History Of Red Blood Cell Transfusion Research Articles

Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re-evaluation of transfusion practices in preterm infants.

Predictors of Red Blood Cell Transfusion in Elderly COVID-19 Patients in Korea.

Patients who experience clinical deterioration from coronavirus disease (COVID-19) require blood transfusion support. We analyzed blood component usage in COVID-19 patients and identified the predictors of red blood cell (RBC) transfusion in elderly (≥65 years) patients. Blood component usage in 882 COVID-19 patients hospitalized between January 24, 2020 and April 30, 2021 was analyzed. Elderly patients were categorized into transfused and non-transfused groups according to their RBC transfusion history; their demographic and clinical characteristics, disease severity, and outcomes were compared. Associations were determined using multiple logistic regression. The overall transfusion rate was 8.3% (73/882), and the transfusion rate was 2.7% (14/524) in patients aged <65 years and 16.5% (59/358) in those aged ≥65 years. Among the 358 elderly patients, 344 patients, including 50 who received transfusion and 294 who did not, were enrolled for the analysis. The prevalence of diabetes mellitus (DM), white blood cell count, absolute neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) on admission were significantly higher in the transfused group, whereas Hb and platelet counts were significantly lower. Disease severity in the transfused group was relatively high on admission and increased thereafter. DM, intensive care unit entrance on admission, Hb, platelet count, and NLR on admission were independently associated with RBC transfusion. This study presents transfusion rates in COVID-19 patients according to age groups and predictors of RBC transfusion in elderly patients. The results provide a basis for developing a strategy for the medical treatment of infectious diseases emerging during pandemics.

Estimating the effect of donor sex on red blood cell transfused patient mortality: A retrospective cohort study using a targeted learning and emulated trials-based approach.

SummaryBackgroundObservational studies determining the effect of red blood cell (RBC) donor sex on recipient mortality have been inconsistent. Emulating hypothetical randomized target trials using large real-world data and targeted learning may clarify potential adverse effects.MethodsIn this retrospective cohort study, a RBC transfusion database from the Capital Region of Denmark comprising more than 900,000 transfusion events defined the observational data. Eligible patients were minimum 18 years, had received a leukocyte-reduced RBC transfusion, and had no history of RBC transfusions within the past year at baseline. The doubly robust targeted maximum likelihood estimation method coupled with ensembled machine learning was used to emulate sex-stratified target trials determining the comparative effectiveness of exclusively transfusing RBC units from either male or female donors. The outcome was all-cause mortality within 28 days of the baseline-transfusion. Estimates were adjusted for the total number of transfusions received on each day k, hospital of transfusion, calendar period, patient age and sex, ABO/RhD blood group of the patient, Charlson comorbidity score, the total number of transfusions received prior to day k, and the number of RBC units received on each day k from donors younger than 40 years of age.FindingsAmong 98,167 adult patients who were transfused between Jan. 1, 2008, and Apr. 10, 2018, a total of 90,917 patients (54.6% female) were eligible. For male patients, the 28-day survival was 2.06 percentage points (pp) (95 % confidence interval [CI]: 1.81-2.32, P<0.0001) higher under treatment with RBC units exclusively from male donors compared with exclusively from female donors. In female patients, exclusively transfusing RBC units from either male or female donors increased the 28-day survival with 0.64pp (0.52-0.76, P<0.0001), and 0.62pp (0.49-0.75, P<0.0001) compared with the current practice, respectively. No evidence of a sex-specific donor effect was found for female patients (0.02pp [-0.18-0.22]). The sensitivity analyses showed that a large unknown causal bias would have to be present to affect the conclusions.InterpretationThe results suggest that a sex-matched transfusion policy may benefit patients. However, a causal interpretation of the findings relies on the assumption of no unmeasured confounding, treatment consistency, positivity, and minimal model misspecifications.FundingNovo Nordisk Foundation and the Innovation Fund Denmark.

