| 1. |
- Auvinen, Marja-Kaisa, et al.
(author)
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Patterns of blood use in Sweden from 2008 to 2017: A nationwide cohort study
- 2020
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In: Transfusion. - : WILEY. - 0041-1132 .- 1537-2995. ; 60:11, s. 2529-2536
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Edgren, Gustaf, et al.
(author)
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Improving health profile of blood donors as a consequence of transfusion safety efforts
- 2007
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In: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 47:11, s. 2017-2024
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Journal article (peer-reviewed)abstract
- Background: Transfusion safety rests heavily on the health of blood donors. Although they are perceived as being healthier than average, little is known about their long-term disease patterns and to which extent the blood banks' continuous efforts to optimize donor selection has resulted in improvements. Mortality and cancer incidence among blood donors in Sweden and Denmark was investigated. Study Design and Methods: All computerized blood bank databases were compiled into one database, which was linked to national population and health data registers. With a retrospective cohort study design, 1,110,329 blood donors were followed for up to 35 years from first computer-registered blood donation to death, emigration, or December 31, 2002. Standardized mortality and incidence ratios expressed relative risk of death and cancer comparing blood donors to the general population. Results: Blood donors had an overall mortality 30 percent lower (99% confidence interval [CI] 29%-31%) and cancer incidence 4 percent lower (99% CI 2%-5%) than the background population. Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation. Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier. Conclusion: Blood donors enjoy better than average health. Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the selection of a particularly healthy subpopulation.
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| 3. |
- Clausen, Frederik Banch, et al.
(author)
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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
- 2022
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In: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
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Research review (peer-reviewed)abstract
- 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.
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| 4. |
- Dahl, Viktor, et al.
(author)
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Transmission of viral hepatitis through blood transfusion in Sweden, 1968 to 2012
- 2020
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In: Eurosurveillance. - : European Centre for Disease Control and Prevention (ECDC). - 1025-496X .- 1560-7917. ; 25:29, s. 7-15
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Journal article (peer-reviewed)abstract
- Introduction: Viral hepatitis remains a significant threat to transfusion safety, although largely mitigated by donor screening. Aim: Our 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). Method: We 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. Results: Among 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. Conclusion: There 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.
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| 5. |
- Edgren, Gustaf, et al.
(author)
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The new Scandinavian Donations and Transfusions database (SCANDAT2) : a blood safety resource with added versatility
- 2015
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In: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 55:7, s. 1600-1606
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Journal article (peer-reviewed)abstract
- BackgroundRisks 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 MethodsWe 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. ResultsAfter 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. ConclusionsIt 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.
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| 6. |
- Edgren, Gustaf, et al.
(author)
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Transmission of Neurodegenerative Disorders Through Blood Transfusion A Cohort Study
- 2016
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In: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 165:5, s. 316-
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Journal article (peer-reviewed)abstract
- Background: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications. Objective: To investigate possible transfusion transmission of neurodegenerative disorders. Design: Retrospective cohort study. Setting: Nationwide registers of transfusions in Sweden and Denmark. Participants: 1 465 845 patients who received transfusions between 1968 and 2012. Measurements: Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. Results: Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening. Limitation: Observational study design, underascertainment of the outcome, and possible insufficient statistical power. Conclusion: The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare.
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| 7. |
- Geisen, Christof, et al.
(author)
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An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia : a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study
- 2023
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 21:4, s. 838-849
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Journal article (peer-reviewed)abstract
- Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a–negative participants as compared with placebo. Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2–negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse events were possibly related to treatment, both in RLYB211–treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. Conclusion: These data support the hypothesis that anti–HPA-1a could be used as prophylaxis in women at risk of having an FNAIT–affected pregnancy.
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| 8. |
- Halmin, Marit, et al.
(author)
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Epidemiology of Massive Transfusion : A Binational Study From Sweden and Denmark
- 2016
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 44:3, s. 468-477
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Halmin, Märit, et al.
