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1.  Low-Density Lipoprotein Apheresis 
Executive Summary
Objective
To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH).
Background on Familial Hypercholesterolemia
Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death.
Familial hypercholesterolemia occurs in both HTZ and HMZ forms.
Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals1. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario.
In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death.
In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol/L or 500-1000mg/dL). Homozygous FH patients are typically diagnosed in infancy, usually due to the presence of cholesterol deposits in the skin and tendons. The main complication of HMZ FH is supravalvular aortic stenosis, which is caused by cholesterol deposits on the aortic valve and in the ascending aorta. The average life expectancy of affected individuals is 23 to 25 years. In Ontario, it is estimated that there are 13 to 15 cases of HMZ FH. An Ontario clinical expert confirmed that 9 HMZ FH patients have been identified to date.
Diagnosis
There are 2 accepted clinical diagnostic criterion for the diagnosis of FH: the Simon Broome FH Register criteria from the United Kingdom and the Dutch Lipid Network criteria from the Netherlands. The criterion supplement cholesterol levels with clinical history, physical signs and family history. DNA-based-mutation-screening methods permit a definitive diagnosis of HTZ FH to be made. However, given that there are over 1000 identified mutations in the LDL receptor gene and that the detection rates of current techniques are low, genetic testing becomes problematic in countries with high genetic heterogeneity, such as Canada.
Treatment
The primary aim of treatment in both HTZ and HMZ FH is to reduce plasma LDL-C levels in order to reduce the risk of developing atherosclerosis and CAD.
The first line of treatment is dietary intervention, however it alone is rarely sufficient for the treatment of FH patients. Patients are frequently treated with lipid-lowering drugs such as resins, fibrates, niacin, statins and cholesterol absorption-inhibiting drugs (ezetimibe). Most HTZ FH patients require a combination of drugs to achieve or approach target cholesterol levels.
A small number of HTZ FH patients are refractory to treatment or intolerant to lipid-lowering medication. According to clinical experts, the prevalence of refractory HTZ FH in Ontario is between 1 to 5%. Using the mean of 3%, it is estimated that there are approximately 765 refractory HTZ FH patients in Ontario, of which 115 are diagnosed and 650 are undiagnosed.
Drug therapy is less effective in HMZ FH patients since the effects of the majority of cholesterol-lowering drugs are mediated by the upregulation of LDL receptors, which are often absent or function poorly in HMZ FH patients. Some HMZ FH patients may still benefit from drug therapy, however this rarely reduces LDL-C levels to targeted levels.
Existing Technology: Plasma Exchange
An option currently available in Ontario for FH patients who do not respond to standard diet and drug therapy is plasma exchange (PE). Patients are treated with this lifelong therapy on a weekly or biweekly basis with concomitant drug therapy.
Plasma exchange is nonspecific and eliminates virtually all plasma proteins such as albumin, immunoglobulins, coagulation factors, fibrinolytic factors and HDL-C, in addition to acutely lowering LDL-C by about 50%. Blood is removed from the patient, plasma is isolated, discarded and replaced with a substitution fluid. The substitution fluid and the remaining cellular components of the blood are then returned to the patient.
The major limitation of PE is its nonspecificity. The removal of HDL-C prevents successful vascular remodeling of the areas stenosed by atherosclerosis. In addition, there is an increased susceptibility to infections, and costs are incurred by the need for replacement fluid. Adverse events can be expected to occur in 12% of procedures.
Other Alternatives
Surgical alternatives for FH patients include portocaval shunt, ileal bypass and liver transplantation. However, these are risky procedures and are associated with a high morbidity rate. Results with gene therapy are not convincing to date.
The Technology Being Reviewed: LDL Apheresis
An alternative to PE is LDL apheresis. Unlike PE, LDL apheresis is a selective treatment that removes LDL-C and other atherogenic lipoproteins from the blood while minimally impacting other plasma components such as HDL-C, total serum protein, albumin and immunoglobulins. As with PE, FH patients require lifelong therapy with LDL apheresis on a weekly/biweekly basis with concomitant drug therapy.
Heparin-Induced Extracorporeal LDL Precipitation
Heparin-induced extracorporeal LDL precipitation (HELP) is one of the most widely used methods of LDL apheresis. It is a continuous closed-loop system that processes blood extracorporeally. It operates on the principle that at a low pH, LDL and lipoprotein (a) [Lp(a)] bind to heparin and fibrinogen to form a precipitate which is then removed by filtration. In general, the total duration of treatment is approximately 2 to 3 hours.
Results from early trials indicate that LDL-C concentration is reduced by 65% to 70% immediately following treatment in both HMZ and HTZ FH and then rapidly begins to rise. Typically patients with HTZ FH are treated every 2 weeks while patients with HMZ FH require weekly therapy. Heparin-induced extracorporeal LDL precipitation also produces small transient decreases in HDL-C, however levels generally return to baseline within 2 days. After several months of therapy, long-term reductions in LDL-C and increases in HDL-C have been reported.
In addition to having an impact on plasma cholesterol concentrations, HELP lowers plasma fibrinogen, a risk factor for atherosclerosis, and reduces concentrations of cellular adhesion molecules, which play a role in early atherogenesis.
In comparison with PE, HELP LDL apheresis does not have major effects on essential plasma proteins and does not require replacement fluid, thus decreasing susceptibility to infections. One study noted that adverse events were documented in 2.9% of LDL apheresis treatments using the HELP system compared with 12% using PE. As per the manufacturer, patients must weigh at least 30kgs to be eligible for treatment with HELP.
Regulatory Status
The H.E.L.P.® System (B.Braun Medizintechnologie GmbH, Germany) has been licensed by Health Canada since December 2000 as a Class 3 medical device (Licence # 26023) for performing LDL apheresis to acutely remove LDL from the plasma of 3 high-risk patient populations for whom diet has been ineffective and maximum drug therapy has either been ineffective or not tolerated. The 3 patient groups are as follows:
Functional hypercholesterolemic homozygotes with LDL-C >500 mg/dL (>13mmol/L);
Functional hypercholesterolemic heterozygotes with LDL-C >300 mg/dL (>7.8mmol/L);
Functional hypercholesterolemic heterozygotes with LDL-C >200 mg/dL (>5.2mmol/L) and documented CAD
No other LDL apheresis system is currently licensed in Canada.
Review Strategy
The Medical Advisory Secretariat systematically reviewed the literature to assess the effectiveness and safety of LDL apheresis performed with the HELP system for the treatment of patients with refractory HMZ and HTZ FH. A standard search methodology was used to retrieve international health technology assessments and English-language journal articles from selected databases.
The GRADE approach was used to systematically and explicitly make judgments about the quality of evidence and strength of recommendations.
