Potential of a second screening test for alloimmunization in pregnancies of Rhesus-positive women: a Swedish population- based cohort study.

INTRODUCTION: There is lack of consensus regarding whether a second screening in Rhesus-positive pregnant women is worthwhile, with different guidelines, recommendations, and practices. We aimed to estimate the number and timing of missed alloimmunizations in Rhesus-positive pregnancies screened once and weigh the relative burden of additional screening and monitoring versus the estimated reduction in adverse pregnancy outcomes. METHODS: We extracted information on maternal, pregnancy, and screening results for 682,126 pregnancies for 2003-2012 from Swedish national registers. We used data from counties with a routine second screening to develop and validate a logistic model for a positive second test after an earlier negative. We used this model to predict the number of missed alloimmunizations in counties offering only one screening. Interval-censored survival analysis identified an optimal time window for a second test. We compared the burden of additional screening with estimated adverse pregnancy outcomes avoided. RESULTS: The model provided an accurate estimate of positive tests at second screening. For counties with the lowest screening rates, we estimated that a second screening would increase the alloimmunization prevalence by 33% (from 0.19% to 0.25%), detecting the 25% (304/1222) of cases that are currently missed. The suggested timing of a second screen was gestational week 28.For pregnancies currently screened once, the estimated cost of a second test followed by maternal monitoring was approximately 10% the cost incurred by the excess adverse pregnancy outcomes. CONCLUSION: Investment in routine second screening can identify many alloimmunizations that currently go undetected or are detected late, with the potential for cost savings.

Red blood cell alloimmunization in myelodysplastic syndromes: Associations with sex, DAT-positivity, and increased transfusion needs.

BACKGROUND: Many patients with myelodysplastic syndromes (MDS) need repeated red blood cell transfusions which entails a risk of immunization and antibody formation. Associations between alloantibodies, autoantibodies and increased transfusion requirements have been reported, but their relationship remains unclear. In this study, we analyzed factors potentially associated with red blood cell alloimmunization, as well as changes in transfusion intensity and post-transfusion hemoglobin increments. METHODS: In a retrospective cohort study, we linked Swedish MDS patients diagnosed between 2003 and 2017 to transfusion and immunohematology data. Potentially associated factors were analyzed using Cox proportional hazards regression. The transfusion rate after detected alloimmunization was analyzed using a fixed effects Poisson regression. Post-transfusion hemoglobin increments before and after alloimmunization were compared using a mixed effects regression. RESULTS: Alloantibodies following MDS diagnosis were detected in 50 out of 429 patients (11.7%). Female sex and a positive direct antiglobulin test (DAT) were independently associated with alloimmunization, with hazard ratios of 2.02 (95% confidence interval [CI] 1.08-3.78) and 9.72 (95% CI, 5.31-17.74), respectively. The transfusion rate following alloimmunization was increased with an incidence rate ratio of 1.33 (95% CI, 0.98-1.80) and the post-transfusion hemoglobin increment after alloimmunization was 1.40 g/L (95% CI, 0.52-2.28) lower per red blood cell unit (p = .002) compared to before alloimmunization, in multivariable analyses. DISCUSSION: Alloimmunization against blood group antigens was associated with sex, DAT-positivity, increased transfusion needs, and lower post-transfusion hemoglobin increments. These findings warrant further investigation to evaluate the clinical significance of up-front typing and prophylactic antigen matching in patients with MDS.

Cryopreserved Platelets in a Non-Toxic DMSO-Free Solution Maintain Hemostatic Function In Vitro.

