSIONS: Repeated blood donation was not associated with increased or decreased risk of cancer overall. The lack of consistency across latency periods casts doubt on an apparent association between reduced cancer risk and iron loss in men. The positive association between frequent plasma donation and risk of non-Hodgkin lymphoma deserves further exploration.

Major ABO blood group mismatch increases the risk for graft failure after unrelated donor hematopoietic stem cell transplantation.

Two hundred twenty-four patients with leukemia transplanted with an unrelated donor between 1991 and 2003 at the Karolinska University Hospital were analyzed according to association between graft failure and ABO, RhD, MNSs, and Kidd blood group antigen compatibility. Median age was 29 years (range: 0-55). Conditioning consisted of total-body irradiation or busulfan-based myeloablative conditioning. A bone marrow graft was given to 152 patients, and 72 patients received peripheral blood stem cells. Most patients received graft-versus-host disease prophylaxis with cyclosporine and MTX. Graft failure (GF) was seen in 6 (2.7%) patients. In the multivariate analysis major ABO mismatch (odds ratio [OR] 14.9, 95% confidence interval [CI] 2.01-110, P = .008) and HLA-allele mismatch (6.42, 1.19-34.8, P = .03) was significantly associated to GF. In patients with and without major ABO mismatch the incidence of GF was 7.5% and 0.6% (P = .02), respectively. Using an ABO major mismatched graft increases the risk for GF after unrelated donor hematopoietic stem cell transplantation.

Cancer incidence in blood transfusion recipients.

BACKGROUND: Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. METHODS: We used computerized files from Scandinavian blood banks to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided. RESULTS: During 5,652,918 person-years of follow-up, 80,990 cancers occurred in the transfusion recipients, corresponding to a SIR of 1.45 (95% confidence interval [CI] = 1.44 to 1.46). The SIR for cancer overall decreased from 5.36 (95% CI = 5.29 to 5.43) during the first 6 months after transfusion to 1.10 or less for follow-up periods more than 2 years after the transfusion. However, the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion. CONCLUSIONS: The marked increase in cancer risk shortly after a blood transfusion may reflect the presence of undiagnosed occult cancers with symptoms that necessitated the blood transfusion. The continued increased risk of tobacco- and alcohol-related cancers suggests that lifestyle and other risk factors related to conditions prompting transfusion rather than transfusion-related exposures per se are important to the observed cancer occurrence in the recipients.

Improving health profile of blood donors as a consequence of transfusion safety efforts.

BACKGROUND: Transfusion safety rests heavily on the health of blood donors. Although they are perceived as being healthier than average, little is known about their long-term disease patterns and to which extent the blood banks' continuous efforts to optimize donor selection has resulted in improvements. Mortality and cancer incidence among blood donors in Sweden and Denmark was investigated. STUDY DESIGN AND METHODS: All computerized blood bank databases were compiled into one database, which was linked to national population and health data registers. With a retrospective cohort study design, 1,110,329 blood donors were followed for up to 35 years from first computer-registered blood donation to death, emigration, or December 31, 2002. Standardized mortality and incidence ratios expressed relative risk of death and cancer comparing blood donors to the general population. RESULTS: Blood donors had an overall mortality 30 percent lower (99% confidence interval [CI] 29%-31%) and cancer incidence 4 percent lower (99% CI 2%-5%) than the background population. Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation. Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier. CONCLUSION: Blood donors enjoy better than average health. Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the selection of a particularly healthy subpopulation.

Storage of buffy coat-derived platelets in additive solutions: in vitro effects of storage at 4 degrees C.

BACKGROUND: The aims of this in vitro study were to compare the storage of platelets (PLTs) at 4 degrees C with those stored at 22 degrees C and to determine the in vitro effects of preincubation at 37 degrees C for 1 hour before the analysis on the basis of the maintenance of PLT metabolic and cellular integrity. STUDY DESIGN AND METHODS: PLT concentrates (PCs) were prepared from pooled buffy coats (BCs) for paired studies (total eight pools from 160 BCs). Each pool was divided into four PCs and stored under different conditions: at 20 to 24 degrees C on a flatbed agitator, at 20 to 24 degrees C on a flatbed agitator and with incubation of the samples at 37 degrees C for 1 hour before the analysis, at 4 degrees C, and at 4 degrees C and with incubation of the samples at 37 degrees C for 1 hour before the analysis. RESULTS: Storage of PLTs at 4 degrees C resulted in reductions in the rate of glycolysis and better retention of pH after Day 10 than in PCs stored at 22 degrees C (Day 14, 7.003 +/- 0.047 vs. 7.201 +/- 0.146). Hypotonic shock response and extent of shape change were higher at 22 degrees C than at 4 degrees C and in preincubated PCs stored at 22 degrees C than in reference PCs stored at the same temperature (Day 5, 45.6 +/- 2.7 vs. 36.5 +/- 3.9 and 24.1 +/- 2.0 vs. 15.5 +/- 1.8). The concentration of RANTES was higher in PCs stored at 22 degrees C than at 4 degrees C (Day 7, 179 +/- 25 vs. 79 +/- 32). CONCLUSION: PLTs stored at 4 degrees C without agitation maintain metabolic and cellular characteristics to a great extent during 21 days of storage. These studies confirm the view that PLTs lose their discoid shape and that this loss with storage at 4 degrees C is associated with reductions in metabolic rate and in their release of alpha-granule content.