(author)
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Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion : A Binational Cohort Study
- 2017
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In: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:4, s. 248-256
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Journal article (peer-reviewed)abstract
- Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists.Objective: To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects.Design: Binational cohort study.Setting: All transfusion recipients in Sweden and Denmark. Patients: 854 862 adult patients who received transfusions from 2003 to 2012.Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression.Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was -0.2% (95% CI, -0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units.Limitation: Observational study; risk of confounding by indication.Conclusion: Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed.
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| 10. |
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| 11. |
- Kjellberg, Gunilla, et al.
(author)
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Platelet function analysed by ROTEM platelet in cardiac surgery after cardiopulmonary bypass and platelet transfusion
- 2020
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In: Transfusion Medicine. - : Wiley. - 0958-7578 .- 1365-3148. ; 30:5, s. 369-376
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Journal article (peer-reviewed)abstract
- 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.
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| 12. |
- Refsum, Erle, et al.
(author)
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Intracranial hemorrhages in neonates born from 32 weeks of gestation - low frequency of associated fetal and neonatal alloimmune thrombocytopenia : a register-based study
- 2018
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In: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 58:1, s. 223-231
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Journal article (peer-reviewed)abstract
- BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH.STUDY DESIGN AND METHODS: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records.RESULTS: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 109/L.CONCLUSIONS: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.
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| 13. |
- Remberger, Mats, et al.
(author)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Journal article (peer-reviewed)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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| 14. |
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| 15. |
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| 16. |
- Tynngård, Nahreen, 1976-, et al.
(author)
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Cryopreservation of buffy coat derived platelets: Paired in vitro characterization using uncontrolled versus controlled freezing rate protocols
- 2021
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In: Transfusion. - : WILEY. - 0041-1132 .- 1537-2995. ; 61:2, s. 546-556
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Journal article (peer-reviewed)abstract
- 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, Delta psi, 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.
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| 17. |
- Tynngård, Nahreen, 1976-, et al.
(author)
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Haemostatic responsiveness and release of biological response modifiers following cryopreservation of platelets treated with amotosalen and ultraviolet A light
- 2020
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In: Blood Transfusion. - : SIMTIPRO SRL. - 1723-2007. ; 18:3, s. 191-199
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Journal article (peer-reviewed)abstract
- Background - Due to the risk of replication of contaminating pathogens, platelets have a limited storage time of 5 days, which can be prolonged to 7 days by the use of pathogen inactivation technologies. Cryopreservation (CP) may be an alternative to permit longer storage periods and increased availability. However, the preparation of platelets can result in secretion of biological response modifiers (BRM), which can cause adverse transfusion reactions in the recipient. We investigated the impact of CP on platelet function and release of BRM in untreated (conventional) and pathogen-inactivated (PI) platelet concentrates. Materials and methods - Twelve buffy coat-derived platelet units were treated with amotosalen and ultraviolet A light to inactivate pathogens. Twelve untreated units were used as controls. The 24 units were cryopreserved and in vitro variables were analysed before and after CP. The in vitro variables investigated included platelet surface receptors and activation markers by flow cytometry, and coagulation time by viscoelastography. A panel of BRM, including cytokines, was investigated. Results - CP of both conventional and PI platelets resulted in a significant increase of BRM with similar increases of most of the BRM after CP of conventional and PI platelet concentrates. The increase in some of the BRM correlated significantly with shortened coagulation time, increased P-selectin expression, reduced mitochondrial transmembrane potential, and reduced capacity to respond to stimulation with ADP and collagen. Discussion - Cryopreservation of both conventional and PI platelets results in secretion of BRM. The increase in some of the BRM correlated with changes in platelet function variables and suggests that BRM release is affected, in part, in a similar way by CP as are changes in platelet function variables. PI with amotosalen and ultraviolet A light in combination with CP did not affect the release of immunomodulatory factors more than CP alone did.