Dimethyl sulfoxide (DMSO) is regularly used as a cryoprotectant agent for the cryopreservation of platelets. However, DMSO is considered toxic. We therefore hypothesized that saline could be used as a non-toxic medium for the cryopreservation of platelets. Double-dose buffy coat platelets (n = 10) were divided and cryopreserved at -80 °C using 5-6% dimethyl sulfoxide (DMSO) or in NaCl (9 mg/mL). Paired testing was conducted pre-freeze, post-thaw (PT 1 h). Upon analysis, each bag was thawed and reconstituted in fresh plasma. Analyses included cell counts and the metabolic, phenotypic, and functional properties of the platelets together with thromboelastometry. The cryopreserved platelets showed several biochemical and ultrastructural changes compared to pre-freezing. Platelet recovery was approximately 17% higher in DMSO-free units (p < 0.001), but the platelet viability was reduced (p < 0.001). However, using controlled freezing (n = 6), the platelet viability was improved. The clot formation time (CFT) was comparable, but DMSO-free platelets showed slightly decreased maximum clot firmness (MCF) (p = 0.034). By reducing the reconstituted plasma volume, a reduced CFT and increased MCF were obtained (p < 0.001). This study demonstrates that platelets can be cryopreserved in saline without the addition of DMSO, with high recovery and maintained hemostatic function. However, controlled freezing is required to optimize platelet quality.

Single-exon approach to non-invasive fetal RHD screening in early pregnancy: An update after 10 years' experience.

BACKGROUND AND OBJECTIVES: Anti-D prophylaxis, administered to RhD-negative women, has significantly reduced the incidence of RhD immunization. Non-invasive fetal RHD screening has been used in Stockholm for more than 10 years to identify women who will benefit from prophylaxis. The method is based on a single-exon approach and is used in early pregnancy. The aim of this study was to update the performance of the method. MATERIALS AND METHODS: The single exon assay from Devyser AB is a multiplex kit detecting both exon 4 of the RHD gene and the housekeeping gene GAPDH. Cell-free DNA was extracted from 1 ml of plasma from EDTA blood taken during early pregnancy, weeks 10-12. The genetic RHD results were compared with serological typing of newborns for a determination of sensitivity and specificity. RESULTS: In total, 4337 pregnancies were included in the study; 44 samples (1%) were inconclusive either due to maternal RHD gene variants (n = 34) or technical reasons (n = 10). Of the remaining 4293 pregnancies, a total number of nine discrepant results were found. False positive results (n = 7) were mainly (n = 4) due to RHD gene variants in the child. False-negative results were found in two cases, of which one was caused by a technical error. None of the false-negative cases was due to RHD gene variants. Overall, the sensitivity of the method was 99.93% and specificity 99.56%. CONCLUSION: The single-exon assay used in this study is correlated with high sensitivity and specificity.

Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations.

BACKGROUND AND OBJECTIVES: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. MATERIALS AND METHODS: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. RESULTS: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. CONCLUSION: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.

Cryopreservation of buffy coat derived platelets: Paired in vitro characterization using uncontrolled versus controlled freezing rate protocols.

BACKGROUND: Cryopreserved platelets show a reduced recovery and viability after freezing and thawing including several ultrastructural and phenotypic deteriorations compared with liquid-stored platelets. It is suggested that using Controlled-Rate Freezing (CRF) can reduce variability and optimize the functionality profile for cells. The objective of the study is to compare cellular, metabolic, phenotypic and functional effects on platelets after cryopreservation using different freezing rate protocols. STUDY DESIGN AND METHODS: To evaluate the possible effects of different freezing rate protocols a two-experimental study comparing diverse combinations was tested with a pool and split design. Uncontrolled freezing of platelets in materials with different thermal conductivity (metal vs cardboard) was evaluated in experiment 1. Experiment 2 evaluated uncontrolled vs a controlled-rate freezing protocol in metal boxes. All variables were assessed pre and post cryopreservation. RESULTS: Directly after thawing, no major differences in platelet recovery, LDH, ATP, Δψ, CD62P, CD42b, platelet endothelial cell adhesion molecule and sCD40L were seen between units frozen with different thermal conductivity for temperature. In contrast, we observed signs of increased activation after freezing using the CRF protocol, reflected by increased cell surface expression of CD62P, PAC-1 binding and increased concentration of LDH. Agonist induced expression of a conformational epitope on the GPIIb/IIIa complex and contribution to blood coagulation in an experimental rotational thromboelastometry setup were not statistically different between the groups. CONCLUSION: The use of a uncontrolled freezing rate protocol is feasible, creating a platelet product comparable to using a controlled rate freezing equipment during cryopreservation of platelets.

