scholarly journals RhD Immunization Despite Adequate Immunoprophylaxis: Role of Fc Gamma Receptor Gene Polymorphisms

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 759-759
Author(s):  
Tamara C Stegmann ◽  
Sietse Q Nagelkerke ◽  
Dian van Winkelhorst ◽  
Taco W Kuijpers ◽  
Gestur Vidarsson ◽  
...  

Abstract Introduction: One of the most effective immunological interventions in clinical medicine is the prevention of hemolytic disease of the newborn by prophylactic Rh immune globulin (Rh-Ig) therapy. The administration of ante- and postnatal Rh-Ig has reduced the risk of RhD immunization in the Netherlands from 17% to a mere 0.31%, yet its mechanism of action is still unknown. To gain more insight into the possible working mechanism of the Rh-Ig prophylaxis we analyzed potential risk factors and genotyped all known IgG-Fc receptor (protein FcγR, gene FCGR) variants known to date, on a cohort of Dutch women who failed Rh-Ig prophylaxis and developed anti-D antibodies. Adequate Rh-Ig immunoprophylaxis was defined as an antenatal and postnatal prophylaxis of 1,000 IU (200 µg) in both current and previous pregnancies, according to the Dutch guidelines. Material and Methods: Between 1999 and 2013 we identified 274 women who produced anti-D antibodies. Through a structured questionnaire we collected information about Rh-Ig prophylaxis and additional clinical data for potential risk factors. In 122 cases, adequate Rh-Ig prophylaxis was given, and clinical risk factors for fetal maternal hemorrhage (FMH) could be collected. Their clinical circumstances were compared to a control group of 339 randomly selected pregnant women. The Rh-Ig therapy failure of 57 of those women could not be explained through our risk factor analysis. From these 57 cases, DNA was obtained, and used for the FcγR-specific multiplex ligation-dependent probe amplification (MLPA) assay, identifying both single nucleotide polymorphisms and copy number variations in the FCGR locus. The results were compared to a control group of 200 healthy donors. Results: A history of red blood cell transfusion (p=0.05) and caesarean section (p<0.0001) were identified to be independent risk factors for RhD immunization. All other described risk factors for FMH such as miscarriage, termination of pregnancy, or invasive diagnostic procedures, requiring an additional Rh-Ig dose according to the guidelines, were not found to increase the risk of immunoprophylaxis failure. RhD-immunization due to caesarian section or red blood cell transfusion accounted for 53% of our cohort, suggesting an alternative explanation for the production of Rh-Ig alloantibodies in the remaining 47% of the cases - despite adequate amount of prophylaxis given in current and previous pregnancies. We therefore postulate the existence of a genetic variation that puts women at increased risk for RhD immunization during pregnancy. To test this hypothesis we analyzed the genetic variation in the FCGR locus and found a significantly (p=0.02) increased prevalence of the FCGR2 -ORF, expressing a functional copy of the activating FcγRIIc, which is otherwise a pseudogene. Strikingly, the prevalence of the 2B.4-promotor haplotype of the FCGR2B gene, associated with a 1.5 fold increase of the inhibitory FcγRIIb, was strongly (p=0.0001) increased. Conclusion: Caesarian section and red blood cell transfusion are risk factors that increase RhD immunization during pregnancies, accounting for about half failed Rh-Ig prophylactic cases. Genetic variation in the FCGR-gene might be a possible explanation for increased immunization risk. In our cohort we encountered a significantly increased frequency of individuals expressing FcγRIIc, along with a polymorphism encoding for a higher expression of the inhibitory receptor FcγRIIb, suggesting these genes to influence immune responses to RBC in a manner previously unrecognized. Disclosures No relevant conflicts of interest to declare.

2020 ◽  
Vol 34 ◽  
pp. 205873842096381
Author(s):  
Zheng-Li Wang ◽  
Yao An ◽  
Yu He ◽  
Xiao-Yu Hu ◽  
Lu Guo ◽  
...  