Analysis of Baseline Clinical Characteristics and Disease Burden in Patients Enrolled in the International Paroxysmal Nocturnal Hemoglobinuria Registry

Background/Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening hematologic disorder characterized by chronic uncontrolled intravascular hemolysis, thrombosis, end organ damage, and impaired quality of life (QoL) and survival. The International PNH Registry (NCT01374360) is an ongoing, global observational study to evaluate the safety profile of eculizumab and to characterize the burden and progression of PNH including clinical outcomes, morbidity, and mortality irrespective of treatment. The objective of this analysis was to characterize the demographic and clinical characteristics, disease-associated morbidities, PNH symptoms, and health-related QoL of the largest cohort of PNH patients enrolled in the Registry.Methods: Registry patients who had data available as of May 1, 2017, were eligible for the current analysis. All patients were untreated at baseline, defined as the date of eculizumab initiation for patients ever treated with eculizumab and the date of Registry enrollment for patients never treated with eculizumab. Proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVE; including thrombotic events [TE]) and bone marrow disorders (BMD) including aplastic anemia, red blood cell (RBC) transfusions, concomitant medication use, and physician-reported symptoms were based on the number of patients with non-missing responses at baseline. Laboratory values and QoL scores assessed with the European Organisation for Research and Treatment of Cancer [EORTC] Global Health and Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue questionnaires within 6 months prior to baseline were summarized using medians and quartiles or proportions for the patients with non-missing responses. Patients with percent glycosylphosphatidylinositol (GPI)-deficient granulocyte values available prior to baseline were stratified based on the most recent value prior to baseline and statistical analysis (i.e., P values) was used to assess potential trends related to clone size.Results: A total of 4903 patients were enrolled. Of these, 4398 had non-missing data on demographics, enrollment date, and eculizumab status, and were eligible for the analysis. Median (Q1, Q3) age at disease onset was 35.3 (23.9, 53.1) years; 53% of the patients were female. Median (Q1, Q3) percent GPI-deficient granulocyte clone size was 33% (3%, 85%) in the 2654 patients with clone size reported prior to baseline. Clinical characteristics at baseline for the overall population and stratified by percent GPI-deficient clone size are summarized in the Table. Overall, patients had a high burden of disease at baseline, as reflected by the proportion with HDA (52%), history of MAVE (19%), BMD (63%), RBC transfusions (61%), and impaired renal function defined as estimated glomerular filtration rate <90 mL/min (42%). Patients frequently experienced symptoms such as fatigue (81%), dyspnea (45%), hemoglobinuria (45%), abdominal pain (35%), and impaired QoL with median (Q1, Q3) FACIT-Fatigue and EORTC Global Health scores of 34.0 (27.0, 40.0) and 58.3 (41.7, 75.0), respectively. All measures of disease burden except for history of RBC transfusions were significantly correlated with clone size (P <0.05); specifically, higher disease burden correlated with larger clone size. However, a substantial number of patients with clone size <10% had hemolysis (LDH ≥1.5 x ULN; 10%), MAVE (10%), HDA (9%), and/or experienced symptoms such as fatigue (82%), dyspnea (46%), abdominal pain (19%), or hemoglobinuria (13%). History of RBC transfusion and immunosuppressive therapy were reported in 60% and 59% of patients with clone size <10%, potentially due to patients with history of BMD. Interestingly, median LDH ratio and the proportion of patients with history of MAVE and TE were modestly higher in the cohort with clone size 10-<50% vs <10%, while the proportion of those patients was substantially higher in the cohort with clone size ≥50% vs 10-<50%.Conclusions: PNH is associated with high burden of disease, particularly in patients with larger GPI-deficient clone sizes; however, even patients with smaller clone sizes had significant disease burden and symptoms. Improved characterization of clinical measures and of relationships between these measures may help inform patient management. [Display omitted] DisclosuresSchrezenmeier:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Research Funding to University of Ulm . Maciejewski:Ra Pharma: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fees; Apellis Pharmaceuticals: Consultancy. Roeth:Roche: Consultancy, Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Araten:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Kanakura:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding; Astellas: Research Funding; Bristol Myers: Research Funding; Toyama Chemical: Research Funding; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Shionogi: Research Funding; Fujimotoseiyaku: Research Funding; Pfizer: Research Funding; Nippon Shinyaku: Research Funding; Chugai Pharmaceutical: Research Funding. Larratt:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Research Funding to the laboratory at University of Alberta, for ADAMTS13 testing. Shammo:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Shayan:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Celgene: Research Funding; Roche: Consultancy, Honoraria, Research Funding.

