Umbilical Cord Blood as an Alternative to Neonatal Blood for Complete Blood Count: A Comparison Study.

OBJECTIVE: To assess concordance between umbilical cord blood (UCB) and neonatal blood (NB) laboratory test results at birth. STUDY DESIGN: This retrospective study considered very preterm neonates (<32 weeks' gestational age) admitted to a tertiary neonatal intensive care unit from 2012 to 2023. Inclusion criteria required neonates with a complete blood count measured in both UCB and NB drawn within 2 hours after birth. Median hemoglobin (Hb) and hematocrit (Hct) concentrations were compared between UCB (venous samples) and NB (venous, arterial, or capillary samples). RESULTS: A total of 432 neonates with paired UCB and NB values were included in the study. Hb concentration in UCB was 14.7 g/dL (IQR 13.5-16.1 g/dL) compared with 14.8 g/dL (IQR 12.6-19.3 g/dL) in venous NB samples, 13.9 g/dL (IQR 12.9-15.3 g/dL) in arterial NB and 18.7 g/dL (IQR 16.6-20.8 g/dL) in capillary NB. The regression equation showed a correction factor of 1.08 for converting Hb values from UCB to venous NB. Median Hct concentration in UCB was 0.45 L/L (IQR: 0.41-0.49 L/L) compared with 0.48 L/L (IQR 0.43-0.54 L/L) in venous NB, 0.42 L/L (IQR 0.38-0.45 L/L) in arterial NB and 0.57 L/L, (IQR 0.51-0.63 L/L) in capillary NB. CONCLUSIONS: Hb and Hct concentrations measured in UCB are similar to those measured in venous blood in very preterm infants and are valid alternatives for NB tests at birth. Hb and Hct concentrations in arterial and capillary NB are respectively lower and higher compared with UCB measurements.

Transfusion of ever-pregnant donor red blood cells and mortality of male patients.

Previous studies found exposure to red blood cell transfusions from female donors who have been pregnant reduces survival in male patients compared to exposure to male donor products, but evidence is not consistent. We postulate the previously observed association is modified by offspring sex, with an expected increased mortality risk for male patients receiving units from female donors with sons. Here, marginal structural models were used to assess the association between exposure to units from ever-pregnant donors, ever-pregnant donors with sons and ever-pregnant donors with daughters, and mortality. Clinical data were collected on first-ever transfusion recipients in the Netherlands and donor data were supplemented with information about offspring sex and date of birth. In this analysis, 56,825 patients were included, of whom 8,288 died during follow-up. Exposure to red blood cell units from ever-pregnant donors with sons was not associated with increased all-cause mortality risk among male transfusion recipients (hazard ratio [HR]=0.91, 95% confidence interval [CI]: 0.83-1.01). Exposure to ever-pregnant donors, irrespective of offspring sex, was associated with mortality in male patients aged between 18 and 50 years (ever-pregnant donors: HR=1.81, 95% CI: 1.31-2.51) compared to male donor units, but was protective in female patients. This study suggests that the observed increased mortality risk for exposure to red blood cell units from parous female donors does not depend on offspring sex. The increased risk of mortality seen in younger adult male patients is consistent with previous observations, but the underlying biological mechanism could not be identified in this study.

Donor pregnancies and transfusion recipient mortality: A role for red blood cell storage?