Summary of Findings
The search identified 398 articles published from January 1, 1998 to May 30, 2007. Eight studies met the inclusion criteria. Five case series, 2 case series nested within comparative studies, and one retrospective review, were included in the analysis. A health technology assessment conducted by the Alberta Heritage Foundation for Medical Research, and a review by the United States Food and Drug Administration were also included.
Large heterogeneity among the studies was observed. Studies varied in inclusion criteria, baseline patient characteristics and methodology.
Overall, the mean acute1 relative decrease in LDL-C with HELP LDL apheresis ranged from 53 to 77%. The mean acute relative reductions ranged as follows: total cholesterol (TC) 47 to 64%, HDL-C +0.4 to -29%, triglycerides (TG) 33 to 62%, Lp(a) 55 to 68% and fibrinogen 56 to 65%.
The mean chronic2 relative decreases in LDL-C and TC with HELP LDL apheresis ranged from 9 to 46% and 5 to 34%, respectively. Familial hypercholesterolemia patients treated with HELP did not achieve the target LDL-C value set by international guidelines (LDL-C < 2.5mmol/L, 100mg/dL). The chronic mean relative increase in HDL-C ranged from 12 to 27%. The ratio of LDL:HDL and the ratio of TC:HDL are 2 measures that have been shown to be important risk factors for cardiac events. In high-risk patients, the recommended target LDL:HDL ratio is less than or equal to 2, and the target TC:HDL ratio is less than 4. In the studies that reported chronic lipid changes, the LDL:HDL and TC:HDL ratios exceeded targeted values.
Three studies investigated the effects of HELP on coronary outcomes and atherosclerotic changes. One noted that twice as many lesions displayed regression in comparison to those displaying progression. The second study found that there was a decrease in Agatston scores3 and in the volume of coronary calcium. The last study noted that 2 of 5 patients showed regression of coronary atherosclerosis, and 3 of the 5 patients showed no change as assessed by a global change score.
Adverse effects were typically mild and transient, and the majority of events were related to problems with vascular access. Of the 3 studies that provided quantitative information, the proportion of adverse events ranged from 2.9 to 5.1%.
GRADE Quality of Evidence
In general, studies were of low quality, i.e., case series studies (Tables 1-3). No controlled studies were identified and no studies directly compared the effectiveness of the HELP system with PE or with diet and drug therapy. Conducting trials with a sufficiently large control group would not have been feasible or acceptable given that HELP represents a last alternative in these patients who are resistant to conventional therapeutic strategies.
A major limitation is that there is limited evidence on the effectiveness and safety of HELP apheresis in HMZ FH patients. However, it is unlikely that better-quality evidence will become available, given that HMZ FH is rare and LDL apheresis is a last therapeutic option for these patients.
Lastly, there is limited data on the long-term effects of LDL apheresis in FH patients. No studies with HELP were identified that examined long-term outcomes such as survival and cardiovascular events. The absence of this data may be attributed to the rarity of the condition, and the large number of subjects and long duration of follow-up that would be needed to conduct such trials.
Homozygous Familial Hypercholesterolemia - Lipid Outcomes
Heterozygous Familial Hypercholesterolemia - Lipid Outcomes
Heterozygous Familial Hypercholesterolemia - Coronary Artery Disease Outcomes
Economic Analysis
A budget-impact analysis was conducted to forecast future costs for PE and HELP apheresis in FH patients. All costs are reported in Canadian dollars. Based on epidemiological data of 13 HMZ, 115 diagnosed HTZ and 765 cases of all HTZ patients (diagnosed + undiagnosed), the annual cost of weekly treatment was estimated to be $488,025, $4,332,227 and $24,758,556 respectively for PE. For HELP apheresis, the annual cost of weekly treatment was estimated to be $1,025,338, $9,156,209 and $60,982,579 respectively. Costs for PE and HELP apheresis were halved with a biweekly treatment schedule.
The cost per coronary artery disease death avoided over a 10-year period in HTZ FH-diagnosed patients was also calculated and estimated to be $37.5 million and $18.7 million for weekly and biweekly treatment respectively, when comparing HELP apheresis with PE and with no intervention. Although HELP apheresis costs twice as much as PE, it helped to avoid 12 deaths compared with PE and 22 deaths compared with no intervention, over a period of 10 years.
Ontario Health System Impact Analysis
Low-density lipoprotein apheresis using the HELP system is currently being funded by the provinces of Quebec and Alberta. The program in Quebec has been in operation since 2001 and is limited to the treatment of HMZ FH patients. The Alberta program is relatively new and is currently treating HMZ FH patients, but it is expanding to include refractory HTZ FH patients.
Low-density lipoprotein apheresis is a lifelong treatment and requires considerable commitment on the part of the patient, and the patient’s family and physician. In addition, the management of FH continues to evolve. With the advent of new more powerful cholesterol-lowering drugs, some HTZ patients may be able to sufficiently control their hypercholesterolemia. Nevertheless, according to clinical experts, HMZ patients will likely always require LDL apheresis.
Given the substantial costs associated with LDL apheresis, treatment has been limited to HMZ FH patients. However, LDL apheresis could be applied to a much larger population, which would include HTZ FH patients who are refractory to diet and drug therapy. HTZ FH patients are generally recruited in a more advanced state, demonstrate a longer natural survival than HMZ FH patients and are older.
Conclusions
For HMZ FH patients, the benefits of LDL apheresis clearly outweigh the risks and burdens. According to GRADE, the recommendation would be graded as strong, with low- to very low-quality evidence (Table 4).
In both HMZ and HTZ FH patients, there is evidence of overall clinical benefit of LDL apheresis from case series studies. Low-density lipoprotein apheresis has several advantages over the current treatment of PE, including decreased exposure to blood products, decreased risk of adverse events, conservation of nonatherogenic and athero-protective components, such as HDL-C and lowering of other atherogenic components, such as fibrinogen.
In contrast to HMZ FH patients, there remains a lot of uncertainty in the social/ethical acceptance of this technology for the treatment of refractory HTZ FH patients. In addition to the substantial costs, it is unknown whether the current health care system could cope with the additional demand. There is uncertainty in the estimates of benefits, risks and burdens. According to GRADE, the recommendation would be graded as weak with low- to very-low-quality evidence (Table 5).
