infusible platelet membrane; platelet substitute; platelet-derived microvesicles; platelet concentrates
pathogen-reduction technology; blood safety; UVC irradiation
aspirin; bleeding; P2Y12 antagonists; thrombin receptor antagonists; von Willebrand factor
organ transplantation; tregs; tolerance induction
Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH.
Material and methods
The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970–1995.
The median age of the patients was 24 years (IQR 18–30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2–6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8–13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR =0.8–3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR =0–1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2,120 IU/kg; IQR 1,514–2,768), was higher than that of MH patients (median 133 IU/kg; IQR 49–468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3–15) vs a median of 2 points, IQR 0–6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population.
When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.
moderate haemophilia; severe haemophilia; comparison; joint bleeding; HJHS
Blood loss during total joint arthroplasty strongly influences the time to recover after surgery and the quality of the recovery. Blood conservation strategies such as pre-operative autologous blood donation and post-operative cell salvage are intended to avoid allogeneic blood transfusions and their associated risks. Although widely investigated, the real effectiveness of these alternative transfusion practices remains controversial.
Materials and methods
The surgery reports of 600 patients undergoing total joint arthroplasty (312 hip and 288 knee replacements) were retrospectively reviewed to assess transfusion needs and related blood management at our institute. Evaluation parameters included post-operative blood loss, haemoglobin concentration measured at different time points, ASA score, and blood transfusion strategies.
Autologous blood donation increased the odds of receiving a red blood cell transfusion. Reinfusion by a cell salvage system of post-operative shed blood was found to limit adverse effects in cases of severe post-operative blood loss. The peri-operative net decrease in haemoglobin concentration was higher in patients who had predeposited autologous blood than in those who had not.
The strengths of this study are the high number of cases and the standardised procedures, all operations having been performed by a single orthopaedic surgeon and a single anaesthesiologist. Our data suggest that a pre-operative autologous donation programme may often be useless, if not harmful. Conversely, the use of a cell salvage system may be effective in reducing the impact of blood transfusion on a patient’s physiological status. Basal haemoglobin concentration emerged as a useful indicator of transfusion probability in total joint replacement procedures.
total hip arthroplasty; total knee arthroplasty; pre-operative autologous blood donation; post-operative blood cell salvage system; blood management
Transfusion therapy remains the main treatment for patients with severe haemoglobinopathies, but can cause adverse reactions which may be classified as immediate or delayed. The use of targeted prevention with drugs and treatments of blood components in selected patients can contribute to reducing the development of some reactions.
The aim of our study was to develop an algorithm capable of guiding behaviours to adopt in order to reduce the incidence of immediate transfusion reactions.
Materials and methods
Immediate transfusion reactions occurring over a 7-year period in 81 patients with transfusion-dependent haemoglobinopathies were recorded. The patients received transfusions with red cell concentrates that had been filtered prestorage. Various measures were undertaken to prevent transfusion reactions: leucoreduction, washing the red blood cells, prophylactic administration of an antihistamine (loratidine 10 mg tablet) or an antipyretic (paracetamol 500 mg tablet).
Over the study period 20,668 red cell concentrates were transfused and 64 adverse transfusion reactions were recorded in 36 patients. The mean incidence of reactions in the 7 years of observation was 3.1‰. Over the years the incidence gradually decreased from 6.8‰ in 2004 to 0.9‰ in 2010.
Preventive measures are not required for patients who have an occasional reaction, because the probability that such a type of reaction recurs is very low. In contrast, the targeted use of drugs such as loratidine or paracetamol, sometimes combined with washing and/or double filtration of red blood cells, can reduce the rate of recurrent (allergic) reactions to about 0.9‰. The system for detecting adverse reactions and training staff involved in transfusion therapy are critical points for reliable collection of data and standardisation of the detection system is recommended for those wanting to monitor the incidence of all adverse reactions, including minor ones.
transfusion; adverse reactions; washed red blood cells; haemovigilance
Haemoglobin screening methods need to be highly sensitive to detect both low and high haemoglobin levels and avoid unnecessary rejection of potential blood donors. The aim of this study was to evaluate the accuracy of measurements by HemoCue in blood donors.