BACKGROUND AND OBJECTIVES: Donor characteristics have been implicated in transfusion-related adverse events. Uncertainty remains about whether sex, and specifically pregnancy history of the blood donor, could affect patient outcomes. Whether storage duration of the blood product could be important for patient outcomes has also been investigated, and a small detrimental effect of fresh products remains a possibility. Here, we hypothesize that fresh red blood cell products donated by ever-pregnant donors are associated with mortality in male patients. MATERIALS AND METHODS: We used data from a cohort study of adult patients receiving a first transfusion between 2005 and 2015 in the Netherlands. The risk of death after receiving a transfusion from one of five exposure categories (female never-pregnant stored ≤10 days, female never-pregnant stored >10 days, female ever-pregnant stored ≤10 days, female ever-pregnant stored >10 days and male stored for ≤10 days), compared to receiving a unit donated by a male donor, which was stored for >10 days (reference), was calculated using a Cox proportional hazards model. RESULTS: The study included 42,456 patients who contributed 88,538 person-years in total, of whom 13,948 died during the follow-up of the study (33%). Fresh units (stored for ≤10 days) from ever-pregnant donors were associated with mortality in male patients, but the association was not statistically significant (hazard ratio 1.39, 95% confidence interval 0.97-1.99). Sensitivity analyses did not corroborate this finding. CONCLUSION: These findings do not consistently support the notion that the observed association between ever-pregnant donor units and mortality is mediated by blood product storage.

Predicting organ functioning with and without blood transfusion in critically ill patients with anemia.

BACKGROUND: To develop a model for the prediction of the (most likely) effect of red blood cell (RBC) transfusion on subsequent organ functioning in nonbleeding critically ill patients with hemoglobin concentrations between 6 and 9 g/dL. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using electronic health care data of nonbleeding patients admitted between November 2004 and May 2016 at the intensive care unit (ICU) of the Leiden University Medical Center, The Netherlands. We analyzed the associations between transfusion (yes/no) and next-day SOFA scores (Sequential Organ Failure Assessment-as a measure for organ functioning) for all observed combinations of hemoglobin values (between 6 and 9 g/dL) and concurrent clinical variables. RESULTS: Data of 6425 ICU admission of 5756 critically ill patients with 28,702 hemoglobin values between 6 and 9 g/dL (transfusion decision moments) of which 22.1% were followed by a transfusion were analyzed. The adjusted average difference between the next-day SOFA score of transfused versus not-transfused patients was 0.08 (95% confidence interval [CI] -0.03 to 0.18). At singular transfusion decision moments, the score predicted a beneficial effect of transfusion on next-day SOFA score for some subgroups and medical conditions and a harmful effect in other occasions. CONCLUSIONS: Among these critically ill patients with hemoglobin concentrations between 6 and 9 g/dL the population average effect of transfusion on the next SOFA score was negligible. Further, our results support caution in clinical decision-making regarding transfusion of critical ill, nonbleeding ICU patients.

Association between cardiovascular risk factors and intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia-related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. OBJECTIVES: Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. METHODS: In a case-control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55 matched control patients without intracranial hemorrhage, data on cardiovascular risk factors were collected for all patients. Analyses were performed via conditional logistic regression. RESULTS: Pre-existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval [CI] 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. CONCLUSION: Both pre-existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients.

Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM® ) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage. MATERIAL AND METHODS: During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve (AUC) and positive and negative predictive values. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149472). RESULTS: Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively. CONCLUSIONS: Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.

Expected individual benefit of prophylactic platelet transfusions in hemato-oncology patients based on bleeding risks.

BACKGROUND: Prophylactic platelet transfusions prevent bleeding in hemato-oncology patients, but it is unclear how any benefit varies between patients. Our aim was to assess if patients with different baseline risks for bleeding benefit differently from a prophylactic platelet transfusion strategy. STUDY DESIGN AND METHODS: Using the data from the randomized controlled TOPPS trial (Trial of Platelet Prophylaxis), we developed a prediction model for World Health Organization grades 2, 3, and 4 bleeding risk (defined as at least one bleeding episode in a 30 days period) and grouped patients in four risk-quartiles based on this predicted baseline risk. Predictors in the model were baseline platelet count, age, diagnosis, disease modifying treatment, disease status, previous stem cell transplantation, and the randomization arm. RESULTS: The model had a c-statistic of 0.58 (95% confidence interval [CI] 0.54-0.64). There was little variation in predicted risks (quartiles 46%, 47%, and 51%), but prophylactic platelet transfusions gave a risk reduction in all risk quartiles. The absolute risk difference (ARD) was 3.4% (CI -12.2 to 18.9) in the lowest risk quartile (quartile 1), 7.4% (95% CI -8.4 to 23.3) in quartile 2, 6.8% (95% CI -9.1 to 22.9) in quartile 3, and 12.8% (CI -3.1 to 28.7) in the highest risk quartile (quartile 4). CONCLUSION: In our study, generally accepted bleeding risk predictors had limited predictive power (expressed by the low c-statistic), and, given the wide confidence intervals of predicted ARD, could not aid in identifying subgroups of patients who might benefit more (or less) from prophylactic platelet transfusion.