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| 18. |
- Viirman, Frida
(author)
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Mother, how are you? : Studies on self-rated health and childbirth experience
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Pregnancy and childbirth are characterised by emotional and physical changes, which can affect the mother’s mental health postpartum, as well as the infant. One step towards alleviating adverse consequences is to measure health status and childbirth experience. The aim of this thesis was to investigate women’s subjective health prior to pregnancy in relation to infant birth outcomes and childbirth experience, and to explore childbirth experience and its measurement from different perspectives.The thesis consists of four papers, of which the first two were based on data from the Swedish Pregnancy Register 2013-2018. In Paper I, self-rated health (SRH) prior to pregnancy was explored in relation to adverse birth outcomes, while Paper II investigated risk factors for negative childbirth experience. In Paper III, 112 written descriptions of negative childbirth experience were qualitatively explored in relation to events during labour and birth. In Paper IV, a single-item question about overall childbirth experience was compared to the validated four-dimensional Childbirth Experience Questionnaire 2, completed by 2,953 women.Overall, the prevalence of poor SRH prior to pregnancy was 9.9%. Among primiparas, 8.5% reported poor SRH, and 8.4% negative childbirth experience. Poor SRH was independently associated with small for gestational age, preterm birth, and negative childbirth experience. It was also associated with stillbirth, but not after adjustment for other risk factors. The main contributing factors to negative childbirth experience were related to labour and birth, with operative birth modes being the most prominent. Poor SRH was the only pre-gestational factor independently associated with negative childbirth experience. Only small differences between type of negative childbirth experience, in terms of qualitative sub-themes, were found between birth modes and complications during labour. Fear-based emotions was the most common sub-theme. The single-item measurement of overall childbirth experience mainly captured experiences of perceived safety, to a lesser extent own capacity and participation, but not experiences related to professional support.In conclusion, findings show the potential of using SRH assessments clinically to identify women in need of more extensive attention during pregnancy and childbirth. This thesis provides further proof of negative childbirth experience being multidimensional and subjective, and dominated by fear. When using single-item ratings of childbirth experience clinically, one must be aware that experiences of support are not well represented.
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| 19. |
- Viirman, Frida, et al.
(author)
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Negative childbirth experience in relation to mode of birth and events during labour: a mixed method study
- 2023
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In: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier. - 0301-2115 .- 1872-7654. ; 282, s. 146-154
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Journal article (peer-reviewed)abstract
- Objective: To explore descriptions of negative childbirth experience in relation to mode of birth and events during labour.Design: A descriptive study using a convergent mixed methods design. Written responses to open-ended online questions regarding negative childbirth experience were explored using qualitative content analysis. Generated sub-themes were quantified, and stratified on mode of birth and events during labour.Participants and setting: 112 women with low ratings of overall childbirth experience, participating in a randomised controlled trial evaluating internet-based cognitive behavioural therapy in Sweden. Qualitative data were collected before randomisation, three months postpartum.Results: Four sub-themes emerged from the qualitative analysis: Experiencing fear-based emotions, Experiencing physical distress, Being affected by caregivers’ and partner’s behaviour and Being affected by bad facilities and poor organisation. Only small differences were found when stratifying sub-themes on mode of birth and events during labour. Regardless of mode of birth and events during labour, the childbirth experience was dominated by fear-based emotions.Key conclusions and implications for practice: Mixed-methods analyses demonstrate the challenges in understanding negative childbirth experience in relation to mode of birth and specific events during labour, with results clearly showing the multifaceted nature of this concept. The central role of fear in relation to negative childbirth experience should be considered when designing support during and after labour, to prevent adverse effects of the childbirth experience.
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| 20. |
- Viirman, Frida, et al.