Patterns of red-cell transfusion use in obstetric practice in sweden 2003-2017: A nationwide study.

BACKGROUND: There is a paucity of data on patterns of red-cell transfusions in obstetrical care, but some studies have suggested an increase in transfusion rates during the last decade. The purpose of this study was to investigate maternal characteristics, temporal trends and hospital variations in red-cell use in a large contemporary obstetric cohort in Sweden. STUDY DESIGN AND METHODS: Nationwide observational cohort study of maternal red-cell transfusions for all deliveries in Sweden between 2003 and 2017. RESULTS: The proportion of deliveries that received red-cell transfusions was stable during the study period, although the number of red-cell units administered per delivery declined. Among transfused women, most received a low-volume transfusion of 1 or 2 units. Red-cell transfusion was more common among the nulliparous, for instrumental and caesarean deliveries, and with increased maternal age. We saw large variations in transfusion rates between hospitals in Sweden, despite adjusting for age and parity. CONCLUSIONS: In comparison to other high-resource countries we see a high proportion of deliveries with maternal red-cell transfusions. However, we do not see an increase in red-cell use over time.

Altered strategy of prophylactic anti-D administration in pregnancy to cover term and post-term - a pilot study.

BACKGROUND AND OBJECTIVE: Routine antenatal anti-D prophylaxis (RAADP) to RhD-negative women is most often administered in gestational age (GA) 28-30 weeks with the next anti-D dose administered postpartum. The aim of this study was to analyse the proportion of RhD-negative women where RAADP is not detectable at term and in a pilot study to investigate whether RAADP administered in GA 28 and 38 results in detectable levels at term, post-term and post-delivery. MATERIALS AND METHODS: In a retrospective analysis, 4280 RhD-negative women carrying an RHD positive fetus were included and the proportion with a negative antibody screen at delivery was determined. In the second part, 39 pregnancies were included prospectively, a second dose of RAADP was administered in GA 38 weeks, and anti-D was quantified before the second dose and then weekly for 5 weeks. RESULTS: In the retrospective analysis, 20·5% (856/4280) with RAADP administered in GA 28 were negative in routine antibody screening at delivery. In the small prospective study, 18% (7/39) had a negative antibody screen and 26% (10/39) had levels below 0·005 IU/ml, in the quantification assay, in GA 38. Anti-D prophylaxis administered in GA 38 showed detectable levels of anti-D up to 30 days post-delivery, with concentration at delivery 0·060 ± 0·034 IU/ml (mean ± SD). CONCLUSION: Approximately 20% of the RhD-negative women show non-detectable levels of anti-D at term. A second dose of RAADP at GA 38 results in stable concentrations of anti-D at term, post-term and post-delivery, but with large interindividual variation.

Rotational thromboelastometry results are associated with care level in COVID-19.

High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.

Management and clinical consequences of red blood cell antibodies in pregnancy: A population-based cohort study.

INTRODUCTION: Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines. MATERIAL AND METHODS: A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies. RESULTS: Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38+5  weeks compared with 35+5  weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%]). CONCLUSIONS: Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments.

Patterns of blood use in Sweden from 2008 to 2017: A nationwide cohort study.