Maternal and perinatal outcomes in pregnant women with sickle cell disease: an update

IntroductionThe aim of this study was to describe maternal and perinatal outcomes in pregnant women with sickle cell disease (SCD) followed at Santa Casa de Sao Paulo over a 10-year period (between 2010 and 2019). MethodFifty-five records of pregnancies were analyzed among 35 women with SCD. ResultsAmong 29 newborns, 19 (65.5%) were full-term and 10 pre-term; 24 (82.7%) caesareans and 5 (17.2%) natural births were observed. The mean gestational age at birth and mother`s age were 36.6 weeks (30–40) and 26.7 years (17–39), respectively. No maternal death was observed. The main maternal obstetric and non-obstetric complications were: pre-eclampsia and gestational diabetes, and vaso-occlusive crisis, urinary tract infection and acute chest syndrome, respectively. Twenty-six (47.0%) fetal deaths were observed, 24 being intrauterine fetal (14 early abortions, 10 late abortions and 2 stillbirths). Regarding the red blood cell transfusion history, 40 (72.7%) out of 55 pregnancies received transfusion. Pregnant women who received 6 or more transfusions throughout pregnancy had a significantly lower number of abortions, i.e., no cases of early abortion and only 1 case of late abortion, versus 14 and 9 cases in pregnancies with 0–5 transfusions, respectively. Despite advances in the management of SCD, pregnant women with SCD (particularly those with HbSS) are at a high risk for maternal and fetal complications, even though they are followed in reference centers. ConclusionThe lower risk of intrauterine fetal death for those women who received more transfusions throughout pregnancy observed in the current study leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.

Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%–< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%–< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

Hepcidin and GDF15 Levels during the First 2 Years Follow-up in Patients with Low and Int-1 Risk Myelodysplastic Syndromes (MDS) from the European Leukemianet MDS Registry