(author)
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Negative childbirth experience-what matters most? : a register-based study of risk factors in three time periods during pregnancy
- 2022
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In: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 34
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Journal article (peer-reviewed)abstract
- Objective: To explore the impact of risk factors representing three different time periods during pregnancy on negative childbirth experience.Methods: This was a register-based cohort study of 80 482 primiparas giving birth to singleton, term infants in Sweden 2013-2018, elective caesarean sections (CS) excluded. Hierarchical logistic regression was performed to calculate adjusted odds ratios (aOR) with 95% confidence intervals (CIs) in three blocks, each representing risk factors from one of three time periods: I) before pregnancy, II) pregnancy, III) childbirth.Results: Of the pre-gestational factors, only poor self-rated health (SRH) remained associated with negative childbirth experience after adjustment for pregnancy- and childbirth-related factors (aOR 1.20, 95% CI 1.08-1.34). Psychiatric care during pregnancy and fear of childbirth were both associated with negative birth experience (aOR 1.51, 95% CI 1.35-1.69; aOR 1.50, 95% CI 1.32-1.70), as were all childbirth-related factors included in the model. Women giving birth operatively vaginally or by unplanned CS under regional anaesthesia had three-fold higher ORs for rating their overall childbirth experience as negative (aOR 3.29, 95% CI 3.04-3.57; aOR 3.07, 95% CI 2.80-3.38). The highest OR, 5.44, was seen among women undergoing unplanned CS under general anaesthesia (95% CI 4.55-6.50).Conclusion: The main contributing factors to negative childbirth experience are related to labour and birth, but poor SRH prior to pregnancy, together with psychiatric care during pregnancy and fear of childbirth, place the woman in a vulnerable position, and require extra attention.
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| 21. |
- Viirman, Frida, et al.
(author)
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Overall childbirth experience : what does it mean? A comparison between an overall childbirth experience rating and the Childbirth Experience Questionnaire 2
- 2023
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In: BMC Pregnancy and Childbirth. - : BioMed Central (BMC). - 1471-2393 .- 1471-2393. ; 23
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Journal article (peer-reviewed)abstract
- Background: In clinical settings and research studies, childbirth experience is often measured by the use of a single-item question about overall experience. Little is known about what women include in this rating, which complicates the design of adequate follow-up, as well as the interpretation of research findings based on ratings of overall childbirth experience. The aim of this study was to examine which known dimensions of childbirth experience women include in the rating on a single-item measure.Methods: Ratings of overall childbirth experience on a 10-point numeric rating scale (NRS) from 2953 women with spontaneous or induced onset of labour at two Swedish hospitals were evaluated against the validated Childbirth Experience Questionnaire 2 (CEQ2), completed on one of the first days postpartum. The CEQ2 measures four childbirth experience domains: own capacity, perceived safety, professional support and participation. Internal consistency for CEQ2 was evaluated by calculating Cronbach’s alpha. NRS ratings were explored in relation to CEQ2 using empirical cumulative distribution function graphs, where childbirth experience was defined as negative (NRS ratings 1–4), mixed (NRS ratings 5–6) or positive (NRS ratings 7–10). A multiple linear regression analysis, presented as beta coefficients (B) and 95% confidence intervals (CI), was also performed to explore the relationship between the four domains of the CEQ2 and overall childbirth experience.Results: The prevalence of negative childbirth experience was 6.3%. All CEQ2-subscales reached high or acceptable reliability (Cronbach’s alpha = 0.78; 0.81; 0.69 and 0.66, respectively). Regardless of overall childbirth experience, the majority of respondents scored high on the CEQ2 subscale representing professional support. Overall childbirth experience was mainly explained by perceived safety (B = 1.60, CI 1.48–1.73), followed by own capacity (B = 0.65, CI 0.53–0.77) and participation (B = 0.43, CI 0.29–0.56).Conclusions: In conclusion, overall childbirth experience rated by a single-item measurement appears to mainly capture experiences of perceived safety, and to a lesser extent own capacity and participation, but appears not to reflect professional support. CEQ2 shows good psychometric properties for use shortly after childbirth, and among women with induced onset of labour, which increases the usability of the instrument.
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| 22. |
- Viirman, Frida, et al.