BACKGROUND: Transfusion patterns in Sweden have not been characterized on a nationwide level. STUDY DESIGN AND METHODS: We conducted a nationwide descriptive cohort study in Sweden from 2008 to 2017. Data on blood donors, donations, component manufacture, transfusions, and transfused patients were extracted from Swedish portion of the Scandinavian Donations and Transfusions (SCANDAT3-S) database. RESULTS: A total of 708 436 patients received 5 587 684 red cell, plasma, or platelet transfusions during the study period. The age-standardized transfusion rate decreased markedly during the study period for red cell units (from 53 to 39 units/1000 persons) and plasma units (from 11 to 4.9 units/1000 persons), but remained relatively constant for platelet concentrates. The transfusion rate was 30%-40% higher in males than in females in the first year of life, and higher in males over 45 years than in females. Between age 20 and 45, the majority of red cells were transfused to female patients with obstetric indications, whereas trauma was the predominant indication for male contemporaries. In females over 80 years, the largest proportion of red cells were administered due to trauma. Overall, hematological patients received 36% of all platelet units. There were large regional differences in transfusion rates for red cell units, ranging from less than 30 to greater than 60/1000 persons. CONCLUSION: Transfusion rates in Sweden remain high but have decreased strikingly during the study period - with the exception of platelet transfusions. Based on the available data, it is difficult to draw firm conclusions about whether transfusion rates can be further reduced.

No evidence of transfusion transmitted sporadic Creutzfeldt-Jakob disease: results from a bi-national cohort study.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self-catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion. METHODS AND STUDY DESIGN: A retrospective cohort study was performed, using data from the bi-national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis. RESULTS: We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred. DISCUSSION: Using data from a large, bi-national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted.

Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) Working Group.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. MATERIALS AND METHODS: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. RESULTS: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. CONCLUSION: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.

Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia.

Anti-HPA-1a-antibodies are the main cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT) which may result in intracranial hemorrhage (ICH) and death among fetuses and newborns. Advances in understanding the pathogenesis of FNAIT and proof of concept for prophylaxis to prevent immunization suggest that development of hyperimmune anti-HPA-1a IgG aimed at preventing immunization against HPA-1a and FNAIT is feasible. Anti-HPA-1a IgG can be obtained either by isolating immunoglobulin from already-immunized women or by development of monoclonal anti-HPA-1a antibodies. Here we discuss recent advances that may lead to the development of a prenatal and postnatal prophylactic treatment for the prevention of HPA-1a-associated FNAIT and life-threatening FNAIT-induced complications.

Platelet consumption and hyperreactivity coexist in experimental traumatic hemorrhagic model.

INTRODUCTION: Platelets are critical for hemostasis, and a low platelet count predicts mortality in trauma. The role of platelet dysfunction in severe traumatic hemorrhage and coagulopathy needs to be further defined. The aim of this study was to evaluate the platelet function in a new model of experimental traumatic hemorrhage. MATERIAL AND METHODS: New Zealand white rabbits (n = 10) were subjected to tracheostomy and trauma laparotomy, and then bilateral femur fractures with 40% hemorrhage of their estimated blood volume. Arterial blood gases, standard coagulation tests, mean platelet volume, platelet aggregation using impedance aggregometry with agonist collagen, arachidonic acid (ASPI), and adenosine diphosphate (ADP), rotational thromboelastometry, and fibrinogen binding of platelets were analyzed using flow cytometry. RESULTS: After traumatic hemorrhage, there was a significant physiological response with a rise in lactate (P < .001) and a decrease in base excess (P < .001) and temperature (P < .001). Platelet count decreased from a mean of 244x109/L to 94 x109/L (P = .004) and the mean platelet volume increased from 5.1fL to 6.1fL (P = .002). Impedance aggregometry with the agonist collagen, ASPI, and ADP was all significantly decreased after hemorrhage (P = .007). However, there was an increased fibrinogen binding of ADP-activated platelets after traumatic hemorrhage analyzed by flow cytometry (P < .05). CONCLUSIONS: This traumatic hemorrhage model presents two parallel pathophysiological responses of platelets; platelet consumption as evidenced by a significant decrease in platelet count and aggregation, and platelet hyperreactivity as shown by a higher mean platelet volume and enhanced platelet fibrinogen binding. Further studies are needed to characterize these different aspects of platelet function in severe traumatic hemorrhage.