GRADE Recommendation - Homozygous Patients
GRADE of recommendation: Strong recommendation, low-quality or very-low-quality evidence
Benefits clearly outweigh risk and burdens
Case series study designs
Strong, but may change when higher-quality evidence becomes available
GRADE Recommendation - Heterozygous Patients
GRADE of recommendation: Weak recommendation, low-quality or very-low-quality evidence
Uncertainty in the estimates of benefits, risks and burden, which these may be closely balanced
Case series study designs
Very weak; other alternatives may be equally reasonable
PMCID: PMC3377562  PMID: 23074505
2.  Gilbert's syndrome in healthy blood donors what next?? 
Settings:
This study was done in a tertiary care hospital having bed strength of more than 700 beds at SDM Medical College of Medical Sciences and Hospital, Dharwad, located in Northern Karnataka.
Aim:
The study was done to ascertain prevalence of Gilbert's syndrome in healthy blood donors and review the literature about feasibility of utilizing blood components from Gilbert's syndrome donors.
Materials and Methods:
The study was done for 18 months and 7030 whole blood units were collected and all the units were subjected to mandatory transfusion-transmitted screening and all the plasma bags which were icteric on visual inspection were subjected to hematological and biochemical investigations to rule out other causes of hyperbilirubinemia.
Results:
Seven thousand and thirty units were collected and 445 (6.3%) were discarded due to various reasons. Of them, 50 units (0.71%) had Gilbert's syndrome. All had unconjugated hyperbilirubinemia and other hematological and liver function tests were within normal range. Statistical analysis was done to find mean, median, and standard deviation from mean and standard error of mean with lower and upper confidence limits.
Conclusion:
Majority of blood donors whose plasma is icteric are suffering from Gilbert's syndrome (GS). This disease does not cause any harm to donor or patient but raises a lot of concern as many severe disorders also manifest in similar way. The available literature shows that all blood components can be used from donors suffering from GS. There should be introspection. Proper guidelines are to be framed about the use and discarding of blood components in donors with GS.
doi:10.4103/0973-6247.165835
PMCID: PMC4782497  PMID: 27011673
Blood safety; fresh frozen plasma; Gilbert's syndrome; hyperbilirubinemia; jaundice
3.  Demographic Characteristics and Prevalence of Serologic Markers among Blood Donors Who Use Confidential Unit Exclusion (CUE) in São Paulo, Brazil: Implications for Modification of CUE Polices in Brazil 
Transfusion  2011;51(1):191-197.
Background
This study evaluated demographic profiles and prevalence of serologic markers of donors who used CUE in order to assess the effectiveness of CUE and guide public policies regarding the use of CUE for enhancing safety versus jeopardizing the blood supply by dropping CUE.
Material and Methods
We conducted a cross-sectional analysis of whole blood donations at a large public blood center in São Paulo from July 2007 through June 2009, and compared demographic data and confirmed serologic results among donors who used and who have never used CUE (CUE never).
Results
There were 265,550 whole blood units collected from 181,418 donors from July 2007 through June 2009. A total of 9,659 (3.6%) units were discarded, 2,973 (1.1%) because CUE was used at the current donation (CUE now) and 6,685 (2.5%) because CUE was used in the past (CUE past). The CUE rate was highest among donors with less than 8 years of education (OR=2.78; CI = 2.51–3.08). CUE now donations were associated with higher positive infectious disease marker rates than CUE never donations (OR= 1.41; CI = 1.13–1.77), whereas CUE past donations were not (OR=1.04; CI = 0.75–1.45).
Conclusion
The CUE process results in a high rate of unit discard. CUE use on an individual donation appears predictive of a high risk marker positive donation and, thus appears to contribute modestly to blood safety. The policy of discarding units from donors, who have previously CUE positive donations, does not improve safety and should be discontinued.
doi:10.1111/j.1537-2995.2010.02799.x
PMCID: PMC3170091  PMID: 20663108
HIV; blood donors; Brazil; donor selection; risk reduction behavior
4.  Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure 
Transfusion  2010;51(6):1197-1206.
BACKGROUND
Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States.
STUDY DESIGN AND METHODS
We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type.
RESULTS
A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively.
CONCLUSION
A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.
doi:10.1111/j.1537-2995.2010.02991.x
PMCID: PMC3606016  PMID: 21182532
5.  Erythrocyte Concentrates Recovered from Under-Collected Whole Blood: Experimental and Clinical Results 
PLoS ONE  2015;10(2):e0117928.
Background
Although periodic blood shortages are widespread in major Chinese cities, approximately 1x105 U of whole blood are discarded yearly because of under-collection. To reduce the wastage of acid citrate dextrose solution B (ACD-B) anticoagulated under-collected whole blood (UC-WB), this study was performed to elucidate the effect of extracellular pH and holding time on erythrocyte quality. Mannitol-adenine-phosphate (MAP) erythrocyte concentrates (UC-RBCs) were prepared with UC-WB to assess the safety and efficacy of this component.
Methods
The effect of the different extracellular pH levels and storage times on erythrocytes was assessed by fluorescent probes, SDS-PAGE electrophoresis, electron microscopy and spectroscopy. In vitro properties of 34 UC-RBCs that were prepared with UC-WB at different times after collection were analyzed and compared to normal RBCs during 35 days of storage. The results of transfusion with UC-RBCs and the incidence of adverse reactions in 49 patients were determined.
Results
1) Low extracellular pH levels and long storage time induced increases in RBC fluorescence polarization and mean microviscosity, changes in membrane fluidity, band 1, 2 and 3 protein expression, and erythrocyte morphology. 2) During storage for 35 days, difference in between-subjects effects of K+, hemolysis and supernatant erythrocyte membrane protein (EMP) were statistically significant (P = 0.041, 0.007 and 0.002, respectively), while the differences between these parameters in the 4 h group and comparable controls were less significant. 3) Clinical data from 49 patients confirmed that transfusions with UC-RBCs were satisfactory with no adverse reactions.
Conclusion
These results suggest that it is feasible to prepare RBCs with ACD-B anticoagulated UC-WB at a minimum of 66% volume of the labeled collection. It was effective and safe to transfuse the UC-RBCs prepared within 4 h after collection and stored within 7 days. The use of UC-WB would be a welcome addition to limited blood resources in China.
Trial Registration
Chinese Clinical Trial Registry ChiCTR-TRC-13003967
doi:10.1371/journal.pone.0117928
PMCID: PMC4338272  PMID: 25706725
6.  Namibia’s transition from whole blood–derived pooled platelets to single-donor apheresis platelet collections 
Transfusion  2015;55(7):1685-1692.
BACKGROUND
Few African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT availability while reducing exposure to multiple donors via pooling. This study describes the impact this transition had on PLT availability and safety in Namibia.
STUDY DESIGN AND METHODS
Annual national blood collections and PLT units issued data were extracted from a database maintained by the Blood Transfusion Service of Namibia (NAMBTS). Production costs and unit prices were analyzed.
