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.

Rapid Detection of Apixaban by a ROTEM-Based Approach and Reversibility with Andexanet Alfa or DOAC-Stop.

Background A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis. Objective This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV). Method ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20-500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CT diff ). Results Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CT diff data were similar. Patient sample data were obtained within 20 minutes from sampling. Conclusion Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings.

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.

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.

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.

[Patient blood management - to transfuse blood on appropriate indications]. / Transfusionsstrategi ­ att ge blod på rätt indikation - I Sverige ges fler blodtransfusioner än i jämförbara länder ­ restriktiv policy ger inte sämre vårdresultat.

During the last decade, the varying use and the lack of consistent indications for blood transfusions have been questioned. Comparisons of liberal and restrictive transfusion policies, most often support a restrictive policy. This has led to an evidence-based approach to optimizing the care of patients who might need transfusion, Patient Blood Management (PBM). There is evidence that both anemia and allogeneic blood transfusions are independently associated with increased morbidity and mortality. In elective surgery it is possible to adapt the three pillars of PBM in a structured way; i.e. optimization of red blood cell mass, reduction of blood loss and bleeding, and optimization of the patient's physiological tolerance towards anemia. These activities should be included in the pre-peri- and postoperative routines, in all surgical units.

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.

Cryopreservation of buffy coat-derived platelet concentrates photochemically treated with amotosalen and UVA light.

BACKGROUND: Cryopreserved platelets (CPPs) are considered a promising approach for extended platelet storage, bridging inventory shortages of conventionally stored platelets. It is unknown if platelet concentrates exposed to photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) light, to inactivate pathogens, are suitable for freezing. The objective of this study was to analyze potential effects of PCT on CPPs as compared with untreated CPPs. STUDY DESIGN AND METHODS: A total of 12 PCT-treated and 12 untreated platelet units from buffy coats were cryopreserved at -80°C in 5% dimethyl sulfoxide. CPPs of both types were rapidly thawed at 37°C and resuspended in 200 mL fresh plasma. In vitro properties were analyzed prefreezing, postfreezing and thawing, and on Day 1 after thawing. RESULTS: Directly after thawing, no major differences in platelet content, lactase hydrogenase, adenosine triphosphate, mitochondrial membrane potential, CD62P, CD42b, and platelet endothelial cell adhesion molecule were seen between PCT-CPPs and conventional CPPs. Agonist-induced PAC-1 expression and contribution of CPPs to blood coagulation in an experimental rotational thromboelastometry setup were also similar between the groups. On Day 1 after thawing, the CPPs of both types performed less well. The PCT-CPPs tended to be more affected by the freezing process than the conventional CPPs. CONCLUSIONS: PCT-CPPs appeared slightly more susceptible to lesion effects by freezing than conventional CPPs, in particular in assays on Day 1 after thawing, but these differences were small relative to the dramatic effects of the freezing process itself.

Evaluation of a Decision Tree for Efficient Antenatal Red Blood Cell Antibody Screening.

BACKGROUND: Hemolytic disease of the fetus and newborn due to maternal red blood cell alloimmunization can have serious consequences. Because early detection enables careful monitoring of affected pregnancies, programs to routinely screen all pregnant women have been widely adopted. Due to the low prevalence of alloimmunization, these require large investments of resources to detect a small number of cases. METHODS: We conducted a validation study of a decision tree developed in the Netherlands for determining whether to screen for alloimmunization. In a Swedish cohort, we compared the performance of that decision tree to two alternative models that used maternal characteristics, obstetric history, and transfusion history to identify high-risk women for screening or low-risk women who might be exempt from screening. The models were compared for predictive ability and potential reduction in the volume of screening. RESULTS: The decision tree applied to our study population identified 89% of alloimmunized women with a negative predictive value (NPV) of 99.7% by screening 62% of the population. To achieve the same NPV, our model exempting low-risk women captured 90% of alloimmunizations by screening 63% of the population. In contrast, the model identifying high-risk women for screening while maintaining a similar NPV captured 63% of alloimmunized women by screening 20% of the population. CONCLUSIONS: We validated that an existing decision tree for selecting women for maternal screening performed well in our population, identifying a large proportion of women who became alloimmunized, with a predictive performance almost identical to that of a more elaborate model.

Blood use in hematologic malignancies: a nationwide overview in Sweden between 2000 and 2010.