Sepsis, a severe infectious disease in the neonatal period, is considered a risk factor for necrotizing enterocolitis (NEC). To investigate the specific risk factors for NEC in septic infants, septic infants admitted to our center from January 2010 to April 2018 were included. Septic neonates with proven NEC (Bell’s stage ⩾II) were enrolled in the NEC group, and those without NEC were enrolled in the control group. Demographics, clinical characteristics, and risk factors were compared between the two groups. Univariate and logistic regression analyses were used to evaluate the potential risk factors for NEC. A total of 610 septic neonates were included, of whom 78 (12.8%) had complicated NEC. The univariate analysis indicated that infants with NEC had a lower birth weight, a lower gestational age, and older age on admission than those without NEC ( P < 0.05). Higher rates of anemia, prolonged rupture of membranes (PROM) (⩾18 h), pregnancy-induced hypertension, late-onset sepsis (LOS), red blood cell transfusion and hypoalbuminemia were observed in the NEC group than in the non-NEC group (P<0.05). Logistic regression analysis revealed LOS ( P = 0.000), red blood cell transfusion ( P = 0.001) and hypoalbuminemia ( P = 0.001) were associated with the development of NEC. Among NEC infants, those who needed red blood cell transfusion had a longer hospitalization duration than those who did not need transfusion ( P < 0.05). LOS, red blood cell transfusion and hypoalbuminemia were independent risk factors for the development of NEC in infants with sepsis. Taking measures to reduce the occurrence of hypoproteinemia and severe anemia may help to reduce the occurrence of NEC in septic neonates.


2021 ◽  
Vol 10 (11) ◽  
pp. 2462
Author(s):  
Barbara Ruaro ◽  
Paola Confalonieri ◽  
Mario Santagiuliana ◽  
Barbara Wade ◽  
Elisa Baratella ◽  
...  

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females; mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females; mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females; mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p > 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment.


2020 ◽  
Vol 139 ◽  
pp. e308-e315 ◽  
Author(s):  
Rafael De la Garza Ramos ◽  
Yaroslav Gelfand ◽  
Joshua A. Benton ◽  
Michael Longo ◽  
Murray Echt ◽  
...  

2019 ◽  
Vol 37 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Andrew-Paul Deeb ◽  
Christopher T. Aquina ◽  
John R.T. Monson ◽  
Neil Blumberg ◽  
Adan Z. Becerra ◽  
...  

Background/Aims: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). Methods: In a retrospective study, patients with stage I–III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. Results: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24–7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94–7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12–4.48). Conclusion: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.


2010 ◽  
Vol 24 (3) ◽  
pp. 413-417 ◽  
Author(s):  
Albert H.M. van Straten ◽  
Suzanne Kats ◽  
Margreet W.A. Bekker ◽  
Frank Verstappen ◽  
Joost F.J. ter Woorst ◽  
...  

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S564-S564
Author(s):  
S García Mateo ◽  
S J Martínez-Domínguez ◽  
M C Aso Gonzalvo ◽  
C J Gargallo-Puyuelo ◽  
B Gallego Llera ◽  
...  

Abstract Background Patients with Inflammatory Bowel Disease (IBD) suffer from a chronic illness and many of them need immunosuppressive therapy throughout the course of the disease. Consequently, COVID-19 pandemic has caused uncertainty about the possible increased risk of suffering SARS-CoV-2 infection that could confer IBD or its treatments. The aim of this study is to assess SARS-CoV-2 seroprevalence in patients with IBD as well as the existence of potential risk factors for its development. Methods This is a unicentric cross-sectional study developed in IBD unit of University Hospital “Lozano Blesa” of Zaragoza. Patients older than 18 years with established diagnosis of Crohn′s Disease (CD), Ulcerative Colitis (UC) or Indeterminate Colitis (IC) have been included. A blood sample has been drawn from each patient to detect IgG against SARS-CoV-2 (ELISA method) and each patient has completed a questionnaire to know symptoms related to infection and previous comorbidity. We have performed a descriptive analysis and a univariate analysis to study relationship between potential risk factors and seroconversion against SARS-CoV-2. Results 431 patients have been included, with a mean age of 50.2 ± 14.1 years and a 51.3% of women. Of them, 49.7% suffer from UC, 49.2% CD and 1.2% IC. Related to the treatment, 23.5% receive anti-TNF biologic agents, 13.1% other kind of biologic agents, 9.3% immunomodulators, 7.7% combined treatment (biologic agent and immunomodulator), 33.1% other treatment and 13.3% no treatment. According to World Health Organization (WHO) definitions, 85.6% had not suffered the infection, 7.7% were confirmed cases (only 3 admitted patients) and 6.7% were probable cases. The seroprevalence of SARS-CoV-2 obtained is 8.8%, being significantly higher among confirmed cases than among probable cases (71.0% in confirmed vs 6.9% in probable; RR 10.3; p&lt;0.001). A higher risk of seroconversion has been detected among patients without biologic agents (11.8% in patients without biologic agents vs 5.3% in patients with biologic agents; RR 2.2; p=0.021). No differences have been observed in the seroprevalence of patients with other treatments for IBD or in terms of age, active smoking, level of inflammation markers, the presence of symptoms of infection or hospital admission. Conclusion The seroprevalence of SARS-CoV-2 of Aragon′s patients with IBD is similar to that described in national seroprevalence study of Ministry of Health for the region (8.8%). The treatment with biologic agents is associated with a lower risk of seroconversion