RESULTS
In 2006, NAMBTS issued 771 single and pooled PLT doses from 3054 whole blood (WB) donations (drawn from 18,422 WB donations). In 2007, NAMBTS issued 486 single and pooled PLT doses from 1477 WB donations (drawn from 18,309 WB donations) and 131 single-donor PLT doses. By 2011, NAMBTS issued 837 single-donor PLT doses per year, 99.1% of all PLT units. Of 5761 WB donations from which PLTs were made in 2006 to 2011, a total of 20 (0.35%) were from donors with confirmed test results for human immunodeficiency virus or other transfusion-transmissible infections (TTIs). Of 2315 single-donor apheresis donations between 2007 and 2011, none of the 663 donors had a confirmed positive result for any pathogen. As apheresis replaced WB-derived PLTs, apheresis production costs dropped by a mean of 8.2% per year, while pooled PLT costs increased by an annual mean of 21.5%. Unit prices paid for apheresis- and WB-derived PLTs increased by 9 and 7.4% per year on average, respectively.
CONCLUSION
Namibia’s PLT transition shows that collections from repeat apheresis donors can reduce TTI risk and production costs.
doi:10.1111/trf.13049
PMCID: PMC4607307  PMID: 25727921
7.  Utilisation of Blood Components in Trauma Surgery: A Single-Centre, Retrospective Analysis before and after the Implementation of an Educative PBM Initiative 
Background
The aim of our single-centre retrospective study presented here is to further analyse the utilisation of allogeneic blood components within a 5-year observation period (2009-2013) in trauma surgery (15,457 patients) under the measures of an educational patient blood management (PBM) initiative.
Methods
After the implementation of the PBM initiative in January 2012, the Institute of Transfusion Medicine und Transplantation Immunology educates surgeons and nurses at the Department of Trauma Surgery to avoid unnecessary blood transfusions. A standardised reporting system was used to document the utilisation of blood components carefully for the most frequent diagnoses and surgical interventions in trauma surgery. These measures served as basis for the implementation of an interdisciplinary systematic exchange of information to foster decision-making processes in favour of patient blood management.
Results
Since January 2012, the proportion of patients who received a transfusion as well as the number of transfused red blood cell (RBC) (7.3%/6.4%; p = 0.02), fresh frozen plasma (FFP) (1.7%/1.3%; p < 0.05) and platelet (PLT) (1.0%/0.5%; p < 0.001) units were reduced as a result of our PBM initiative. However, among the transfused patients, the number of administered RBC, FFP and PLT units did not decrease significantly. Overall, patients who did not receive transfusions were younger than transfused patients (p = 0.001). The subgroup with the highest probability of blood transfusion administered included patients with intensive care and long-term ventilation (before/after implementation of PBM: RBC 81.5%/75.9%; FFP 33.3%/20.4%; PLT 24.1%/13.0%). Only a total of 60 patients of 531 patients suffering multiple traumas were massively transfused (before/after implementation of PBM: RBC 55.6%/49.8%; FFP 28.4%/20.4%; PLT 17.6%/8.9%).
Conclusion
According to our educational PBM initiative, at least the proportion of trauma patients who received allogeneic blood transfusions could be reduced significantly. However, in case of blood transfusions, the total consumption of RBC, FFP and PLT units remained stable in both time periods. This phenomenon might indicate that the actual need of blood transfusions rather depends on the severity of trauma-related blood loss, the coagulopathy rates or the complexity of the surgical intervention which mainly determines the intra-operative blood loss. Taken together, educational training sessions and systematic reporting systems are suitable measures to avoid unnecessary allogeneic blood transfusions and to continuously improve their restrictive application.
doi:10.1159/000377735
PMCID: PMC4439836  PMID: 26019703
Trauma surgery; Patient blood management; Blood supply; Haemotherapy; Health services research
8.  Four phases of checks for exclusion of umbilical cord blood donors 
Blood Transfusion  2011;9(3):286-291.
Aim
The aim of this study was to analyse umbilical cord blood (UCB) collection over 1 year between October 2008 and September 2009, seeking ways to improve the number of suitable banked UCB units. Four phases of the process were investigated, from the consent form to the banking procedure, paying attention to the discarded UCB units.
Material and methods
We recruited couples at 35 weeks of gestation and took an accurate history, focusing on genetic, immunological and infectious diseases. We collected UCB from pregnant women who delivered vaginally or by Caesarean section between the 37–41+6 weeks of gestation. Some units were discarded on the basis of the patients' history, obstetric events or biological criteria. In utero collection was the preferred method of collection.
Results
During the study period, between October 2008 and September 2009, there were 1,477 deliveries in our unit. The number of couples interested in UCB donation was 595 (40.2%-595/1,477). We collected 393 UBC units. We excluded 122 patients at the phase of the history taking, counselling and informed consent (first phase check). Of the 393 units collected, 162 (41.3%) were banked whereas 231 (58.7%) were discarded because they did not fulfil biological criteria (third phase check). The volume of UCB units collected after Caesarean section was greater than the volume of units collected after vaginal delivery (95.4 mL versus 85.0 mL, respectively; p <0.01). The UCB units collected after vaginal delivery contained a higher number of total nucleated cells compared to the units collected after Caesarean section (970x106 cells versus 874x106 cells, respectively; p=0.037). None of the banked UCB units was discarded at the clinical check 6 months after delivery (fourth phase check).
Conclusions
Our study shows that strict observance of each of the checks and the collection strategy is important to guarantee the safety of the UCB units and to maximise the cost-benefit ratio. After the appropriate checks we banked UCB units from only 27.2% (162/595) of the couples who gave consent to the procedure and from only 11% (162/1,477) of all the deliveries in the 12 month study period, as 59.8% of couples were not properly informed about UCB donation.
doi:10.2450/2011.0038-10
PMCID: PMC3136596  PMID: 21627927
cord blood; obstetric factors; stem cells
9.  Cost effectiveness of Iran national plasma contract fractionation program 
Plasma derived medicines (PDM) including immunoglobulins, clotting factors and albumin are life saving medicines which due to their high costs are inaccessible for many patients living in developing countries. By contrary substantial volume of plasma as raw materials for production of these medicines are discarded worldwide. Good quality recovered plasma, as a result of separation of donated blood into its components, could be used for production of PDM. In 2011 Iranian donors donated about 2 million units of blood. A shift from administration of whole blood to components therapy has resulted in the generation of over 250,000 liters of surplus of recovered plasma. This created a good opportunity for Iran’s health care system to use this plasma for production of PDM. Therefore Iran national transfusion service has started a contract fractionation program for converting recovered plasma into PDM. This program not only provided essential PDM for Iran pharmaceutical market but also has created a direct saving of about 8.5 million Euros in 2011 for national health sector. In addition this program has drastically contributed to improvement of overall quality of working procedures and services provided by Iran national blood transfusion organization.
doi:10.1186/2008-2231-20-63
PMCID: PMC3556006  PMID: 23351278
Iran; Cost effectiveness; Plasma contract fractionation; Blood transfusion service
10.  Evaluation of DNA extraction from granulocytes discarded in the separation medium after isolation of peripheral blood mononuclear cells and plasma from whole blood 
BMC Research Notes  2013;6:440.
