Background and ObjectivesDonor characteristics have been implicated in transfusion-related adverse events. Uncertainty remains about whether sex, and specifically pregnancy history of the blood... Show moreBackground and ObjectivesDonor 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 MethodsWe 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.ResultsThe 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.ConclusionThese findings do not consistently support the notion that the observed association between ever-pregnant donor units and mortality is mediated by blood product storage. Show less
Background: The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing.Objectives:... Show moreBackground: The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing.Objectives: We aimed to describe the CVD risk score of PwH according to Pooled Cohort Equations Risk (PCER) Calculator tool and its treatment recommendations. We also compared the PCER estimates with the respective Framingham Risk Score (FRS).Methods: This cross-sectional study included male PwH = 40 years treated at the Comprehensive Haemophilia Treatment Centre of Pernambuco (Recife/Brasil). PwH with a previous CVD event or a low-density lipid cholesterol = 5.0 mmol/L were excluded. Interviews, medical file reviews, and blood tests were performed. The PCER tool was used to estimate the CVD risk and compare it with the respective FRS. A p-value < 0.05 was accepted as statistically significant.Results: Thirty PwH were included. Median age was 51.5 [interquartile range-IQR; 46.0-59.5] years. The prevalence of obesity, systemic arterial hypertension, diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, and hypoHDLaemia were 20%, 67%, 24%, 14%, 47%, and 23%, respectively. The median PCER score was 6.9% [IQR; 3.1-13.2], with 50% having a high risk (PCER = 7.5%). Statin use was suggested for 54% of PwH. Blood pressure was poorly controlled in 47% of PwH. The agreement between PCER and FRS was 80% (? = 0.60; p = 0.001).Conclusions: Half of the male people with haemophilia aged 40 years or older had a 10-year high risk of developing CVD with strong recommendations to improve control of dyslipidaemia and blood pressure. Show less
Vos, T.W. de; Winkelhorst, D.; Arnadottir, V.; Bom, J.G. van der; Suris, C.C.; Caram-Deelder, C.; ... ; Lopriore, E. 2022
Background Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence... Show moreBackground Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence. We aimed to describe the contemporary management and outcomes of patients with FNAIT in high-income countries.Methods In this multicentre, retrospective, cohort study, we set up a web-based registry for the collection of deidentified data on the management and course of neonates with FNAIT. Eight centres from seven countries (Australia, Norway, Slovenia, Spain, Sweden, the Netherlands, and the USA) participated. Eligibility criteria comprised neonates with FNAIT being liveborn between Jan 1, 2010, and Jan 1, 2020; anti-human platelet antigen (HPA) alloantibodies in maternal serum; confirmed maternal and fetal HPA incompatibility; and bleeding detected at antenatal ultrasound, neonatal thrombocytopenia (<150 x 10(9) platelets per L), or both in the current or previous pregnancy. Clinical data were retrieved from local medical records of the first neonatal admission and entered in the registry. The key outcome was the type of postnatal treatment given to neonates with FNAIT. Other outcomes were daily median platelet counts in the first week of life, median platelet count increment after first unmatched versus first matched transfusions, and the proportion of neonates with mild or severe bleeding.Findings 408 liveborn neonates with FNAIT were entered into the FNAIT registry, of whom 389 from Australia (n=74), Norway (n=56), Slovenia (n=19), Spain (n=55), Sweden (n=31), the Netherlands (n=138), and the USA (n=16) were included in our analyses. The median follow-up was 5 days (IQR 2-9). More neonates were male (241 [64%] of 379) than female (138 [36%]). Severe thrombocytopenia (platelet count <50 x 10(9) platelets per L) was reported in 283 (74%) of 380 neonates, and extreme thrombo-cytopenia (<10 x 10(9) platelets per L) was reported in 92 (24%) neonates. Postnatal platelet count nadir was higher in the no-treatment group than in all other groups. 163 (42%) of 389 neonates with FNAIT received no postnatal treatment. 