(author)
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Self‐rated health before pregnancy and adverse birth outcomes in Sweden : A population‐based register study
- 2021
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In: Birth. - : John Wiley & Sons. - 0730-7659 .- 1523-536X. ; 48:4, s. 541-549
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Journal article (peer-reviewed)abstract
- Background Poor self-rated health (SRH) at time of childbirth has been associated with adverse birth outcomes. However, it is not known whether prepregnancy SRH contributes to these outcomes or whether SRH is a proxy for some other factors. Therefore, the purpose of this study was to explore the associations between poor SRH before pregnancy and adverse birth outcomes. In addition, maternal characteristics associated with SRH before pregnancy were explored.Methods A population-based register study encompassing 261 731 deliveries in Sweden between January 2013 and July 2017 was conducted. The associations between poor SRH before pregnancy, rated at first antenatal visit, and the adverse birth outcomes of stillbirth, small for gestational age (SGA), and preterm birth were investigated with logistic regression analyses and presented as crude (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI).Results Poor SRH before pregnancy was largely characterized by a history of psychiatric care and was associated with stillbirth (OR 1.37, 95% CI 1.04-1.79), SGA birth (OR 1.29, 95% CI 1.19-1.39), and preterm birth (OR 1.41, 95% CI 1.32-1.50). Adjusting for established risk factors for adverse birth outcomes, poor SRH remained associated with SGA birth (aOR 1.16, 95% CI 1.07-1.26) and preterm birth (aOR 1.25, 95% CI 1.17-1.33), but not with stillbirth (aOR 1.08, 95% CI 0.81-1.43).Conclusions SRH assessments could be used in early pregnancy to identify women in need of more extensive follow-up, as SRH appears to capture something beyond currently known risk factors for adverse birth outcomes.
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| 23. |
- Wikman, Agneta, et al.
(author)
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Blood components, special components and whole blood - what and to whom? : Blodkomponenter och helblod – så framställs och används de.
- 2021
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In: Läkartidningen. - 0023-7205. ; 118:11
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Journal article (peer-reviewed)abstract
- Sweden does not have a national blood authority and guidelines for blood transfusions are lacking, leading to varying routines of production and usage of blood in the different regions. The minimum quality requirements are defined in EU Directive 2002/98/EG and in the Swedish SOSFS 2009:28. The standard blood components are red blood cells, plasma and platelets, while special components such as irradiated, washed, frozen-thawed or antigen-matched products are prescribed on certain clinical indications. Thresholds for transfusion of red blood cells and platelets are discussed as well as indications for plasma transfusions. Further, there is evidence that early, balanced blood transfusions in massive bleeding reduce mortality, which has led to requests for blood products in prehospital settings.
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| 24. |
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| 25. |
- Wikman, Agneta Taune, et al.
(author)
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Noninvasive Single-Exon Fetal RHD Determination in a Routine Screening Program in Early Pregnancy.
- 2012
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In: Obstetrics and Gynecology. - 1873-233X. ; 120:2, s. 227-234
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Journal article (peer-reviewed)abstract
- 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.
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| 26. |
- Wikman, Agneta
(author)
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The role of granulocyte antibodies in monocyte and granulocyte activation
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Granulocytes and monocytes are important cells during the first phase of inflammation. They are activated and recruited from the blood vessels to inflammatory sites via the regulation of receptors involved in adhesion to endothelium. Through phagocytosis and the production of reactive oxygen metabolites and cytokines, they are crucial for the initiation of an immune response. Antibodies against surface and intracellularly expressed granulocyte antigens are important in a number of clinical conditions. Detection of anti neutrophil cytoplasmic antibodies (ANCA) is a diagnostic marker for systemic vasculitis and there is also increasing evidence for a pathophysiological role of the antibody. The objective of this thesis was to analyse the functional responses of granulocytes and monocytes to activation, with special attention paid to the relevance of granulocyte antibodies. In the first study the expression of receptors associated to adhesion to endothelium (CD62L and CD11b), binding of complement and immunoglobulin (CD35 and CD16) and the production of reactive oxygen metabolites were analysed on granulocytes after storage for different periods of time. Next we evaluated a flow cytometric method for the detection of granulocyte antibodies against surface and intracellular antigens. In the third study we determined