Anemia, also referred to as low hemoglobin level, is a common finding in critically ill patients. Red blood cell (RBC) transfusion is used to increase patients’ hemoglobin level. Approximately 26 -... Show moreAnemia, also referred to as low hemoglobin level, is a common finding in critically ill patients. Red blood cell (RBC) transfusion is used to increase patients’ hemoglobin level. Approximately 26 - 40% of critically ill patients receive RBC transfusions during their stay in the Intensive Care Unit (ICU), making transfusion a substantial element of critical care practice. Current available evidence supports utilising a restrictive transfusion trigger of 7 g/dL in non-bleeding ICU patients. A burning question is whether 7 g/dL is the optimal trigger for all non-bleeding ICU patients. This research focused on increasing our understanding of clinicians’ red cell transfusion decisions, of possible consequences of red cell transfusion in individual non-bleeding critically ill patients, and on the methodology to achieve the latter goal.We showed that there is considerable variation in transfusion decisions amongst critical care physicians, suggesting that clinicians have varying ideas about benefits of transfusion. We identified clinical determinants of transfusion decisions, because these determinants might be associated with observed effects of RBC transfusion. The data were derived from the electronic medical health records of ICU patients. Our results confirmed that besides hemoglobin concentration, inherently the most important predictor of RBC transfusion, a number of other clinical parameters were associated with transfusion decisions. Using the same data, we developed a model for the prediction of the effect of RBC transfusion on subsequent organ functioning in non-bleeding critically ill patients. Show less
Winter, D.P. de; Hulzebos, C.; Oever, R.M. van 't; Haas, M. de; Verweij, E.J.T.; Lopriore, E. 2022
Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and... Show moreSince the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle- to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps. Conclusion: Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. What is Known: Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre- and postnatal treatment. What is New: This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Future studies should be set in an international setting with the ultimate aim of eradicating HDFN. Show less
Oever, R.M. van 't; Zwiers, C.; Winter, D. de; Haas, M. de; Oepkes, D.; Lopriore, E.; Verweij, E.J. 2022
Introduction Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in... Show moreIntroduction Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. Areas covered This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. Expert opinion In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause. Show less
Twin anemia polycythemia sequence (TAPS) is a chronic form of unbalanced feto-fetal transfusion through minuscule placental anastomoses in monochorionic twin pregnancies, leading to anemia in the... Show moreTwin anemia polycythemia sequence (TAPS) is a chronic form of unbalanced feto-fetal transfusion through minuscule placental anastomoses in monochorionic twin pregnancies, leading to anemia in the donor twin and polycythemia in the recipient twin. TAPS can occur spontaneously in up to 5% of monochorionic twins or can arise in 2%-16% of cases after incomplete laser surgery for twin-twin transfusion syndrome. TAPS can develop across the entire second and third trimester. Antenatal diagnosis for TAPS is reached via Doppler measurement of the fetal middle cerebral artery peak systolic velocity, showing an increased velocity in the donor, combined with a decreased velocity in the recipient. Treatment options for TAPS include expectant management, preterm delivery, intrauterine blood transfusion with or without a partial exchange transfusion, fetoscopic laser surgery and selective feticide. The best treatment option is unclear and is currently being investigated in an international multicenter randomized trial (the TAPS trial). Spontaneous fetal demise occurs in 5%-11% of TAPS twins, more often in donors (8%-18%) than in recipients (2%-5%). Severe long-term neurodevelopmental impairment is seen in 9% of TAPS twins, with donors having an increased risk for cognitive impairment and hearing problems (15%). Show less
Background Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on... Show moreBackground Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction. Methods The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination. Results Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04-1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65-2.11). Conclusion In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial. Show less
Fustolo-Gunnink, S.F.; Roehr, C.C.; Lieberman, L.; Christensen, R.D.; Bom, J.G. van der; Dame, C.; ... ; Lopriore, E. 2019