BACKGROUND: Patients with hematologic malignancies receive large numbers of blood transfusions, and transfusion practices for this patient group are increasingly being scrutinized by randomized controlled trials. However, no studies so far have presented current transfusion statistics on a population level for this patient group. STUDY DESIGN AND METHODS: A retrospective descriptive study was conducted that was based on the Scandinavian Donations and Transfusions Database (SCANDAT2), which includes data on all blood donations and transfusions in Sweden and Denmark since the 1960s. Incident cases of hematologic malignancies were identified in the Swedish Cancer Register between 2000 and 2010. Cases were divided into nine patient groups based on diagnosis. RESULTS: A total of 28,693 patients were included in the cohort. Overall, the transfusion pattern varied depending on diagnosis and age. Patients with aggressive and acute diagnoses generally received more transfusions with immediate decline in transfusion incidence after diagnosis, whereas chronic diagnoses generally maintained more stable, but lower, transfusion incidence. In general, patients with leukemia received more transfusions than patients with lymphoma, and patients with acute leukemia as well as patients that had undergone allogeneic stem cell transplantations received the most transfusions. Within 2 years after diagnosis, patients with acute myeloid leukemia diagnosed at ages 0 to 65 years received on average between 30 to 40 red blood cell transfusions and platelet transfusions, respectively, corresponding to direct material costs close to 200,000 SEK (23,809 USD). CONCLUSION: Results from this population-based overview of blood use in hematologic malignancies showed high variability depending on diagnosis and age.

Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment.

BACKGROUND: A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery. OBJECTIVE: To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF). METHOD: ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s-1, representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150mg BID. RESULTS: Median plasma dabigatran concentrations at trough were 86ng/mL (29-150) and post-dose (2.8h after ingestion) 175ng/mL (67-490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (r=0.92, p<0.01) and Fib-tem (r=0.93, p<0.01), while with In-tem and low TF the correlation was weaker (r=0.72 and r=0.36, p<0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables (r-values 0.39-0.41, p<0.01), aPTT (r=0.70, p<0.01) and PT-INR (r=0.43, p<0.01) respectively. CONCLUSIONS: ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study.

Epidemiology of Massive Transfusion: A Binational Study From Sweden and Denmark.

OBJECTIVE: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. DESIGN: Descriptive cohort study. SETTING: Nationwide study with data from Sweden and Denmark. PATIENTS: The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. CONCLUSIONS: This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.

The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood safety resource with added versatility.

BACKGROUND: Risks of transfusion-transmitted disease are currently at a record low in the developed world. Still, available methods for blood surveillance might not be sufficient to detect transmission of diseases with unknown etiologies or with very long incubation periods. STUDY DESIGN AND METHODS: We have previously created the anonymized Scandinavian Donations and Transfusions (SCANDAT) database, containing data on blood donors, blood transfusions, and transfused patients, with complete follow-up of donors and patients for a range of health outcomes. Here we describe the re-creation of SCANDAT with updated, identifiable data. We collected computerized data on blood donations and transfusions from blood banks covering all of Sweden and Denmark. After data cleaning, two structurally identical databases were created and the entire database was linked with nationwide health outcomes registers to attain complete follow-up for up to 47 years regarding hospital care, cancer, and death. RESULTS: After removal of erroneous records, the database contained 25,523,334 donation records, 21,318,794 transfusion records, and 3,692,653 unique persons with valid identification, presently followed over 40 million person-years, with possibility for future extension. Data quality is generally high with 96% of all transfusions being traceable to their respective donation(s) and a very high (>97%) concordance with official statistics on annual number of blood donations and transfusions. CONCLUSIONS: It is possible to create a binational, nationwide database with almost 50 years of follow-up of blood donors and transfused patients for a range of health outcomes. We aim to use this database for further studies of donor health, transfusion-associated risks, and transfusion-transmitted disease.

Random aggregates in newly produced platelet units are associated with platelet activation and release of the immunomodulatory factors sCD40L and RANTES.