Thrombocytopenia and the effect of platelet transfusions on the occurrence of intracranial hemorrhage in patients with acute leukemia - a nested case-control study.

We designed a study to describe the incidence of intracranial hemorrhage according to severity and duration of thrombocytopenia and to quantify the associations of platelet transfusions with intracranial hemorrhage in patients with acute leukemia. In this case-control study nested in a cohort of 859 leukemia patients, cases (n = 17) were patients diagnosed with intracranial hemorrhage who were matched with control patients (n = 55). We documented platelet counts and transfusions for seven days before the intracranial hemorrhage in cases and in a "matched" week for control patients. Three measures of platelet count exposure were assessed in four potentially important time periods before hemorrhage. Among these leukemia patients, we observed the cumulative incidence of intracranial hemorrhage of 3.5%. Low platelet counts were, especially in the three to seven days preceding intracranial hemorrhage, associated with the incidence of intracranial hemorrhage, although with wide confidence intervals. Platelet transfusions during the week preceding the hemorrhage were associated with higher incidences of intracranial hemorrhage; rate ratios (95% confidence interval) for one or two platelet transfusions and for more than two transfusions compared with none were 4.04 (0.73 to 22.27) and 8.91 (1.53 to 51.73) respectively. Thus, among acute leukemia patients, the risk of intracranial hemorrhage was higher among patients with low platelet counts and after receiving more platelet transfusions. Especially, the latter is likely due to clinical factors leading to increased transfusion needs.

Platelet transfusion and tranexamic acid to prevent bleeding in outpatients with a hematological disease: A Dutch nationwide survey.

OBJECTIVES: There is scarce evidence about the effectiveness of anti-bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical practice and clinicians' considerations on the administration of prophylactic platelet transfusions and tranexamic acid (TXA) to outpatients with acute leukemia, myelodysplastic syndrome (MDS), or aplastic anemia (AA) in the Netherlands. METHODS: We conducted an online survey among members of the Dutch Society for Hematology. RESULTS: The survey was filled out by 73 respondents. Prophylactic platelet transfusions are widely used in acute leukemia and MDS outpatients receiving disease-modifying treatments (87%-98% of respondents). TXA is predominantly prescribed in case of bleeding (tendency) (71%-88% of respondents). Conditions potentially increasing bleeding risks highly variably influence clinicians' decision making on anti-bleeding regimens, which includes a wide range in adhered platelet thresholds. CONCLUSION: Considering that both the contribution of prophylactic platelet transfusions as well as TXA to limiting bleeding is insufficiently evidence-based, there is an urgent need for trials on optimal anti-bleeding strategies in this outpatient population, which should encompass efficacy, logistic, financial, and quality-of-life aspects.

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: To evaluate rotational fibrin-based thromboelastometry (ROTEM® FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen. MATERIAL AND METHODS: Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500  ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of ≥4 packed cells, and/or (3) need for an invasive intervention to cease bleeding. RESULTS: Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 ≤12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen ≤2 g/L. CONCLUSIONS: The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.

Transition from fresh frozen plasma to solvent/detergent plasma in the Netherlands: comparing clinical use and transfusion reaction risks.