207 (53%) neonates received platelet transfusions, which were either HPA-unmatched (88 [43%] of 207), HPA-matched (84 [41%]), or a combination of both (35 [17%]). The proportion of neonates who received HPA-matched platelet transfusions varied between countries, ranging from 0% (Slovenia) to 63% (35 of 56 neonates; Norway). Postnatal intravenous immunoglobulin treatment was given to 110 (28%) of 389 neonates (alone [n=19] or in combination with platelet transfusions [n=91]), with the proportion receiving it ranging from 12% (17 of 138 neonates; the Netherlands) to 63% (ten of 16 neonates; the USA) across countries. The median platelet increment was 59 x 10(9) platelets per L (IQR 35-94) after HPA-unmatched platelet transfusions and 98 x 10(9) platelets per L (67-134) after HPA-matched platelet transfusions (p<0 center dot 0001). Severe bleeding was diagnosed in 23 (6%) of 389 liveborn neonates, with one having a severe pulmonary haemorrhage and 22 having severe intracranial haemorrhages. Mild bleeding was diagnosed in 186 (48%) neonates.Interpretation Postnatal management of FNAIT varies greatly between international centres, highlighting the absence of consensus on optimal treatments. Our data suggest that HPA-matched transfusions lead to a larger median platelet count increment than HPA-unmatched transfusions, but whether HPA matching is also associated with a reduced risk of bleeding remains unknown. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Background Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and... Show moreBackground Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI ( increment t(inhi-ITI)) is debatable. Objective The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6-8.1) and 6.9 years [IQR, 2.6-20.1), respectively. PwHA-HRi were stratified according to increment t(inhi-ITI) quartiles: first (0.0-0.6 year), second (>0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start. Show less
Kranenburg, F.J.; Arbous, S.M.; Caram-Deelder, C.; Putter, H.; Cessie, S. le; Bom, J.G. van der 2022
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... Show moreBackground 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. Show less
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... Show moreBackground: 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. Show less
Tahitu, M.; Ramler, P.I.; Gillissen, A.; Caram-Deelder, C.; Henriquez, D.D.C.A.; Maat, M.P.M. de; ... ; Bom, J.G. van der 2021
Introduction: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of... Show moreIntroduction: 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 (R)) 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. Show less
Cornelissen, L.L.; Caram-Deelder, C.; Fustolo-Gunnink, S.F.; Groenwold, R.H.H.; Stanworth, S.J.; Zwaginga, J.J.; Bom, J.G. van der 2021
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... Show moreBackground 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. Show less
Ramler, P.I.; Gillissen, A.; Henriquez, D.D.C.A.; Caram-Deelder, C.; Markovski, A.A.; Maat, M.P.M. de; ... ; Bom, J.G. van der 2021
Introduction To evaluate rotational fibrin-based thromboelastometry (ROTEM(R) FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to... Show moreIntroduction To evaluate rotational fibrin-based thromboelastometry (ROTEM(R) 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. Show less
Camelo, R.M.; Caram-Deelder, C.; Duarte, B.P.; Moura, M.C.B. de; Costa, N.C.D.; Costa, I.M.; ... ; Bom, J. van der 2021
Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related... Show moreSince the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients >= 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0-51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years. Show less
Cornelissen, L.L.; Caram-Deelder, C.; Fustolo-Gunnink, S.F.; Groenwold, R.H.H.; Stanworth, S.J.; Zwaginga, J.J.; Bom, J.G. van der 2021
Background: Prophylactic platelet transfusions prevent bleeding in hematooncology patients, but it is unclear how any benefit varies between patients. Our aim was to assess if patients with... Show moreBackground: Prophylactic platelet transfusions prevent bleeding in hematooncology 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 Show less
Cornelissen, L.L.; Caram-Deelder, C.; Meier, R.T.; Zwaginga, J.J.; Evers, D.; Dutch Blood Transfusion Related R 2020
Objectives There is scarce evidence about the effectiveness of anti-bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical... Show moreObjectives 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. Show less
Cornelissen, L.L.; Kreuger, A.L.; Caram-Deelder, C.; Middelburg, R.A.; Kerkhoffs, J.L.H.; Borne, P.A. von dem; ... ; Bom, J.G. van der 2020
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... Show moreWe 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. Show less
Saadah, N.H.; Schipperus, M.R.; Wiersum-Osselton, J.C.; Kraaij, M.G. van; Caram-Deelder, C.; Beckers, E.A.M.; ... ; Bom, J.G. van der 2020
Plasma transfusion is indicated for replenishment of coagulative pro- teins to stop or prevent bleeding. In 2014, the Netherlands switched from using similar to 300mL fresh frozen plasma (FFP)... Show morePlasma transfusion is indicated for replenishment of coagulative pro- teins to stop or prevent bleeding. In 2014, the Netherlands switched from using similar to 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 (similar to 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 (Delta f = f(SD) (-) f(FFP)) in mean plasma/RBC ratio (f) was negligible (Delta f(entire-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. Show less