Background
Whole blood is generally processed for plasma and peripheral blood mononuclear cells (PBMCs) from granulocytes/erythrocytes using gradient centrifugation of blood with Histopaue-Ficoll. After separation of plasma and PBMCs, the residual erythrocytes/granulocytes, a rich source of DNA, is often discarded along with the separation medium. In order to isolate DNA from the granulocytes, current methods require the removal of the separation medium and subsequent purification of granulocytes. This report provides a method for extracting DNA using the PAXgene Blood DNA kit from granulocytes without purifying them from the separation medium.
Findings
Based on 719 erythrocyte/granulocyte samples stored frozen for approximately 10 years in Ficoll-Hypaque separation medium, the mean yield of DNA was 395 μg (median = 281 μg; range = 1.36 to 2077.2 μg), with mean A260/A280 ratio of 1.84 (median = 1.84; range = 1.17 to 2.23). The quality of isolated DNA was sufficient for use as a template for restriction enzyme digestion, real-time PCR, pyrosequencing, and gel based variable number tandem repeats (VNTR) genotyping.
Conclusions
By demonstrating the extraction of substantial amounts of high quality granulocytes DNA without purifying them from the separation medium, this method offers laboratories and biobanks a flexible and cost-effective approach to obtain plasma, PBMCs, and large amounts of DNA from a single blood collection for a variety of molecular genetics/epidemiologic studies.
doi:10.1186/1756-0500-6-440
PMCID: PMC3818442  PMID: 24176175
DNA extraction; Granulocytes in separation medium; Whole blood
11.  Gravity sedimentation of granulocytapheresis concentrates with hydroxyethyl starch efficiently removes red blood cells and retains neutrophils 
Transfusion  2010;50(6):1203-1209.
BACKGROUND
Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC-incompatible units.
STUDY DESIGN AND METHODS
Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte–colony-stimulating factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined.
RESULTS
Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150–440 min). RBC depletion was 92% (range, 71%–99%) with mean residual RBC content of 3.2 ± 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.6–8.2 mL). The remaining concentrates were used for topical or intrapleural applications.
CONCLUSIONS
RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/ steroid–mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.
doi:10.1111/j.1537-2995.2009.02576.x
PMCID: PMC3421031  PMID: 20113453
12.  Acute Free-Iron Exposure Does Not Explain the Impaired Haemorheology Associated with Haemochromatosis 
PLoS ONE  2016;11(1):e0146448.
Introduction
Given the severity of the current imbalance between blood donor supply and recipient demand, discarded blood drawn from the routine venesections of haemochromatosis (HFE-HH) patients may serve as a valuable alternative source for blood banks and transfusion. We investigated whether functional or biochemical differences existed between HFE-HH and control blood samples, with particular focus upon the haemorheological properties, to investigate the viability of venesected blood being subsequently harvested for blood products.
Methods
Blood samples were collected from HFE-HH patients undergoing venesection treatment (n = 19) and healthy volunteers (n = 8). Moreover, a second experiment investigated the effects of a dose-response of iron (0, 40, 80, 320 mM FeCl3) on haemorheology in healthy blood samples (n = 7). Dependent variables included basic haematology, iron status, haematocrit, red blood cell (RBC) aggregation (native and standardised haematocrit) and “aggregability” (RBC tendency to aggregate in a standard aggregating medium; 0.4 L/L haematocrit in a Dx70), and RBC deformability.
Results
Indices of RBC deformability were significantly decreased for HFE-HH when compared with healthy controls: RBC deformability was significantly decreased at 1–7 Pa (p < 0.05), and the shear stress required for half maximal deformability was significantly increased (p < 0.05) for HFE-HH. RBC aggregation in plasma was significantly increased (p < 0.001) for HFE-HH, although when RBC were suspended in plasma-free Dx70 no differences were detected. No differences in RBC deformability or RBC aggregation/aggregability were detected when healthy RBC were incubated with varying dose of FeCl3.
Conclusion
HFE-HH impairs the haemorheological properties of blood; however, RBC aggregability was similar between HFE-HH and controls when cells were suspended in a plasma-free medium, indicating that plasma factor(s) may explain the altered haemorheology in HFE-HH patients. Acute exposure to elevated iron levels does not appear (in isolation) to account for these differences. Further consideration is required prior to utilising routine venesection blood for harvesting RBC concentrates due to the potential risk of microvascular disorders arising from impaired haemorheology.
doi:10.1371/journal.pone.0146448
PMCID: PMC4712145  PMID: 26741993
13.  Effects of group culture on the development of discarded human embryos and the construction of human embryonic stem cell lines 
Purpose
To explore the effect of group culture on the developmental potential of discarded embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles and establish the human embryonic stem cell lines for future research.
Methords
Fresh discarded embryos were collected from the IVF/ICSI-ET program in the reproductive medical center of the first affiliated hospital of Zhengzhou university in this study. All zygotes were individually cultured from Day 1 to Day 3. On Day 3, discard embryos were then cultured in group of 1–4 embryos per droplet (30 μl/droplets) with a constant culture medium until Day 5 or 6. Mechanical method was used to isolate the inner cell mass (ICM) of blastocyst from the embryo. Then we inoculated the ICM on feeder layer. After identification of those cells, the human embryonic stem cell lines (hESCs) were established.
Results
In this study, we collected 1,223 fresh discarded embryos and they were sequential cultured to the blastocysts (18.07 %, 221/1,223), in which good quality blastocysts were 61(4.98 %, 61/1,223). There was no significant difference in the patients. The embryos from 1PN, 2PN, 3PN were sequential cultured to the blastocyst s(39.31 %,92/234;12.87 %,64/497;13.21 %,65/492),in which good quality blastocysts was 13.6 %(32/92),2.61 %(13/64), 3.04 %(15/65).1PN embryo’s blastulation rate and quality embryo formation rate was significantly higher than the 2PN and 3PN embryos’ (P <0.05). Three embryos group cultivation has the highest blastulation rate and quality embryo formation rate (P <0.05). In total, we successfully established 4 hESCs lines.