Plasma transfusion is indicated for replenishment of coagulative proteins to stop or prevent bleeding. In 2014, the Netherlands switched from using ~300mL fresh frozen plasma (FFP) units to using 200mL Omniplasma, a solvent/detergent treated pooled plasma (SD plasma), units. We evaluated the effect of the introduction of SD plasma on clinical plasma use, associated bleeding, and transfusion reaction incidences. Using diagnostic data from six Dutch hospitals, national blood bank data, and national hemovigilance data for 2011 to 2017, we compared the plasma/red blood cell (RBC) units ratio (f) and the mean number of plasma and RBC units transfused for FFP (~300mL) and SD plasma (200mL) for various patient groups, and calculated odds ratios comparing their associated transfusion reaction risks. Analyzing 13,910 transfusion episodes, the difference (Δf = fSD - fFFP) in mean plasma/RBC ratio (f) was negligible (Δfentire_cohort = 0.01 [95% confidence interval (CI): -0.02 - 0.05]; P=0.48). SD plasma was associated with fewer RBC units transfused per episode in gynecological (difference of mean number of units -1.66 [95% CI: -2.72, -0.61]) and aneurysm (-0.97 [-1.59, -0.35]) patients. SD plasma was further associated with fewer anaphylactic reactions than FFP (odds ratio 0.37 [0.18, 0.77; P<0.01]) while the differences for most transfusion reactions were not statistically significant. SD plasma units, despite being one third smaller in volume than FFP units, are not associated with a higher plasma/RBC ratio. SD plasma is associated with fewer anaphylactic reactions than FFP plasma/RBC units ratio.

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age <34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count <50x109/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions. The study was registered at www.clinicaltrials.gov (NCT03110887).

Mortality of patients with haemophilia in Brazil: First report.

INTRODUCTION: Brazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown. AIM: To analyse mortality and its causes in Brazilian patients with haemophilia from 2000 to 2014. METHODS: The number of deceased patients with haemophilia and causes of death were obtained from the Brazilian National Mortality Information System (SIM), according to the 10th International Classification of Diseases (ICD-10). Standardized mortality ratios (SMR) were calculated to estimate the rate of overall death of patients with haemophilia relative to that of the Brazilian general male population. RESULTS: A total of 784 deaths were identified in the period of 15 years. Mortality of patients with haemophilia was 13% higher when compared with the general male population (SMR 1.13, 95% CI: 1.01-1.16). Haemorrhage was the main cause of death (n = 254; 32.4%) of which 137 (54%) was intracranial haemorrhage. The total number of deaths due to HIV decreased over the years, and an increase in deaths due to cancer and cardiovascular disease was observed. A total of 129 deaths (16.5%) were related to hepatitis infection, of whom, 109 (86.5%) patients also presented with cirrhosis and hepatocellular carcinoma or other liver diseases. CONCLUSION: Mortality rate of Brazilian patients with haemophilia decreased over the evaluated period. Intracranial haemorrhage is still an important cause of death in these patients, which requires major effort for prevention. Death due to age-related cardiovascular disease and cancer has increased over the years, following the same tendency observed in developed countries.

Determinants of transfusion decisions in the ICU: haemoglobin concentration, what else? - a retrospective cohort study.

BACKGROUND AND OBJECTIVES: The aim of this study was to assess potentially relevant clinical characteristics which influence the decision to transfuse red cells in critically ill patients with low haemoglobin concentrations (6.0-10.0 g/dl). MATERIALS AND METHODS: This was a retrospective observational cohort study of patients admitted between November 2004 and May 2016 at the intensive care unit (ICU) of the Leiden University Medical Center, Netherlands. Haemoglobin measurements, clinical variables and the subsequent transfusion decision were extracted from the electronic health records. Clinical variables were grouped by organ system. We first examined the association of each of the clinical variables with the decision to transfuse during the following 6 h after a haemoglobin measurement using generalized estimating equations. We then compared the predictive abilities of single variables within an organ system and the predictive ability of an organ system's combined variables using the change in Akaike information criterion (AIC). RESULTS: A total of 83 394 haemoglobin measurements of 10 947 ICU admissions were included. Haemoglobin concentration was the most predictive for red cell transfusion. After the haemoglobin concentration, the combined variables for General Health, followed by the organ systems Cardiovascular and Pulmonary, were most predictive for red cell transfusion. Within these organ systems, the APACHE II score, referring department, APACHE admission diagnosis subgroup, troponin concentration, lactate concentration, respiratory rate, PaO2 /FiO2 and ventilation mode had the highest predictive ability. CONCLUSION: Haemoglobin concentration is the dominant predictor for red cell transfusion. Other clinical characteristics are also predictive, though to a lesser extent.