Materials and methods
Three hundred and fourteen randomly selected, prospective blood donors were studied. Single fingerstick blood samples were obtained to determine the donors' haemoglobin levels by HemoCue, while venous blood samples were drawn for measurement of the haemoglobin level by both HemoCue and an automated haematology analyser as the reference method. The sensitivity, specificity, predictive values and correlation between the reference method and HemoCue were assessed. Cases with a haemoglobin concentration in the range of 12.5–17.9 g/dL were accepted for blood donation.
Analysis of paired results showed that haemoglobin levels measured by HemoCue were higher than those measured by the reference method. There was a significant correlation between the reference method and HemoCue for haemoglobin levels less than 12.5 g/dL. The correlation was less strong for increasing haemoglobin levels. Linear correlation was poor for haemoglobin levels over 18 g/dL. Thirteen percent of donors, who had haemoglobin levels close to the upper limit, were unnecessarily rejected.
HemoCue is suitable for screening for anaemia in blood donors. Most donors at Yazd are males and a significant percentage of them have haemoglobin values close to the upper limit for acceptance as a blood donor; since these subjects could be unnecessarily rejected on the basis of HemoCue results and testing with this method is expensive, it is recommended that qualitative methods are used for primary screening and accurate quantitative methods used in clinically suspicious cases or when qualitative methods fail.
blood donors; haemoglobin; haemoglobinometer; HemoCue; false deferral
Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding.
Materials and methods
Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringer’s lactate, PlasmalyteTM) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution.
Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates.
The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk.
haemodilution; coagulation factor concentrates; platelet function; thrombin generation; thromboelastometry
During transportation, platelet concentrates (PC) usually undergo a long period without agitation. Whether this interruption improves quality and viability or, contrariwise, has deleterious effects on PC stored for 48 hours (h) is unknown. The aim of this study was to investigate the effects of metabolic resting (6 h of interruption of agitation) vs continue agitation of PC stored for 48 h in the blood bank of Tehran.
Materials and methods
PC were prepared from platelet-rich plasma and stored in permeable bags in a shaker/incubator for 42 h at room temperature (20–24 ºC). Then, simply by stopping the agitator, the PC remained stationary (“resting”) without agitation for 6 h (WCA6h), prior to transfusion. In vitro measurements of platelet quality were carried out just after completion of the resting period and the results were compared with those of PC continuously agitated in the same day (designated as the control group, CA6h). The in vitro variables measured were swirling, ristocetin-induced aggregation (GPIb-related function), lactate dehydrogenase (LDH) concentration, platelet factor 4 (PF4) release and P-selectin expression (activation markers).
The mean platelet counts of the control group (CA6h) and rested (WCA6h) PC were not statistically different (P =0.548). Likewise, the mean pH values were not significantly different: WCA6h (7.16±0.08) and CA6h (7.22±0.16) (P =0.300). Although ristocetin-induced aggregation did not differ significantly between CA6h (79.2±4.4) and WCA6h (66.65±28.55) (P =0.186), WCA6h showed significantly less PFA release (P =0.015) and lower P-selectin expression (P =0.006).
We observed that PC stored under agitation for 42 h at 22–24 ºC in permeable bags and then rested for 6 h had better preserved pH, swirling and LDH and less platelet activation then PC kept under continuous agitation for the whole 48 h storage period.
platelet resting; metabolism; agitation effect; PF4; P-selectin
Volume reduction is a widely used procedure in umbilical cord blood banking. It concentrates progenitor cells by reducing plasma and red blood cells, thereby optimising the use of storage space. Sepax and AXP are automated systems specifically developed for umbilical cord blood processing. These systems basically consist of a bag processing set into which cord blood is transferred and a device that automatically separates the different components during centrifugation.
The aim of this study was to analyse and compare cell recovery of umbilical cord blood units processed with Sepax and AXP at Valencia Cord Blood Bank. Cell counts were performed before and after volume reduction with AXP and Sepax.
When analysing all the data (n =1,000 for AXP and n= 670 for Sepax), the percentages of total nucleated cell recovery and red blood cell depletion were 76.76±7.51% and 88.28±5.62%, respectively, for AXP and 78.81±7.25% and 88.32±7.94%, respectively, for Sepax (P <0.005 for both variables). CD34+ cell recovery and viability in umbilical cord blood units were similar with both devices. Mononuclear cell recovery was significantly higher when the Sepax system was used.