Conclusion
The group culture of human discard embryos can improve the blastulation rate and blastocyst quality to some extent. Three embryos group cultivate is the better culture number. Human discard embryos are good source for establishment of hESCs.
doi:10.1007/s10815-014-0308-y
PMCID: PMC4171410  PMID: 25113620
Group culture; Human discard embryo; Blastocyst; Human embryonic stem cell
14.  Effectiveness of confidential unit exclusion in screening blood donors of the regional blood bank in Londrina, Paraná State 
Background
For transfusion purposes, blood donors must be accepted both in clinical and serological evaluations and must not have excluded their own donation using the confidential unit exclusion.
Aim
The objective of this study was to verify whether blood donors who choose self exclusion are more likely to be positive in serological tests than donors who do not.
Methods
A cross-sectional analysis was carried out of 51,861 consecutive whole blood donations from January 2004 to December 2008 at a public blood bank in Londrina, Southern Brazil.
Results
Self exclusion was chosen in 1672 (3.2%) donations, most frequently by first-time blood donors (p-value < 0.0001), by blood donors from external collections (p-value < 0.0001), by men (p value < 0.0001) and by under 30-year-old donors (p-value < 0.0001). The frequency of positive serology was 5.3% in the group that chose self exclusion and 3.5% in the group that did not choose self exclusion (p-value < 0.0001).
Conclusions
These results show that confidential unit exclusion used in this blood bank is effective and is inexpensive. However, the diagnostic power to detect blood-borne infections was low and resulted in the discard of a high number of blood bags without any direct or indirect serologic markers of pathogens. The use of confidential unit exclusion could be replaced with molecular tests to screen blood donors.
doi:10.5581/1516-8484.20110097
PMCID: PMC3415772  PMID: 23049338
Donor selection; Serologic tests; Diagnosis; Blood transfusion
15.  What happens to donated blood? 
Pursuing their chief work--gathering, processing and distributing blood--the blood donor centres of the Canadian Red Cross Society follow standard operating procedures like those in place at the Ottawa centre. Here, recruitment staff and volunteers work to recruit donors to meet needs at a time when the number of donors is falling. When they register, donors must show proof of identity. Each receives a permanent identification number that is linked to the numbers assigned to the units of blood each donates and to the date the unit was collected and the centre that collected it. Donors must answer questions about health and high-risk activity, and the blood of those who report high-risk activity is not accepted. Units are screened by automated instruments for syphilis, hepatitis B and C, HIV types 1 and 2, and human T-cell leukemia virus. Units with a negative test result are broken down into components for use in hospitals. A reactive test result prompts quarantining of the unit and a second screening test. If this test result is also reactive, a sample of the unit is sent to the National Testing Laboratory for confirmatory testing, and the unit is discarded. Once it has the results of the confirmatory test, the centre contacts the donor. Blood is now considered a drug. Red Cross practices in Canada and around the world have been changing since 1989 to reflect this.
Images
PMCID: PMC1337706  PMID: 7859200
16.  Quality of Red Blood Cells Isolated from Umbilical Cord Blood Stored at Room Temperature 
Journal of blood transfusion  2011;2012:102809.
Red blood cells (RBCs) from cord blood contain fetal hemoglobin that is predominant in newborns and, therefore, may be more appropriate for neonatal transfusions than currently transfused adult RBCs. Post-collection, cord blood can be stored at room temperature for several days before it is processed for stem cells isolation, with little known about how these conditions affect currently discarded RBCs. The present study examined the effect of the duration cord blood spent at room temperature and other cord blood characteristics on cord RBC quality. RBCs were tested immediately after their isolation from cord blood using a broad panel of quality assays. No significant decrease in cord RBC quality was observed during the first 65 hours of storage at room temperature. The ratio of cord blood to anticoagulant was associated with RBC quality and needs to be optimized in future. This knowledge will assist in future development of cord RBC transfusion product.
doi:10.1155/2012/102809
PMCID: PMC3777252  PMID: 24089645
17.  Stored Platelet Functionality is Not Decreased After Warming with a Fluid Warmer 
Anesthesia and analgesia  2013;117(3):575-578.
Background
Warming of IV administered fluids and blood products is routinely performed in the operating room to help maintain normothermia. Current guidelines recommend against the warming of platelets (PLTs), although there is no evidence for this prohibition in the literature. Our goal in this pilot study was to determine if the warming of stored PLTs had any effect on their function.
Methods
Ten units of three-day-old PLT rich plasma-derived whole blood PLTs were acquired from the transfusion service. A 5 mL aliquot was taken from each unit before warming (control samples). The remainder of the unit was then passed into a blood warming device and held there for two minutes. Post-warming (warmed) PLT samples were then collected from the effluent end of the warming device. PLT aggregometry assays with adenosine diphosphate, collagen, and arachidonic acid as agonists were performed on the control and warmed samples. Thromboelastrography (TEG®) tests were also performed on the control and warmed samples from six of the 10 PLT units.
Results
The mean temperature of the control and warmed samples was 22.4 ± 0.5°C and 37.8 ± 2.3°C, respectively. There was no significant difference (all P ≥ 0.13) in any of the PLT aggregometry assays or in the maximum amplitude of the TEG® test between the control and the warmed samples. The observed mean of only one parameter decreased (PLT aggregometry with 5 µM adenosine diphosphate), by 5% (95% CI: −115% to 105%). The maximum change observed was PLT aggregometry with arachidonic acid as agonist, which increased by 116% (95% CI: −91% to 323%).
Conclusion
Although small in size, the results of this study do not support the prohibition against mechanical PLT warming. Studies of PLT activation after warming are also warranted.
doi:10.1213/ANE.0b013e31829cfdfa
PMCID: PMC3784352  PMID: 23921655
18.  Quality Improvement Methodologies Increase Autologous Blood Product Administration 
Abstract:
Whole blood from the heart–lung (bypass) machine may be processed through a cell salvaging device (i.e., cell saver [CS]) and subsequently administered to the patient during cardiac surgery. It was determined at our institution that CS volume was being discarded. A multidisciplinary team consisting of anesthesiologists, perfusionists, intensive care physicians, quality improvement (QI) professionals, and bedside nurses met to determine the challenges surrounding autologous blood delivery in its entirety. A review of cardiac surgery patients’ charts (n = 21) was conducted for analysis of CS waste. After identification of practices that were leading to CS waste, interventions were designed and implemented. Fishbone diagram, key driver diagram, Plan–Do–Study–Act (PDSA) cycles, and data collection forms were used throughout this QI process to track and guide progress regarding CS waste. Of patients under 6 kg (n = 5), 80% had wasted CS blood before interventions, whereas those patients larger than 36 kg (n = 8) had 25% wasted CS before interventions. Seventy-five percent of patients under 6 kg who had wasted CS blood received packed red blood cell transfusions in the cardiothoracic intensive care unit within 24 hours of their operation. After data collection and didactic education sessions (PDSA Cycle I), CS blood volume waste was reduced to 5% in all patients. Identification and analysis of the root cause followed by implementation of education, training, and management of change (PDSA Cycle II) resulted in successful use of 100% of all CS blood volume.