Paired in vitro and in vivo comparison of apheresis platelet concentrates stored in platelet additive solution for 1 versus 7 days.

BACKGROUND: To improve clinical access to platelet concentrates (PCs), prolonging the storage period is one alternative, provided that they are free from bacteria. The quality of platelets (PLTs) stored for 1 versus 7 days was compared by in vitro analyses and in vivo recovery and survival in blood donors. STUDY DESIGN AND METHODS: Apheresis PCs from 10 donors were divided and stored in PLT additive solution in 2 equal units for a paired comparison. PLTs in one unit were (111)In-labeled at 1 day of storage, and PLTs in the other unit were labeled after 7 days of storage. PLTs were injected into the donor after labeling and samples were drawn after 30, 60, and 150 minutes and thereafter once a day for 14 days for recovery and survival measurements. RESULTS: PLT recovery on Day 7 was 80 percent of the recovery on Day 1 (p<0.05), and the survival on Day 7 was 65 percent of survival on Day 1 (p<0.005). No significant differences were seen regarding mean PLT volume (MPV), pH, pCO2, pO2, bicarbonate, or hypotonic shock response. Lactate increased and lactic dehydrogenase increased slightly, whereas glucose and ATP decreased, but not to a critical level. A significant increase in RANTES (110.7+/-76.6 vs. 277.6+/-50.8 pg/10(6) PLTs [p<0.005]) and PLT factor 4 (19.9+/-9.6 vs. 59.8+/-7.5 IU/10(6) PLTs [p<0.0001]) was noticed during storage. CONCLUSION: Recovery and survival of PCs stored for 7 days decreased, but met suggested criteria. Analyzed in vitro parameters showed acceptable results. Randomized patient transfusion studies will provide additional verification of the suitability of 7-day storage of PLTs.

A prospective randomized trial of a prophylactic platelet transfusion trigger of 10 x 10(9) per L versus 30 x 10(9) per L in allogeneic hematopoietic progenitor cell transplant recipients.

BACKGROUND: The impact of lowering the platelet (PLT) count threshold for prophylactic PLT transfusion on bleeding and PLT use in allogeneic hematopoietic progenitor cell (HPC) transplant recipients is a matter of debate. STUDY DESIGN AND METHODS: In 166 patients, randomly assigned to receive prophylactic PLT transfusion at a trigger level less than 10 x 10(9) PLTs per L (T10; n = 79) or less than 30 x 10(9) per L (T30; n = 87), the number of PLT and red blood cell (RBC) transfusions given and the number of hemorrhagic events (WHO Grades 2-4) were recorded. RESULTS: No significant differences were found between the two groups regarding the clinical outcome variables (i.e., bacteremia, engraftment, graft-vs.-host disease [GVHD], hospital stay, death, and survival) or in the median total number of RBC transfusions given. The incidence, in Group T10 18 percent (14/79) and in Group T30 15 percent (13/87), as well as the type of bleeding were comparable. No deaths were attributed to hemorrhages. The number of PLT units transfused, however, was significantly lower in Group T10 (median, 4; range, 0-32), than in Group T30 (median, 10; range, 0-48; p < 0.001). Apart from the trigger level, the day of engraftment, the presence of acute GVHD, or bacteremia also affected the number of PLT transfusions. CONCLUSION: A prophylactic PLT transfusion trigger level of less than 10 x 10(9) PLTs per L instead of less than 30 x 10(9) PLTs per L in allogeneic HPC transplant recipients was found to be safe and resulted in a decreased use of PLTs.

Experiences with fetomaternal alloimmune thrombocytopenia at a Swedish hospital over a 10-year period.

BACKGROUND: This is a descriptive study of the management and outcome of 18 cases of fetomaternal alloimmune thrombocytopenia (FMAIT) treated from 1991 to 2001. MATERIAL AND METHODS: Management of the disease changed over the years from cordocentesis in the 20-24th week of gestation, platelet transfusions and immunoglobulin to a less invasive management consisting of only blind administration of immunoglobulin and predelivery cordocentesis. RESULTS: Three of the fetuses were treated with intrauterine platelet transfusions. Two of these were delivered by emergency cesarean section due to failed transfusions and the third fetus died as a result of the procedure. Nine mothers were treated with immunoglobulin intravenously. Four of these delivered thrombocytopenic children. Three women did not want to undergo any treatment, and all newborns had low platelet counts. Two fetuses died, one in conjunction with a platelet transfusion and the other in utero before treatment was commenced. All the other children did well despite the fact that some of them were severely thrombocytopenic at birth. CONCLUSIONS: Due to the limited number of patients, the present material does not allow any far reaching conclusions. Our experience is that a non-invasive management can be practiced in cases of FMAIT. The value of performing cordocentesis and platelet transfusions in the second trimester is doubtful in view of the risk for the fetus and the limited amount of information it provides for management of the individual case.