Author(s):  
Talko Bernhard Dijkhuis ◽  
Ruby Otter ◽  
Marco Aiello ◽  
Hugo Velthuijsen ◽  
Koen Lemmink

AbstractInjuries of runners reduce the ability to train and hinder competing. Literature shows that the relation between potential risk factors and injuries are not definitive, limited, and inconsistent. In team sports, workload derivatives were identified as risk factors. However, there is an absence of literature in running on workload derivatives. This study used the workload derivatives acute workload, chronic workload, and acute: chronic workload ratios to investigate the relation between workload and injury risk in running. Twenty-three competitive runners kept a daily training log for 24 months. The runners reported training duration, training intensity and injuries. One-week (acute) and 4-week (chronic) workloads were calculated as the average of training duration multiplied by training intensity. The acute:chronic workload ratio was determined dividing the acute and chronic workloads. Results show that a fortnightly low increase of the acute:chronic workload ratio (0.10–0.78) led to an increased risk of sustaining an injury (p<0.001). Besides, a low increase of the acute:chronic workload ratio (0.05–0.62) between the second week and third week before an injury showed an association with increased injury risk (p=0.013). These findings demonstrate that the acute:chronic workload ratio relates to injury risk.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chen Wang ◽  
Isabelle Le Ray ◽  
Brian Lee ◽  
Agneta Wikman ◽  
Marie Reilly

Abstract The increased risk of venous thromboembolism (VTE) associated with pregnancy is well-known and prophylaxis guidelines consider a number of risk factors. Although non-O blood group and red blood cell (RBC) transfusion are known to be associated with VTE risk, their contribution to pregnancy-associated VTE has received little attention. This study was conducted in a population-based cohort of 1,000,997 deliveries to women with no prior history of VTE or thrombophilia. The independent contributions of ABO blood type and RBC transfusion to the risks of antepartum, peripartum and postpartum VTE are reported as odds ratios adjusted for risk factors that are considered in current prophylaxis guidelines and other potential confounders. Compared with type O, A and B blood types have higher risk of antepartum and postpartum VTE, with odds ratios between 1.4 and 1.8. Transfusion around delivery has the largest increased risks and a dose-response effect, with adjusted odds ratios from 2.60 (1.71–3.97) for 1–2 units to 3.55 (1.32–9.55) for more than 5 units. ABO blood type and RBC transfusion were found to be independent risk factors for pregnancy-associated VTE. Further research is required to understand the underlying mechanisms and to conduct a risk-benefit assessment of the small volumes of RBCs transfused around delivery.


2021 ◽  
pp. 175857322098225
Author(s):  
Kyle J Kopechek ◽  
Travis L Frantz ◽  
Joshua S Everhart ◽  
Richard Samade ◽  
Julie Y Bishop ◽  
...  

Purpose To identify the effect of surgical indication, patient factors, and perioperative characteristics on transfusion after shoulder arthroplasty (SA). Methods Shoulder arthroplasties for osteoarthritis (OA) ( N = 47), rotator cuff arthropathy (RCA) ( N = 50), fracture ( N = 76), revision ( N = 66), and periprosthetic joint infection (PJI) ( N = 35) performed at a single institution during a 6-year period were included. All other indications were excluded. Patient-based and surgical risk factors, including surgical indication, for postoperative allogeneic red blood cell transfusion were assessed with multivariate logistic regression analysis. Results A total of 274 SAs were included; transfusions were performed in 2% (2/97) of primary SAs for OA or RCA. Increased transfusion rates occurred in PJI (23%, p = 0.0006) and fracture (18%, p = 0.0018) cases. The mean preoperative hemoglobin (Hgb) was 12.2 ± 2.2 with PJI, 12.0 ± 2.1 with fracture, and 13.3 ± 1.6 g/dL for all other SAs. Independent risk factors for transfusion included lower preoperative hemoglobin ( p < 0.001), PJI indication ( p = 0.008), and fracture indication ( p = 0.02), with no difference for fracture greater or less than 4 weeks old ( p = 0.53). Conclusion Risk factors for allogeneic red blood cell transfusion after SA were low preoperative hemoglobin and procedures for PJI or fracture. Level of Evidence: Level III, retrospective case-control study


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