PMCID: PMC4557510  PMID: 24783313
autologous blood; cell saver; quality improvement; Plan–Do–Study–Act; fishbone; key driver diagram; multidisciplinary team; cardiopulmonary bypass; continuous quality improvement; cell saver waste; pediatric
19.  Anti-HBc screening in Indian blood donors: Still an unresolved issue 
AIM: To study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in India as a screening assay for HBV in addition to HBsAg.
METHODS: A total of 1700 serum samples collected from HBsAg-negative healthy blood donors were tested for the presence of anti-HBc antibody (IgM + IgG). All samples reactive for anti-HBc antibody were then investigated for presence of anti-HBs and for liver function tests (LFTs). One hundred serum samples reactive for anti-HBc were tested for HBV DNA by PCR method.
RESULTS: Out of 1700 samples tested, 142 (8.4%) blood samples were found to be reactive for anti-HBc. It was significantly lower in voluntary (6.9%) as compared to replacement donors (10.4%, P = 0.011). Seventy-two (50.7%) anti-HBc reactive samples were also reactive for anti-HBs with levels > 10 mIU/mL and 70 (49.3%) samples were non-reactive for anti-HBs, these units were labeled as anti-HBc-only. These 142 anti-HBc reactive units were also tested for liver function test. HBV DNA was detected in only 1 of 100 samples tested.
CONCLUSION: Keeping in view that 8%-18% of donor population in India is anti-HBc reactive, inclusion of anti-HBc testing will lead to high discard rate. Anti-HBs as proposed previously does not seem to predict clearance of the virus. Cost effectiveness of introducing universal anti-HBc screening and discarding large number of blood units versus considering ID NAT (Individual donor nuclic acid testing) needs to be assessed.
doi:10.3748/wjg.14.5327
PMCID: PMC2744065  PMID: 18785287
Hepatitis B core antigen; Hepatitis B surface antigen; Hepatitis B virus; Transfusion-associated hepatitis B virus; Blood donors
20.  Frequency and Pattern of Noninfectious Adverse Transfusion Reactions at a Tertiary Care Hospital in Korea 
Annals of Laboratory Medicine  2015;36(1):36-41.
Background
Although transfusion is a paramount life-saving therapy, there are multiple potential significant risks. Therefore, all adverse transfusion reaction (ATR) episodes require close monitoring. Using the computerized reporting system, we assessed the frequency and pattern of non-infectious ATRs.
Methods
We analyzed two-year transfusion data from electronic medical records retrospectively. From March 2013 to February 2015, 364,569 units of blood were transfused. Of them, 334,582 (91.8%) records were identified from electronic nursing records. For the confirmation of ATRs by blood bank physicians, patients' electronic medical records were further evaluated.
Results
According to the nursing records, the frequency of all possible transfusion-related events was 3.1%. After the blood bank physicians' review, the frequency was found to be 1.2%. The overall frequency of febrile non-hemolytic transfusion reactions (FNHTRs) to red blood cells (RBCs), platelet (PLT) components, and fresh frozen plasmas (FFPs) were 0.9%, 0.3%, and 0.2%, respectively, and allergic reactions represented 0.3% (RBCs), 0.9% (PLTs), and 0.9% (FFPs), respectively. The pre-storage leukocyte reduction significantly decreased the frequency of FNHTRs during the transfusion of RBCs (P<0.01) or PLTs (P≒0.01).
Conclusions
The frequency of FNHTRs, allergic reactions, and "no reactions" were 22.0%, 17.0%, and 60.7%, respectively. Leukocyte-reduction was associated with a lower rate of FNHTRs, but not with that of allergic reactions. The development of an effective electronic reporting system of ATRs is important in quantifying transfusion-related adverse events. This type of reporting system can also accurately identify the underlying problems and risk factors to further the quality of transfusion care for patients.
doi:10.3343/alm.2016.36.1.36
PMCID: PMC4697341  PMID: 26522757
Adverse transfusion reaction; Febrile non-hemolytic transfusion reaction; Allergic reaction; Transfusion reporting system
21.  Freezer anthropology: new uses for old blood. 
Archived blood fractions (plasma, settled red cells, white cells) have proved to be a rich and valuable source of DNA for human genetic studies. Large numbers of such samples were collected between 1960 and the present for protein and blood group studies, many of which are languishing in freezers or have already been discarded. More are discarded each year because the usefulness of these samples is not widely understood. Data from DNA derived from 10-35-year-old blood samples have been used to address the peopling of the New World and of the Pacific. Mitochondrial DNA haplotypes from studies using this source DNA support a single wave of migration into the New World (or a single source population for the New World), and that Mongolia was the likely source of the founding population. Data from Melanesia have shown that Polynesians are recent immigrants into the Pacific and did not arise from Melanesia.
PMCID: PMC1692452  PMID: 10091252
22.  Report on Notifications Pursuant to §21 German Transfusion Act for 2007 
Summary
The present report contains the data collected in 2007, pursuant to Section 21 German Transfusion Act, and an analysis of the supply situation over the past 8 years. As in previous years, all blood donation centres located in Germany transmitted data on the collection, manufacture, import and export of blood components for transfusion. According to these data, a total of 6.7 million blood collections were performed in 2007. With 4.7 million, the portion of whole blood donations was at the level of previous years, whereas the number of apheresis donations rose again, to 1.9 million. The portion of autologous blood collections accounts for only 1.1% and thus continues to decline. Since 2003, the number of red blood cell concentrates prepared has been a constant 4.5 million transfusion units. The decay of red blood cell concentrates on the user side in 2000 accounted for 5% while in 2007 it was just above 3%, referred to the total quantity of data reported as transfused and decayed. The manufacture of platelet concentrates rose from 366,000 to 480,000 transfusion units between 2003 and 2007. The production of therapeutic single plasmas, too, markedly increased in 2007 (to 1.2 million transfusion units). In 2007, 2.2 million I of plasma for fractionation were collected in Germany. In addition, 1.0 million I were imported, and 1.8 million I were exported. The quantity available in Germany from a pure arithmetic point of view of 1.4 million I was almost entirely allocated to basic fractionation so that a sufficient plasma supply can be assumed. Due to the fact that manufacturing capacities are still lacking in Germany, recombinant factors need to be imported in their entirety. Since 2003, Germany has by far been the leader in Europe with more than 20 I of fractionation plasma collected per 1,000 inhabitants. Furthermore, regarding the manufacturing figures of red blood cell concentrates, platelet concentrates, and therapeutic single plasma, Germany is in the top third for all these products compared with other European countries. The manufacture of allogeneic stem cell products for haematopoietic reconstitution, obtained by apheresis, has continuously risen to 4,700. A large portion of this (1,810 transplants) could be exported while only a small number (179 preparations) had to be imported. The manufacture of autologous stem cell preparations from cord blood has risen drastically to more than 10,000 in 2007. The interest in the figures collected in compliance with Section 21, German Transfusion Act remains high both in Germany and at an international level. Meanwhile reliable data are available.