Platelet function analysed by ROTEM platelet in cardiac surgery after cardiopulmonary bypass and platelet transfusion.

OBJECTIVES: The aim of this study was to investigate whether ROTEM platelet can provide additional information to the traditional ROTEM analysis to guide treatment with platelet transfusions in cardiac surgery and to identify factors triggering platelet administration. BACKGROUND: Platelets play a crucial role in coagulation and haemostasis after cardiac surgery. Excessive bleeding after cardiopulmonary bypass usually requires transfusions of blood products, including platelets. The ROTEM platelet is a novel point-of-care analysis for whole blood. MATERIALS AND METHODS: We included 23 patients scheduled for complex cardiac surgery. ROTEM (in-tem, ex-tem), ROTEM platelet (ARA-tem, ADP-tem and TRAP-tem) and platelet count were analysed before induction of anaesthesia (T0), after cardiopulmonary bypass and protamine reversal (T1) and after platelet transfusion (T2, n = 10). RESULTS: ROTEM and ROTEM platelet tests were all significantly reduced between T0 and T1. ROTEM parameters improved significantly after platelet transfusion. Regarding ROTEM platelet, only TRAP-tem increased between T1 and T2 (P = .008). Factors triggering platelet transfusion were long duration of surgery and time on cardiopulmonary bypass. CONCLUSION: ROTEM platelet with thrombin activation, TRAP-tem, improved significantly, indicating that platelet transfusion may reverse cardiopulmonary bypass-induced platelet dysfunction. Further studies are needed to evaluate whether TRAP-tem can be a valuable analysis regarding indications for transfusion of platelets after extensive cardiac surgery.

Transmission of viral hepatitis through blood transfusion in Sweden, 1968 to 2012.

IntroductionViral hepatitis remains a significant threat to transfusion safety, although largely mitigated by donor screening.AimOur objective was to estimate the past and present burden of transfusion transmission of all types of viral hepatitis (A to E) and to find undiagnosed infections with hepatitis C virus (HCV).MethodWe performed a retrospective cohort study using a database of the entire computerised transfusion experience of Sweden from 1968 to 2012 and linking it to a nationwide database of notifiable infections. We then used two independent statistical approaches. Firstly, we tracked recipients of blood from donors with confirmed viral hepatitis. Secondly, we computed a donor-specific risk score, defined as the difference between the observed and the expected number of HCV infections among all previous recipients of all donors, where thresholds were determined using simulation.ResultsAmong 1,146,307 transfused patients, more than 5,000 were infected with HCV. Transfusion transmission only occurred before 1992 when donor screening had been completely implemented. Overall, we found 44 donors and 1,180 recipients likely to be infected with HCV who were still alive but who remained undiagnosed.ConclusionThere is still a substantial number of individuals in Sweden who have probably been infected with HCV through blood transfusion and who are still unaware of their infection. We recommend that a follow-up study should be conducted to validate the method we used by approaching these individuals and offer testing. This would also serve as an opportunity to offer treatment to those who remain infected.

Clinical and Budget Impact of Treating Preoperative Anemia in Major Orthopedic Surgery-A Retrospective Observational Study.

BACKGROUND: Preoperative anemia (POA) in elective surgery is associated with worse outcome. In this retrospective study, in elective hip and knee arthroplasties, the prevalence of POA and its associations with outcome were analyzed, followed by a model estimating the budget impact of screening and treatment of POA. METHODS: All elective hip/knee arthroplasties performed during the period 2016-2018 were included. Patients with normal hemoglobin and patients with POA (hemoglobin < 13.0 g/dL in men and <12.0 g/dL in women) were compared. Outcome measures were allogeneic blood transfusion (ABT), length of stay (LOS), complications, mortality, and costs. The budget impact of screening for POA and treatment with intravenous iron when relevant was modeled based on the results of the costs related to POA. RESULTS: In 881 procedures, the prevalence of POA was 21.5%. POA independently predicted increased risks of ABT (odds ratio [OR]adj, 9.5 [confidence interval-CI, 6.4-13.9]), prolonged LOS (ORadj, 2.8 [CI, 1.8-4.2]), and was associated with increased complications (ORadj, 1.9 [CI, 0.7-4.9]) and mortality (ORadj, 3.2 [CI, 0.8-13.5]). POA resulted in increased costs per patient (P < .001). The budget impact model showed a cost reduction of 254 euros per patient based on the assumption that patients screened and treated for iron-deficient anemia would have the same outcome as non-POA. CONCLUSION: The prevalence of POA in elective orthopedic surgery in Sweden is at the same level as previously reported by others. Screening and treatment of POA would reduce costs based on less ABT and decreased LOS and may reduce complications in elective major orthopedic surgery.