Background: The EUMDS registry is a prospective observational registry to collect data on lower risk MDS. 17 Countries and 133 centers are participating. We analyzed serum from 101 patients for ferritin, hepcidin, growth differentiation factor 15 (GDF15) and C-reactive protein (CRP) at six-month intervals in order to evaluate temporal changes in iron metabolism.Objective: To explore hepcidin and GDF15 levels over time in lower risk MDS patients and their relation with WHO2001 subtype, transfusion history and conventional iron parameters.Results: The median age of the study population was 73 years (range 44-95 years). The majority was male: 64%. Distribution according to WHO2001 MDS subtype was RCMD (41%), RARS (25%), RA (14%), RAEB (11%), 5q-syndrome (6%) and RCMD-RS (3%). Table 1 shows iron parameters at registration, 1 year and 2 years follow-up both in transfusion-dependent (TD) and transfusion-independent (TI) patients and stratified according to MDS subtypes: RS (RARS/RCMD-RS) or MDS Other (RA/RCMD/RAEB/5q-syndrome). Serum ferritin was increased in TD patients with a median concentration at registration of 550µg/L and at 2 years 818µg/L, compared to TI patients (median <250µg/L, all time points). During follow-up ferritin was most elevated in patients who received >10 red blood cell (RBC) units: median at registration 1482µg/L - 2 years 1970µg/L. Ferritin correlated significantly with hepcidin (r=0.57; p<0.001) as well as CRP: r=0.27, p<0.001. Median CRP was within reference range (<10mg/L) for both TD and TI patients at registration and during follow-up, but mainly TD patients had elevated CRP levels >50mg/L. Median serum hepcidin levels were elevated in TD patients at registration and remained elevated during follow-up, especially in patients with >10 RBC units transfused (median 27.4nmol/l at registration, 12.8nmol/l at 2 years). Remarkable fluctuation in hepcidin levels occurred in patients with elevated hepcidin during follow-up. Even in the longitudinal cohorts hepcidin fluctuated considerably, maybe due to the interval between the previous transfusion and the measurement of hepcidin or due to diurnal fluctuation. Hepcidin was lowest in MDS RS TI patients and showed a tendency to decrease over time from a median level of 4.4nmol/l at registration to 2.4nmol/l after 2 years, associated with ineffective erythropoiesis. This is supported by the high median GDF15 in these patients. Lowest GDF15 was found in TD patients with ‘MDS Other’ associated with transfusional load. The number of transfused RBC units did not affect the median GDF15 levels.Conclusions: Hepcidin levels were influenced by RBC transfusion history, but hepcidin levels appear to decrease over time in the RS subtype only. Interestingly, increase in hepcidin after transfusions was already visible early in follow-up, depending on the transfusional load and erythropoietic activity of the bone marrow. GDF15 concentration appeared to be most related to MDS subtype, functioning as a marker of ineffective erythropoiesis.Table1:ferritin, hepcidin and GDF15 during-follow-upRegistration1 yr follow-up2 yrs follow-upNMedian(p25-p75)NMedian(p25-p75)NMedian(p25-p75)Ferritin (µg/L)101286 (138 - 558)83287 (149 - 845)66347 (191 - 818)MDS Other: TI53205 (87 - 389)31148 (78 - 288)25202 (71 - 319)MDS Other: TD20479 (279 - 877)29845 (481 - 1538)22841 (323 - 2387)RARS/RCMD-RS: TI25268 (195 - 558)19233 (170 - 323)10319 (222 - 379)RARS/RCMD-RS: TD3610 (108 - 1382)41909 (1206 - 2935)9712 (590 - 1222)Hepcidin (nmol/L)1005.2 (3.0 - 9.9)835.8 (2.7 - 14.0)665.2 (2.5 - 9.9)MDS Other: TI534.6 (2.8 - 8.4)314.4 (2.3 - 8.1)254.2 (2.5 - 6.8)MDS Other: TD2011.1 (4.9 - 21.0)2917.2 (9.2 - 22.3)229.6 (4.5 - 17.1)RARS/RCMD-RS: TI244.2 (2.1 - 6.1)193.5 (1.6 - 5.1)102.4 (1.6 - 3.9)RARS/RCMD-RS: TD39.8 (6.0 - 11.1)49.3 (7.3 - 12.1)95.2 (2.9 - 9.3)TI: 0 RBC units814.5 (2.8 - 8.4)514.0 (2.0 - 7.5)373.1 (2.1 - 6.7)TD: ≤10 RBC units1710.6 (4.7 - 14.9)149.2 (5.3 - 17.2)144.3 (2.4 - 8.7)TD: >10 RBC units227.4 (15.7 - 39.1)1818.1 (12.7 - 24.5)1512.8 (9.3 - 21.3)GDF15 (ng/L)1011945 (1207 - 3611)822467 (1659 - 4318)662582 (1519- 5332)MDS Other: TI531831 (1100 - 3176)311902 (1076 - 2698)251702 (1136 - 3564)MDS Other: TD201452 (1169 - 2789)282583 (1937 - 4493)222556 (1661 - 4050)RARS/RCMD-RS: TI253532 (2124 - 4211)193148 (2195 - 4560)103661 (1986 - 5524)RARS/RCMD-RS: TD32196 (1869 - 2893)42996 (1806 - 5141)95555 (3204 - 7488) DisclosuresHellström-Lindberg:Celgene: Research Funding. Symeonidis:Celgene: Research Funding; Novartis Oncology: Research Funding; Amgen: Research Funding; Novartis Oncology: Consultancy; Amgen: Consultancy. de Witte:Novartis: Research Funding; Novartis: Honoraria; Celgene: Consultancy; Novartis: Consultancy.