Comparison of outcome between intrauterine balloon tamponade and uterine artery embolization in the management of persistent postpartum hemorrhage: A propensity score-matched cohort study.

INTRODUCTION: The aim of this study was to compare the outcomes of women who were initially managed by intrauterine balloon tamponade or uterine artery embolization because of persistent postpartum hemorrhage demanding an immediate intervention to control bleeding. MATERIAL AND METHODS: Propensity score-matched cohort study including women who had intrauterine balloon tamponade or uterine artery embolization as initial management strategy to control persistent postpartum hemorrhage, that is, refractory to first-line therapy combined with at least one uterotonic agent. The primary outcome measure was a composite of peripartum hysterectomy and/or maternal mortality. Secondary outcomes measures were total volume of blood loss and total number of packed red blood cells transfused. RESULTS: Our 1:1 propensity score-matched cohort comprised of 50 women who had intrauterine balloon tamponade and 50 women who underwent uterine artery embolization at a blood loss between 1000 and 7000 mL. There was no statistically significant difference in the hysterectomy risk between the two groups (n = 6 in each group, odds ratio [OR] 1.00, 95% confidence interval [CI] .30-3.34), in total volume of blood loss (median 4500 mL, interquartile range [IQR] 3600-5400) for balloon vs 4000 mL (IQR 3250-5000) for embolization, P = 0.382) or in total units of packed red blood cells transfused (median 7 (IQR 5-10) for balloon vs 6 [IQR 4-9] for embolization, P = 0.319). Fifteen women (30%) who were initially managed by an intrauterine balloon still underwent uterine artery embolization, of whom one had an embolization-related thrombo-embolic event. Maternal mortality occurred in neither of the intervention groups. CONCLUSIONS: No difference in the risk of peripartum hysterectomy and/or maternal death was observed between women who had intrauterine balloon tamponade and women who underwent uterine artery embolization as an initial management for persistent postpartum hemorrhage. Although this study was underpowered to demonstrate equivalence, our study design provides a framework for future research in which intrauterine balloon tamponade may prove to be a suitable intervention of first choice in the management of persistent postpartum hemorrhage.

Comparison of thromboelastometry by ROTEM® Delta and ROTEM® Sigma in women with postpartum haemorrhage.

Haemostatic treatment in women experiencing postpartum haemorrhage is increasingly based on point-of-care devices such as ROTEM® thromboelastometry. Recently, a fully automated successor of the ROTEM® Delta device, the ROTEM® Sigma was introduced. To determine whether these devices provide similar results, we compared ROTEM® parameters using the ROTEM® Delta and Sigma devices in women experiencing postpartum haemorrhage. Prospective observational cohort study of 23 women experiencing postpartum haemorrhage. ROTEM® INTEM, EXTEM, FIBTEM and APTEM measurements handled by the ROTEM® Delta and Sigma devices were compared. ROTEM® FIBTEM values were also related to Clauss fibrinogen values. A correlation of Spearman's r (rs) varying between 0.76 and 0.95 was displayed between clot firmness measured in millimeters at 5 (A5), 10 (A10) and 20 (A20) minutes after start of clot formation measured by EXTEM, INTEM and APTEM assays executed on both devices; A5, A10 and A20 of FIBTEM correlated less well (rS between 0.71 and 0.74), especially after five and ten minutes. Correlation between both devices regarding clotting time (CT) was poor. The observed correlation between levels of Clauss fibrinogen and FIBTEM A5 was rs = 0.70, (95% confidence interval (CI): 0.38 to 0.87) for Delta and rs = 0.85, (CI 0.65 to 0.94) for Sigma. A5, A10 and A20 measured in EXTEM, INTEM and APTEM obtained from ROTEM® Delta and Sigma devices were similar. EXTEM, FIBTEM and APTEM CT values from both devices showed no correlation. Substantial variation was found between FIBTEM assays of the devices. Consequently, results of FIBTEM assays should always be interpreted in the context of device-specific reference values. Correlation with Clauss fibrinogen was better in the ROTEM® Sigma device.