HLA-selected platelets for platelet refractory patients with HLA antibodies: a single-center experience.

BACKGROUND: Platelet refractoriness due to HLA immunization represents a problem in transfusion management of thrombocytopenic hematology patients. Refractory patients can be managed by HLA-selected platelet transfusions, but the optimal matching strategy is debated and how the degree of HLA mismatch influences transfusion outcome is poorly studied. STUDY DESIGN AND METHODS: We studied 32 hematology patients who received 142 matched platelet units between 2007 and 2016. Four matching strategies were compared: 1) genomic HLA typing at the two digit level, performed using polymerase chain reaction-sequence-specific oligonucleotide probing; 2) serologic "eplet score" calculated using HLAMatchmaker; 3) cross-matching using lymphocyte cytotoxicity; and 4) matching based on donor-specific antibody (DSA) specificity, determined using Luminex. A 1-hour corrected count increment (CCI) of more than 7.5 × 109 /L was considered a successful response. RESULTS: Selection of platelets with either a complete HLA match or an acceptable HLA mismatch based on genomic typing and DSA information, each predicted 86% successful transfusion responses. For HLA-mismatched transfusions, the eplet score correlated with CCI and the fraction of successful transfusions, but less well compared to DSA matching. Cytotoxic crossmatching was least predictive. For transfusions across one to four DSAs, the antibody reaction strength correlated with the 1-hour CCI, but many transfusions were successful despite the presence of DSA. CONCLUSION: A complete HLA-A and -B match or an acceptable mismatch based on DSA should guide identification of donors. Still, transfusions across DSAs are often successful, emphasizing that the presence of DSA is necessary but not sufficient for platelet clearance.

Not all red cell concentrate units are equivalent: international survey of processing and in vitro quality data.

INTRODUCTION: In vitro qualitative differences exist in red cell concentrates (RCCs) units processed from whole blood (WB) depending on the method of processing. Minimal literature exists on differences in processing and variability in quality data. Therefore, we collected information from blood manufacturers worldwide regarding (1) details of WB collection and processing used to produce RCCs and (2) quality parameters and testing as part of routine quality programmes. METHODS: A secure web-based survey was developed, refined after pilot data collection and distributed to blood centres. Descriptive analyses were performed. RESULTS: Data from ten blood centres in nine countries were collected. Six blood centres (60%) processed RCCs using the top-and-top (TAT) method which produces RCCs and plasma, and eight centres (80%) used the bottom-and-top (BAT) which additionally produces buffy coat platelets. Five of the centres used both processing methods; however, four favoured BAT processing. One centre utilized the Reveos automated system exclusively. All centres performed pre-storage leucoreduction. Other parameters demonstrated variability, including active cooling at collection, length of hold before processing, donor haemoglobin limits, acceptable collection weights, collection sets, time to leucoreduction, centrifugation speeds, extraction devices and maximum RCC shelf life. Quality marker testing also differed amongst blood centres. Trends towards higher RCC unit volume, haemolysis and residual leucoctyes were seen in the TAT compared with BAT processing across centres. CONCLUSION: Methods and parameters of WB processing and quality testing of RCCs differ amongst surveyed blood manufacturers. Further studies are needed to assess variations and to potentially improve methods and product quality.