Both the Sepax and AXP automated systems achieve acceptable total nucleated cell recovery and good CD34+ cell recovery after volume reduction of umbilical cord blood units and maintain cell viability. It should be noted that total nucleated cell recovery is significantly better with the Sepax system. Both systems deplete red blood cells efficiently, especially AXP which works without hydroxyethyl starch.
cord blood; volume reduction; haematopoietic progenitors
Point-of-care thromboelastometry (ROTEM®) can be used to assess coagulation in whole blood. In the ROTEM® FIBTEM test, cytochalasin D eliminates the contribution of platelets to the whole blood clot; hence, only the remaining elements, including fibrinogen/fibrin, red blood cells and factor XIII, contribute to clot strength. We investigated the relationships between FIBTEM maximum clot firmness (MCF), whole blood fibrinogen concentration and plasma fibrinogen concentration to determine the impact of haematocrit on these parameters during cardiac surgery.
Materials and methods
The relationships between FIBTEM MCF and both whole blood fibrinogen concentration and plasma fibrinogen concentration (Clauss assay) were evaluated pre-operatively and after cardiopulmonary bypass/protamine administration in haematocrit-based subgroups.
The study included 157 patients. The correlation coefficient rho between FIBTEM MCF and plasma fibrinogen concentration was 0.68 at baseline and 0.70 after protamine, while that between FIBTEM MCF and whole blood fibrinogen concentration was 0.74 at baseline and 0.72 after protamine (all P <0.001). In subgroup analyses based on haematocrit levels, pre-operative FIBTEM MCF and whole blood fibrinogen concentration were both significantly higher (P <0.05) for the lowest haematocrit subgroup, but plasma fibrinogen concentration was similar in all groups. After protamine, no significant differences were observed between the lowest haematocrit group and the other groups for any of the three parameters.
The effect of haematocrit on blood clotting is not reflected by plasma fibrinogen concentration, in contrast to FIBTEM MCF which incorporates the contribution of haematocrit to whole blood clot firmness. This effect does, however, appear to be negligible in haemodiluted patients.
cardiac surgery; fibrinogen; FIBTEM; haematocrit; thromboelastometry
Premature babies may receive multiple transfusions during the first weeks of their life. Strong associations exist between the receipt of blood transfusions and the development of the major consequences of prematurity such as retinopathy and chronic lung disease. The possible physiological link between the receipt of blood and disease is unclear, but iron-induced oxidative damage and/or bacterial colonisation would promote these conditions. Premature babies are poorly equipped to deal with any increases in iron and oxidative load that they may acquire via blood transfusions. To determine whether there are any relationships between these factors, we studied iron and oxidative status of just expired (i.e. 36 days old) paediatric red blood cell (RBC) packs.
Materials and methods
Just expired paediatric RBC packs were obtained from the local blood bank. The extracellular medium surrounding the RBC was separated by centrifugation and the following parameters measured: total iron concentration, total iron binding capacity, non-transferrin-bound iron [NTBI], haemoglobin, total and reduced ascorbate, and malondialdehyde concentration.
The extracellular fluid of the paediatric packs (n =13) was rich in iron, a high percentage of which (36%) was present as potentially toxic NTBI. It was highly redox active with limited antioxidant protection and iron-binding capacity.
The extracellular medium surrounding packed RBC could potentially be toxic if administered to patients with limited iron sequestering and antioxidant capacity, such as premature babies. Further studies are required to determine at what point during storage these changes become potentially harmful so that clinical studies can examine the optimal storage time for blood destined for premature babies.
iron; oxidative stress; packed red blood cells; storage
Prediction of transfusion is presumed to reduce wastage rates in pre-operative autologus blood donation (PABD) and unnecessary providing and cross-matching in allogeneic transfusion. The clinical utility of published algorithms in predicting transfusions was analysed.
Materials and methods
In a cohort of 195 patients undergoing total hip arthroplasty, after PABD, expected transfusion needs were predicted with two published algorithms (A and B). The algorithms were then compared to actual transfusions. Assumptions and formulae of these algorithms were varied in an attempt to improve their prognostic utility.