BACKGROUND: In connection with platelet (PLT) production, random but transient aggregates sometimes form in the newly produced units. The underlying mechanisms as well as the impact on cellular level of this phenomenon are unknown. Hypothetically, random occurrence of aggregates may induce biochemical changes leading to PLT activation and release of immunomodulatory factors from the PLTs. STUDY DESIGN AND METHODS: PLTs were aliquoted and prepared with an automated system for PLT pooling (OrbiSac, Terumo BCT) for a three-arm nonpaired study design (n=8). Initially aggregated PLT units in SSP+ were selected by visual inspection and compared to unaffected PLT units stored in SSP+ or 100% plasma. Cellular, metabolic, and functional variables were analyzed, including the concentrations of RANTES, sCD40L, and sTWEAK in the bags during a 9-day storage period. RESULTS: Isolated aggregated PLTs show signs of spontaneous activation and respond less efficiently to TRAP stimulation. RANTES, sCD40L, and sTWEAK accumulated in the various PLT units during storage but sCD40L and RANTES accumulated in the initially aggregated PLT units to higher concentrations than the reference units and PLTs stored in 100% plasma (p<0.001). Over time, the levels of sTWEAK increased more in the plasma storage environment compared with PLT units stored in SSP+ (p<0.001). CONCLUSION: Our data indicate that random occurrence of aggregates may lead to higher activation level and increased release of immunomodulatory factors from the PLTs.

Analysis of donor and recipient ABO incompatibility and antibody-associated complications after allogeneic stem cell transplantation with reduced-intensity conditioning.

Allogeneic hematopoietic stem cell transplantation (HSCT) can be performed across the ABO blood group barrier. The impact of ABO incompatibility on clinical outcome is controversial. A retrospective analysis of 310 patients who underwent HSCT with reduced-intensity conditioning between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-RBC antibodies in passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or recurring recipient type ABO antibodies (PRABO) after major ABO mm HSCT, and autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical outcome were analyzed by univariate and multivariate analysis for groups with or without anti-RBC antibodies. ABO blood group incompatibility did not affect clinical outcome despite an increased requirement of blood transfusion. Twelve patients with AIHA, 6 patients with PLS, and 12 patients with PRABO post-HSCT were identified. AIHA did not affect overall survival (OS) or transplant-related mortality (TRM), but patients with AIHA had a lower incidence of grades II to IV acute graft-versus-host disease (P = .05). OS in the PLS group was 0% compared with 61% in the whole group receiving minor ABO mm transplants (P < .001). Comparing PRABO patients with those receiving a major ABO mm HSCT, the OS was 17% versus 73% (P = .002) and TRM was 50% versus 21% (P = .03). At our center, PLS after minor ABO mm and PRABO antibodies after major ABO mm HSCT are significant risk factors for decreased OS and TRM. Our results suggest that occurrence of unexpected ABO antibodies after HSCT warrant a wider investigation individual to find the underlying cause.

Thromboelastography (TEG®) compared to conventional coagulation tests in surgical patients--a laboratory evaluation.

BACKGROUND: Several methods exist for evaluation of hypocoagulation in patients with perioperative bleeding, e.g. thromboelastography (TEG(®)) and conventional methods (platelet count, aPTT, INR and fibrinogen). Considering the vast experience of conventional methods it is important to investigate how well the methods correspond. METHODS: Sixty surgical patients were included prospectively and blood samples were taken perioperatively. TEG(®) and conventional parameters were analyzed simultaneously. An assessment of coagulopathy, based on a synthesis of the conventional methods, was done by two experienced coagulation specialists, blinded from the results of TEG(®) and from the results of each other. Hypocoagulation, defined by TEG(®) parameters; reaction time (R-time), angle, maximal amplitude (MA) and fibrinolysis, was evaluated according to a commonly used algorithm. RESULTS: To detect a platelet count below 150 × 10(9) L(-1), the sensitivity of TEG was 17% (95% CI, 7-36%) with angle and 25% (95% CI, 11-45%) with MA. The sensitivity to detect fibrinogen below 2 g/L was 11% (95% CI, 3-29%) with angle and 21% with MA (95% CI, 8-43%). To detect aPTT more than 40 s and INR more than 1.2 with R-time, the sensitivity was 19% (95% CI, 8-37%) and 0% (95% CI, 0-69%) respectively. The agreement of the evaluator's assessments of hypocoagulation was 100%, but the agreement with the overall TEG(®) analysis was poor with a sensitivity of 33% and a specificity of 95%. CONCLUSION: The agreement between conventional laboratory tests and TEG is poor, but it remains uncertain which type of coagulation tests that best reflects the actual bleeding risk.

Noninvasive single-exon fetal RHD determination in a routine screening program in early pregnancy.

OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: I.

Constructing a population-based research database from routine maternal screening records: a resource for studying alloimmunization in pregnant women.

BACKGROUND: Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues. STUDY DESIGN AND METHODS: Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays. RESULTS: More than one million (1,191,761) births with valid screening information from 1982-2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time. CONCLUSION: This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions, such as the etiological significance of non-anti-D antibodies.