Age of platelet concentrates and time to the next transfusion.

BACKGROUND: Storage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia. STUDY DESIGN AND METHODS: From a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for different storage time categories (i.e., fresh, <4 days; intermediate, 4-5 days; and old, >5 days) were estimated, per component type, using multilevel mixed-effects linear models. RESULTS: Among a cohort of 29,761 patients who received 140,896 PLT transfusions we selected 4441 hematooncology patients who had received 12,724 PLT transfusions during periods of PLT transfusion dependency. Transfusion of fresh, compared to old, buffy coat-derived PLTs in plasma was associated with a delay to the next transfusion of 6.2 hours (95% confidence interval [CI], 4.5-8.0 hr). For buffy coat-derived PLTs in PAS-B and -C this difference was 7.7 hours (95% CI, 2.2-13.3 hr) and 3.9 hours (95% CI, -2.1 to 9.9 hr) while for apheresis PLTs in plasma it was only 1.8 hours (95% CI, -3.5 to 7.1 hr). CONCLUSION: Our results indicate that the time to the next transfusion shortens with increasing age of transfused buffy coat-derived PLT concentrates. This association was not observed for apheresis PLTs.

Association between fluid management and dilutional coagulopathy in severe postpartum haemorrhage: a nationwide retrospective cohort study.

BACKGROUND: The view that 2 l of crystalloid and 1.5 l of colloid can be infused while awaiting compatible blood for patients with major postpartum haemorrhage is based on expert opinion documents. We describe real-world changes in levels of coagulation parameters after the administration of different volumes of clear fluids to women suffering from major postpartum haemorrhage. METHODS: We performed a nationwide retrospective cohort study in the Netherlands among 1038 women experiencing severe postpartum haemorrhage who had received at least four units of red cells or fresh frozen plasma or platelets in addition to red cells. The volume of clear fluids administered before the time of blood sampling was classified into three fluid administration strategies, based on the RCOG guideline: < 2 L, 2-3.5 L and > 3.5 L. Outcomes included haemoglobin, haematocrit, platelet count, fibrinogen, aPTT and PT levels. RESULTS: Haemoglobin, haematocrit, platelet count, fibrinogen and aPTT were associated with volumes of clear fluids, which was most pronounced early during the course of postpartum haemorrhage. During the earliest phases of postpartum haemorrhage median haemoglobin level was 10.1 g/dl (IQR 8.5-11.6) among the women who received < 2 L clear fluids and 8.1 g/dl (IQR 7.1-8.4) among women who received > 3.5 L of clear fluids; similarly median platelet counts were 181 × 109/litre (IQR 131-239) and 89 × 109/litre (IQR 84-135), aPTT 29 s (IQR 27-33) and 38 s (IQR 35-55) and fibrinogen 3.9 g/L (IQR 2.5-5.2) and 1.6 g/L (IQR 1.3-2.1). CONCLUSIONS: In this large cohort of women with severe postpartum haemorrhage, administration of larger volumes of clear fluids was associated with more severe deterioration of coagulation parameters corresponding to dilution. Our findings provide thus far the best available evidence to support expert opinion-based guidelines recommending restrictive fluid resuscitation in women experiencing postpartum haemorrhage. TRIAL REGISTRATION: Netherlands Trial Register ( NTR4079 ), registration date July 17, 2013.

Association of Blood Transfusion From Female Donors With and Without a History of Pregnancy With Mortality Among Male and Female Transfusion Recipients.