Knowledge of physiological changes in renal function, EPO and haemoglobin level and their impact at old age are essential for clinicians especially those working with older patients. The results of... Show moreKnowledge of physiological changes in renal function, EPO and haemoglobin level and their impact at old age are essential for clinicians especially those working with older patients. The results of the studies presented in this thesis provide more insight in the physiological aspects of age related decline in renal function and the relation with erythropoietin production and the maintenance of haemoglobin levels at old age. Furthermore, these results allow us to speculate about the predictive value of renal function, EPO and haemoglobin as markers of mortality in a clinical population of oldest old patients. Proper knowledge of these markers could contribute to increased attention of clinicians for the increased mortality risk of their oldest old patients. Furthermore, knowledge of these markers could be helpful in tailor made medicine, individual prognostication and decision making procedures, in the oldest old patients. Show less
In this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term... Show moreIn this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term and long-term outcome of children with Rhesus hemolytic disease. Show less
Red blood cells (RBCs) are probably the most frequently used drug given to very preterm infants; more than 90% of infants with a birth weight <1000 grams receive one or more RBC transfusions.... Show moreRed blood cells (RBCs) are probably the most frequently used drug given to very preterm infants; more than 90% of infants with a birth weight <1000 grams receive one or more RBC transfusions. Except for reduction of the amount of blood drawn for laboratory tests and use of a single donor program, no measures have been shown to be an irrefutable safe way to reduce donor exposure. Preventative measures for anemia should be used to reduce the number of RBC transfusions needed. Alternatives for allogenic RBC transfusions, such as autologous RBC cord blood transfusion, should be further explored and implemented. A restrictive transfusion strategy does not seem harmful for the children in short term or long term outcome. Thrombocytopenia is also a frequently encountered problem in neonatal medicine with an increased risk for hemorrhage. Thrombocytopenia, irrespective of the severity, increases the incidence of intraventricular hemorrhage. A more restrictive platelet transfusion policy significantly reduces the number of infants receiving a platelet transfusion without a difference in occurrence of (severe) hemorrhage. We state that both for red blood cell and platelet transfusions in (premature) newborn infants, safe thresholds are still not established. Transfusions may have (late) detrimental effects. Safe thresholds for both erythrocytes and platelets need to be found by large prospective randomized trials focusing not only on the direct effects but also on the long-term effects. Show less
The aim of this thesis was to study the impact and etiology of anemia in the oldest old in the general population, in order to support the development of evidence-based diagnostic and treatment... Show moreThe aim of this thesis was to study the impact and etiology of anemia in the oldest old in the general population, in order to support the development of evidence-based diagnostic and treatment recommendations for anemia in the oldest old. All studies presented in this thesis were embedded in the Leiden 85-plus Study and the Newcastle 85-plus Study. First, the impact of anemia was investigated. Anemia in old age appeared to be associated with an increased risk of death, independent of comorbidity, but the associated functional decline appeared to be attributed mainly to comorbidity. In various chapters, the etiology of anemia in old age was studied. An important finding was that, while folate deficiency at age 85 years was associated with the development of anemia during follow-up, vitamin B12 deficiency was not. In addition, low ferritin was associated with lower hemoglobin levels, but this association was more pronounced in participants with inflammation than in participants without inflammation. In the general discussion, a description of the possible clinical implications of this thesis and recommendations for further studies are provided. Show less
In this thesis fetal fluid and protein dynamics are investigated to gain insight in fetal (patho-)physiology. Studies were performed in fetuses with severe anemia and/or hydrops fetalis.... Show moreIn this thesis fetal fluid and protein dynamics are investigated to gain insight in fetal (patho-)physiology. Studies were performed in fetuses with severe anemia and/or hydrops fetalis. Measurements were performed in fetal blood or amniotic fluid, obtained before or during intrauterine transfusion. The severity of anemia can be predicted by measurement of bilirubin in amniotic fluid. We showed that this concentration is based on bilirubin in fetal blood and on albumin concentrations. Albumin in amniotic fluid is most probably not of fetal however of membrane or maternal origin. Thus, bilirubin seems to exchange between albumin in fetal blood and amniotic fluid over the intramembraneous pathway. Low albumin concentration in fetal blood seems to be a secondary effect of hydrops fetalis. Fetuses with severe anemia were found to maintain their total blood volume. Thus, the decrease in red cell volume is compensated by an increase in plasma volume. This could explain the decrease in albumin concentration. During intrauterine transfusion, part of the plasma volume leaves the circulation. It is expected that this process continues after transfusion, thus further increasing the hematocrit. Acquired insights and differences between fetuses and neonates are discussed. Finally, implications for current practice and future research are described. Show less