the in vitro expression of CD62L and CD 11b and the production of reactive oxygen metabolites in monocytes in response to incubation with ANCA. Finally, in a prospective clinical study the monocyte activation and the concentration of soluble inflammation markers and soluble adhesion molecules were analysed in patients with acute anti-proteinase 3 (PR3) positive systemic vasculitis. In our first study we demonstrated a marked decrease in granulocyte CD62L expression concomitant with CD11b up-regulation at 24 hours storage. The expression of receptors associated with phagocytosis and the capacity to produce oxygen metabolites remained more stable. In the next study we showed that antibodies against granulocyte antigens can be detected by flow cytometry and by using both un-permeabilized and permebilized target cells, antibodies against surface and intracellularly expressed antigens can be distinguished. We found a decreased CD62L expression and enhanced production of oxygen radicals in monocytes upon in vitro ANCA stimulation. Compared to ANCA positive IgG-fractions, ANCA positive sera induced a more pronounced CD62L down-regulation, which supports the contribution of other soluble serum factors beside IgG. In contrast with our in vitro finding, monocytes from patients with acute ANCA-positive vasculitis showed reduced capacity to produce oxygen radicals. This may be a consequence of a prolonged period of immune activation and a more dynamic situation in vivo. High concentration of anti-PR3 correlated to decreased CD62L and increased CD11b expression on monocytes. Soluble inflammation markers (sCD14, IL-6, sTNFR1, IL-8, IL-10) as well as soluble adhesion molecules (sVCAM-1, sICAM-11) were enhanced compared to in healthy controls and similar compared to in a control group with acute ANCA-negative infection. The regulation of adhesion receptors is crucial in the initial attachment to the endothelium in an inflammatory response and a dysregulated CD62L/CD11b expression on monocytes may have pathophysiological implications for the endothelial damage seen in vasculitis.
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| 27. |
- Wikman Larhed, Agneta
(author)
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The mucus layer and other barriers to intestinal drug absorption
- 1997
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Doctoral thesis (other academic/artistic)abstract
- The extraepithelial mucus layer acts as a barrier to the absorption and diffusion of drugs. Three in vitro models have been used for studies of this and other intestinal barriers to drug transport. A drug absorption model based on monolayers of the mucus-producing human intestinal goblet HT29-H cell line was developed. The goblet cells produced mucin molecules and a mucus layer that covered the surface of the cells. The permeability of the gobletcell monolayers to the lipophilic molecule testosterone increased after removal of the mucus layer while the permeability to the small hydrophilic molecule mannitol was not altered.The mucus layer contributed 78% of the total resistance to absorption of testosterone in the HT29-H model, while the corresponding values for the unstirred water layer, the cell monolayer and the filter were 16%, 5% and 1%, respectively.A co-culture model containing absorptive Caco-2 cells and goblet HT29-H cells (the two most abundant epithelial cell types) was developed. A seeding density of 1% HT29-H cells resulted in co-cultures comprising 30% goblet cells in small clusters after 4 weeks in culture. Tight junctions were formed between the two cell types as revealed by electron microscopy and transepithelial electrical resistance measurements. The permeability of the monolayers tohydrophilic drugs increased with increasing numbers of goblet cells. The specific tight junction permeability, adjusted for junctional path length, was higher in HT29-H cells than Caco-2 cells.A relationship between the octanol/water distribution ratio and the self-diffusion coefficient of drugs was found in a native pig intestinal mucus model (PIM) but not in a purified pig gastric mucin model (PPGM), indicating that mucus components other than mucin molecules interact with drugs. PIM was thus found to be a more complete model of the barrier properties of gastrointestinal mucus than PPGM.The major components of PIM, other than water, were lipids and proteins; concentrations of mucin and DNA were lower. Of the individual components of native intestinal mucus, lipids were found to have the greatest influence on the diffusion of drugs.
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| 28. |
- Zhao, Jingcheng, et al.
(author)
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Blood use in hematologic malignancies : a nationwide overview in Sweden between 2000 and 2010
- 2018
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In: Transfusion. - : John Wiley & Sons. - 0041-1132 .- 1537-2995. ; 58:2, s. 390-401
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Journal article (peer-reviewed)abstract
- BACKGROUNDPatients 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 METHODSA 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. RESULTSA 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). CONCLUSIONResults from this population-based overview of blood use in hematologic malignancies showed high variability depending on diagnosis and age.
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