Importance: Transfusion of red blood cells from female donors has been associated with increased mortality in male recipients. Objective: To quantify the association between red blood cell transfusion from female donors with and without a history of pregnancy and mortality of red blood cell recipients. Design, Setting, and Participants: Retrospective cohort study of first-time transfusion recipients at 6 major Dutch hospitals enrolled from May 30, 2005, to September 1, 2015; the final follow-up date was September 1, 2015. The primary analysis was the no-donor-mixture cohort (ie, either all red blood cell transfusions exclusively from male donors, or all exclusively from female donors without a history of pregnancy, or all exclusively from female donors with a history of pregnancy). The association between mortality and exposure to transfusions from ever-pregnant or never-pregnant female donors was analyzed using life tables and time-varying Cox proportional hazards models. Exposures: Red blood cell transfusions from ever-pregnant or never-pregnant female donors, compared with red blood cell transfusions from male donors. Main Outcomes and Measures: All-cause mortality during follow-up. Results: The cohort for the primary analyses consisted of 31 118 patients (median age, 65 [interquartile range, 42-77] years; 52% female) who received 59 320 red blood cell transfusions exclusively from 1 of 3 types of donors (88% male; 6% ever-pregnant female; and 6% never-pregnant female). The number of deaths in this cohort was 3969 (13% mortality). For male recipients of red blood cell transfusions, all-cause mortality rates after a red blood cell transfusion from an ever-pregnant female donor vs male donor were 101 vs 80 deaths per 1000 person-years (time-dependent "per transfusion" hazard ratio [HR] for death, 1.13 [95% CI, 1.01-1.26]). For receipt of transfusion from a never-pregnant female donor vs male donor, mortality rates were 78 vs 80 deaths per 1000 person-years (HR, 0.93 [95% CI, 0.81-1.06]). Among female recipients of red blood cell transfusions, mortality rates for an ever-pregnant female donor vs male donor were 74 vs 62 per 1000 person-years (HR, 0.99 [95% CI, 0.87 to 1.13]); for a never-pregnant female donor vs male donor, mortality rates were 74 vs 62 per 1000 person-years (HR, 1.01 [95% CI, 0.88-1.15]). Conclusions and Relevance: Among patients who received red blood cell transfusions, receipt of a transfusion from an ever-pregnant female donor, compared with a male donor, was associated with increased all-cause mortality among male recipients but not among female recipients. Transfusions from never-pregnant female donors were not associated with increased mortality among male or female recipients. Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism.

Most major bleeds in preterm infants occur in the absence of severe thrombocytopenia: an observational cohort study.

OBJECTIVE: To describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding. DESIGN: Observational cohort study. SETTING: A Dutch tertiary care neonatal intensive care unit. PATIENTS: All consecutive infants with a gestational age at birth <32 weeks admitted between January 2004 and July 2022. EXPOSURE: Infants were stratified into nine groups based on their nadir platelet count (×109/L) during admission (<10, 10-24, 25-49, 50-99, 100-149, 150-199, 200-249, 250-299 and ≥300), measured before the diagnosis of a major bleed and before any platelet transfusion was administered. MAIN OUTCOME MEASURE: Incidence of major bleeds during admission. Logistic regression analysis was used to quantify the relationship between nadir platelet count and incidence of major bleeds. RESULTS: Among 2772 included infants, 224 (8%) developed a major bleed. Of the infants with a major bleed, 92% (206/224) had a nadir platelet count ≥50×109/L. The incidence of major bleeds was 8% among infants with and without severe thrombocytopenia (platelet count <50×109/L), 18/231 (95% CI 5 to 12) and 206/2541 (95% CI 7 to 9), respectively. Similarly, after adjustment for measured confounders, there was no notable association between nadir platelet counts below versus above 50×109/L and the occurrence of major bleeds (OR 1.09, 95% CI 0.61 to 1.94). CONCLUSION: In very preterm infants, the vast majority of major bleeds occur in infants without severe thrombocytopenia.