doi:10.1159/000269555
PMCID: PMC2914406  PMID: 20737014
Blood donations; Erythrocyte concentrates; Plasma for fractionation; Blood coagulation factors; Supply situation
23.  Changing the 30-min Rule in Canada: The Effect of Room Temperature on Bacterial Growth in Red Blood Cells 
Background
To maintain product quality and safety, the ‘30-min rule’ requires the discard of red blood cells (RBCs) that are exposed to uncontrolled temperatures for more than 30 min. Recent studies suggest this rule may safely be extended to a 60-min rule.
Methods
A pool-and-split design study (N = 4) was run in parallel at Canadian Blood Services (SAGM RBCs) and Héma-Québec (AS-3 RBCs). RBCs were spiked with ∼1 colony-forming unit/ml of mesophilic and psychrophilic bacteria. Control units remained in storage at 1-6 °C for 42 days. Test 30 (T30) and T60 units were exposed to room temperature (RT) six times during storage, each time for 30 and 60 min, respectively. Bacterial proliferation was monitored.
Results
Mesophilic bacteria do not proliferate in RBCs. The growth of psychrophilic bacteria is not significantly different in RBCs exposed for 30 or 60 min to RT (p < 0.05).
Conclusion
The study findings were the final evidence to support extension from a 30-min rule to a 60-min rule in Canada.
doi:10.1159/000445753
PMCID: PMC5159731  PMID: 27994525
30-min rule; Red blood cells; Bacteria
24.  Acute Blood Loss during Burn and Soft Tissue Excisions: An Observational Study of Blood Product Resuscitation Practices and Focused Review 
The journal of trauma and acute care surgery  2015;78(6 0 1 0 0 0 0 0 6):S39-S47.
Background
Many military and civilian centers have shifted to a Damage Control Resuscitation (DCR) approach, focused on providing oxygen-carrying capacity while simultaneously mitigating coagulopathy with a balanced ratio of platelets and plasma to red blood cells. It is unclear to what degree this strategy is used during burn or soft tissue excision. Here we characterized blood product transfusion during burn and soft tissue surgery, and reviewed the published literature regarding intraoperative coagulation changes. We hypothesized that blood product resuscitation during burn and soft tissue excision is not hemostatic and would be insufficient to address hemorrhage-induced coagulopathy.
Methods
Consented adult patients were enrolled into an IRB-approved prospective observational study. Number, component type, volume, and age of the blood products transfused were recorded during burn excision/grafting or soft tissue debridement. Component bags (pRBCs, FFP, PLTs, and cryoprecipitate) were collected and the remaining sample harvested from the bag and tubing. Aliquots of 1/1000th the original volume of each blood product were obtained and combined, producing an amalgam sample containing the same ratio of product transfused. Platelet count, rotational thromboelastometry, and impedance aggregometry were measured. Significance was set at p<0.05.
Results
Amalgamated transfusate samples produced abnormally weak clots (p≤0.001) particularly if they did not contain platelets. Clot strength (48.8 ± 2.6 mm; reference range: 49–71mm) for platelet-containing amalgams was below the lower limit of the reference range despite PLT:RBC ratios greater than 1:1. Platelet aggregation was abnormally low; transfused platelets were functionally inferior to native platelets.
Conclusion
Our study and focused review demonstrate that further work is needed in order to fully understand the needs of patients undergoing tissue excision. The three studies reviewed and the results of our observational work suggest that coagulopathy and thrombocytopenia may contribute to intraoperative hemorrhage. Blood product resuscitation during burn and soft tissue excision is not hemostatic.
doi:10.1097/TA.0000000000000627
PMCID: PMC4443865  PMID: 26002262
Damage control resuscitation; Burn Excision; Soft tissue excision; Acute traumatic coagulopathy; Severe hemorrhage
25.  Retrospective Analysis of the Blood Component Utilization in a University Hospital of Maximum Medical Care 
Background
Demographic data illustrate clearly that people in highly developed countries get older, and the elderly need more blood transfusions than younger patients. Additionally, special extensive therapies result in an increased consumption of blood components. Beyond that the aging of the population reduces the total number of preferably young and healthy blood donors. Therefore, Patient Blood Management will become more and more important in order to secure an increasing blood supply under fair-minded conditions.
Methods
At the University Hospital of Münster (UKM) a comprehensive retrospective analysis of the utilization of all conventional blood components was performed including all medical and surgical disciplines. In parallel, a new medical reporting system was installed to provide a monthly analysis of the transfusional treatments in the whole infirmary, in every department, and in special blood-consuming cases of interest, as well.
Results
The study refers to all UKM in-patient cases from 2009 to 2011. It clearly demonstrates that older patients (>60 years, 35.2–35.7% of all cases, but 49.4–52.6% of all cases with red blood cell (RBC) transfusions, 36.4–41. 6% of all cases with platelet (PTL, apheresis only) transfusions, 45.2–48.0% of all cases with fresh frozen plasma (FFP) transfusions) need more blood products than younger patients. Male patients (54.4–63.9% of all cases with transfusions) are more susceptible to blood transfusions than female patients (36.1–45.6% of all cases with transfusions). Most blood components are used in cardiac, visceral, and orthopedic surgery (49.3–55.9% of all RBC units, 45.8–61.0% of all FFP units). When regarding medical disciplines, most transfusions are administered to hematologic and oncologic patients (12.9–17.7% of all RBC units, 9.2–12.0% of all FFP units). The consumption of PTL in this special patient cohort (40.6–50.9% of all PTL units) is more pronounced than in all other surgical or in non-surgical disciplines.
Conclusion
The results obtained from our retrospective analysis may help to further optimize the responsible and medical indication-related utilization of blood transfusions as well as the recruitment of blood donors and their timing. It may be also a helpful tool in order to avoid needless transfusions and transfusionassociated adverse events.
doi:10.1159/000337956
PMCID: PMC3364044  PMID: 22670131
Patient blood management; Blood supply; Consumption of blood products; Hemotherapy; Medical reporting system; Demography; Process management; Health services research

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