Development and validation of a model to predict platelet response to romiplostim in patients with lower-risk myelodysplastic syndromes.

Low endogenous erythropoietin levels and limited red blood cell transfusion history can predict response to erythropoiesis-stimulating agents in anaemic patients with myelodysplastic syndromes (MDS). The relationship between endogenous thrombopoietin (THPO) levels and platelet response to romiplostim is unknown. Variables including baseline endogenous THPO levels, transfusion needs, and platelet response were analysed in a randomized trial of 250 thrombocytopenic, lower-risk MDS patients (International Prognostic Scoring System low/intermediate-1). A predictive scoring system was developed based on log-likelihood ratios and logistic coefficients. Patients with HI-P (haematological improvement - platelets) responses had lower mean baseline THPO levels (P = 0·0497) and were more likely to have <6 platelet units transfused in the past year (P = 0·0027), as did patients with platelet responses ≥50% of weeks on romiplostim (P = 0·001 and P = 0·0037, respectively). A model for predicting response to romiplostim was developed and validated in a separate MDS cohort (N = 72). Patients in low-, intermediate-, and high-response groups had response rates of 17·4%, 29·6%, and 50·7%, respectively, for HI-P, and 17·4%, 33·8%, and 65·2%, respectively, for ≥50% response. For thrombocytopenic patients with lower-risk MDS, lower baseline THPO levels (<500 pg/ml) and limited platelet transfusion history predicted a greater likelihood of a subsequent platelet response to romiplostim.

Do Red Cell Transfusions Increase the Risk of Necrotizing Enterocolitis in Premature Infants?

To test the hypothesis that red blood cell (RBC) transfusions increase the risk of necrotizing enterocolitis (NEC) in premature infants, we investigated whether the risk of "transfusion-associated" NEC is higher in infants with lower hematocrits and advanced postnatal age. Retrospective comparison of NEC patients and control patients born at < 34 weeks gestation. The frequency of RBC transfusions was similar in NEC patients (47/93, 51%) and control patients (52/91, 58%). Late-onset NEC (> 4 weeks of age) was more frequently associated with a history of transfusion(s) than early-onset NEC (adjusted OR, 6.7; 95% CI, 1.5 to 31.2; P = .02). Compared with nontransfused patients, RBC-transfused patients were born at earlier gestational ages, had greater intensive care needs (including at the time of onset of NEC), and longer hospital stay. A history of RBC transfusions within 48-hours before NEC onset was noted in 38% of patients, most of whom were extremely low birth weight infants. In most patients, RBC transfusions were temporally unrelated to NEC and may be merely a marker of overall severity of illness. However, the relationship between RBC transfusions and NEC requires further evaluation in extremely low birth weight infants using a prospective cohort design.

Risk Factors for the Presence of non-Rhesus D Red Blood Cell Antibodies in Pregnancy

Koelewijn, J.M.; Vrijkotte, T.G.; de Haas, M.; van der Schoot, C.E.; Bonsel, G.J. Author Information

Association of iron overload (IO) with time to progression (TTP) in patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplant (HSCT).

e17003 Background: IO resulting principally from red blood cell (RBC) transfusions is not an uncommon complication in HSCT recipients. Organ dysfunction and increased risk of infection associated with IO in early post-transplant period is increasingly being reported. Long-term effects of IO including risk of relapse/progression are less well described. Methods: A retrospective chart review identified 26 patients diagnosed with MM and treated with high-dose melphalan (200 mg/m2) followed by autologous HSCT at our institution from 1999 to 2007. Patients with serum ferritin level (F) 1,000 ng/dl, measured at steady state (3–24 mos post transplant), were compared regarding demographics, disease stage, disease type, end organ complications, β-2 microglobulin, presence of adverse chromosomal abnormalities, RBC transfusion history and TTP as measured by the international myeloma working group criteria. Results: Results are shown in the Table. Five patients had F>1000 ng/dL and 21 <1,000 ng/dL with median...