The optimal variation of A resulted in allogeneic transfusions (PABD setting) or uncross-matched transfusions (allogeneic setting) of 27.3%, and a wastage rate of autologous units or unnecessary cross-matching of 73.8%, compared to 33.3% and 76.6%, respectively, for the original algorithm. The original version of algorithm B resulted in (allogeneic) transfusions of 78.8%, and a wastage rate or unnecessary cross-matching of 46.2%. The former could be improved by a variation of the algorithm to 69.7%. Comparing the optimal variations of both algorithms, the more elaborate algorithm A reduced overall transfusion risk significantly better (P =0.001). The two algorithms were not statistically different in reducing resource consumption (P =0.09).
Although the prognostic utility of algorithm A was significantly better for reducing overall transfusion risk, both algorithms were unable to meaningfully identify patients who would benefit from PABD or cross-matching. The algorithms could not increase the percentage of PABD patients transfused, or the percentage of cross-matched patients transfused in the allogeneic setting. Furthermore, they could neither reduce transfusion risk nor resource consumption.
allogeneic transfusion; clinical prediction rule; pre-operative autologous blood donation; primary total hip arthroplasty; transfusion risk
Timely and efficient recall of products known or suspected to be non-conforming is an important measure in the prevention of adverse events and in patients' safety. Product recall in the transfusion service is regulated by professional standards and legal acts, but publications presenting results related to the implementation of these procedures are quite rare.
Materials and methods
Data from the Croatian Institute of Transfusion Medicine (CITM) on the procedures of product recall during an 11-year period (2000–2010) were retrospectively analyzed. Reasons for product recall, their frequency, level of severity and efficiency of the procedures are presented and discussed.
During the study period, there were 245 procedures of product recall, for an average of 22 (18–29) procedures/year, all of low extent (1–25 products). Recall was required for 1/3,571 blood products issued, while the frequency of laboratory test report recalls was 1/5,447 patients. The leading reasons for product recall were suspected bacterial contamination of blood products (30.2%) and suspected or demonstrated non-conformity of laboratory test reports (28.6%). In total, 99 (40.4%) product recalls were categorized as class I, 30 (12.2%) as class II and 116 (47.3%) as class III.
According to the available literature data, the product recall procedures were performed quite infrequently by the CITM and were of low extent. There was a remarkable decreasing trend in the rate of product recall due to non-conformities or errors made at the CITM, along with a constant or increasing rate of recalls because of biological variability of blood products.
recall; blood products; test reports
In 2001, the criteria for blood donor eligibility in Italy were modified by a ministerial decree from a permanent deferral for "men who have sex with men" to an individual risk assessment of sexual behaviours. The aim of this study was to evaluate the impact of this change in donor screening criteria on the human immunodeficiency virus epidemic among blood donors in Italy.
Materials and methods
We used the data obtained from the Italian blood donor epidemiological surveillance system. We compared data collected in 2009 and 2010, when the individual risk assessment policy was applied, with data collected in 1999 when permanent deferral was applied for men who have sex with men based on a declaration of sexual orientation. We evaluated the change over time in the relative proportion of HIV antibody-positive donors who likely acquired the infection from men who have sex with men vs heterosexual sexual exposure; the relative risk was calculated using 1999 as the reference year.
In all 3 years, the majority of HIV antibody-positive donors reported sexual exposure as a risk factor for HIV infection; this proportion increased over time, although not statistically significantly. Heterosexuals always accounted for at least 40% of all HIV antibody-positive cases. The rate of HIV antibody-positive donors increased similarly in men who have sex with men and heterosexuals; specifically, the rate of HIV antibody-positive cases per 100,000 donors was more than 2-fold higher among men who have sex with men in 2009–2010 than in 1999 (2009–2010 vs 1999, RR =2.8; P =0.06), and that among heterosexuals was 1.5 fold higher (P =0.18).
When comparing the period before (1999) and after (2009–2010), the implementation of the individual risk assesment policy in 2001, no significant increase in the proportion of men who have sex with men compared to heterosexuals was observed among HIV antibody-positive blood donors, suggesting that the change in donor deferral policy did not lead to a disproportionate increase of HIV-seropositive men who have sex with men.
blood donors; HIV infection; sexual behaviour; MSM; heterosexual
RhD alloimmunisation; antibody investigation; anti-D and anti-C specificity; anti-G
anaemia; trauma; Jehovah’s Witness; refusal of transfusion
Erb antigen; haemolytic disease of the newborn; low incidence antigens
Lewis blood group; transfusion; transfusion reaction