Risk factors for the presence of non‐rhesus D red blood cell antibodies in pregnancy*

To identify risk factors for the presence of non-rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years. Case-control study. Nationwide evaluation of screening programme for non-RhD RBC antibodies. consecutive pregnancies (n=900) with non-RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n=968): matched for obstetric caregiver and gestational age. Data collection from the medical records and/or from the respondents by a structured phone interview. Significant risk factors for non-RhD immunisation in multivariate analysis. Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4-24.6), parity (para-1 versus para-0: OR 1.3; 95% CI: 1.0-1.7; para-2 versus para-0: OR 1.4; 95% CI: 1.0-2.0; para >2 versus para-0: OR 3.2; 95% CI: 1.8-5.8), haematological disease (OR 2.1; 95% CI: 1.0-4.2), history of major surgery (OR 1.4; 95% CI: 1.1-1.8). For the clinically most important antibodies, anti-K, anti-c and other Rh-nonD-antibodies RBC transfusion was the most important risk factor, especially for anti-K (OR 96.4; 95%-CI: 56.6-164.1); 83% of the K-sensitised women had a history of RBC transfusion. Pregnancy-related risk factors were a prior male child (OR 1.7; 95% CI: 1.2-2.3) and caesarean section (OR 1.7; 95% CI: 1.1-2.7). RBC transfusion is by far the most important independent risk factor for non-RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy-related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD-positive para-0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.

Incidence of HFE Gene Mutations in Chinese Patients with Myelodysplastic Syndrome and Aplastic Anemia

The C282Y and H63D mutations of HFE gene responsible for hereditary hemochromatosis lead to absorption of excess dietary iron, tissue iron deposition and occurrence of clinical complications such as congestive heart failure, arrhythmia, hepatocellular cirrhosis, insulin resistance and diabetes. Iron overload is one important clinical feature in patients with myelodysplastic syndrome (MDS) and aplastic anemia(AA). However, the conflict has been existing about influence of HFE gene mutations on iron overload in MDS patients. In the present study, we analyzed the incidence of the C282Y and H63D mutations of HFE gene in 271 MDS patients, 402 AA patients and 1615 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No C282Y mutations and compound heterozygote were observed in the entire cohort. The genotype distribution of H63D heterozygous and homozygous did not differ significantly in AA cases from those in controls(9.7%vs. 10.2%, 0.25%vs. 0.24% respectively, Pearson Chi-square p both >0.05). While the frequency of the H63D heterozygous in MDS patients was significantly lower than controls (4.1%vs. 10.7%, Pearson Chi-square p=0.002). H63D homozygous was not found in MDS patients. The incidence of C282Y and H63D mutations of HFE gene in Chinese MDS cases is lower than those reported in the literature. Comparing the pretransfusion serum ferritin(SF), serum iron concentration(SI) and transferrin saturation values(TS) between HFE-mutation and HFE-wild MDS groups, we did not find a significant difference (all P>0.05); However, Only SI values were significantly higher in the HFE-mutation AA cases than those in HFE-wild ones[42.6(24.6–60.4)umol/Lvs. 32.0(8.4–63.3)umol/L, P=0.011]. We further estimated the function of important organs in MDS and AA patients. There is no significantly difference in Alanine amino transferase (ALT), Aspartate amino transferase (AST), fasting blood sugar, and electrocardiogram(ECG) between HFE-mutation and HFE-wild MDS and AA groups irrespective of the red blood cell transfusion history. The results suggest that the distribution of C282Y and H63D mutations has ethnic and genetic differences, and is very rare in Chinese population. The mutations of HFE gene are not main factors of iron overload in Chinese patients with myelodysplastic syndrome and aplastic anemia.