Introduction Haemato-oncological patients often receive platelet count driven prophylactic platelet transfusions to prevent bleeding. However, many prophylactically transfused patients still bleed.... Show moreIntroduction Haemato-oncological patients often receive platelet count driven prophylactic platelet transfusions to prevent bleeding. However, many prophylactically transfused patients still bleed. More knowledge on risk factors for bleeding is therefore needed. This will enable identification of bleeding risk profiles on which future transfusion policy can be optimised. The present BITE study (Bleeding In Thrombocytopenia Explained) aims to identify clinical conditions and biomarkers that are associated with clinically relevant bleeding events.Methods and analysis A matched case-control study nested in a cohort of haemato-oncological patients in the Netherlands. We collect a limited number of variables from all eligible patients, who together form the source population. These patients are followed for the occurrence of clinically relevant bleeding. Consenting patients of the source population form the cohort. Cases from the cohort are frequency matched to selected control patients for the nested case-control study. Of both case and control patients more detailed clinical data is collected.Study population Adult haemato-oncological patients, who are admitted for intensive chemotherapeutic treatment or stem cell transplantation, or who received such treatments in the past and are readmitted for disease or treatment-related adverse events.Statistical analysis Bleeding incidences will be calculated for the total source population, as well as for different subgroups. The association between potential risk factors and the occurrence of bleeding will be analysed using conditional logistic regression, to account for matching of case and control patients.Ethics and dissemination The study was approved by the Medical Research Ethics Committee Leiden Den Haag and Delft, and the Radboudumc Committee on Research Involving Human Subjects. Approval in seven other centres is foreseen. Patients will be asked for written informed consent and data is coded before analyses, according to Dutch privacy law. Results will be published in peer-reviewed journals. Show less
Ramler, P.I.; Henriquez, D.D.C.A.; Akker, T. van den; Caram-Deelder, C.; Groenwold, R.H.H.; Bloemenkamp, K.W.M.; ... ; TeMpOH-1 Study Grp 2019
Background and ObjectivesThe 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... Show moreBackground and ObjectivesThe 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 MethodsThis 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).ResultsA 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.ConclusionHaemoglobin concentration is the dominant predictor for red cell transfusion. Other clinical characteristics are also predictive, though to a lesser extent. Show less
IMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the... Show moreIMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes.OBJECTIVE To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH.DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019.EXPOSURES Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion.MAIN OUTCOMES AND MEASURES Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization.RESULTS This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results.CONCLUSIONS AND RELEVANCE In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH. Show less
Fustolo-Gunnink, S.F.; Fijnvandraat, K.; Putter, H.; Ree, I.M.; Caram-Deelder, C.; Andriessen, P.; ... ; Bom, J.G. van der 2019
Introduction Incidence of massive transfusion after birth was high in the Netherlands between 2004 and 2006 compared with other high-income countries. This study investigated incidence, causes,... Show moreIntroduction Incidence of massive transfusion after birth was high in the Netherlands between 2004 and 2006 compared with other high-income countries. This study investigated incidence, causes, management and outcome of women receiving massive transfusion due to postpartum hemorrhage in the Netherlands in more recent years. Material and methods Data for all pregnant women who received eight or more units of packed red blood cells from a gestational age of 20 weeks and within the first 24 hours after childbirth, during 2011 and 2012, were obtained from a nationwide retrospective cohort study, including 61 hospitals with a maternity unit in the Netherlands. Results Incidence of massive transfusion due to postpartum hemorrhage decreased to 65 per 100 000 births (95% CI 56-75) between 2011 and 2012, from 91 per 100 000 births (95% CI 81-101) between 2004 and 2006, while median blood loss increased from 4500 mL (interquartile range 3250-6000) to 6000 mL (interquartile range 4500-8000). Uterine atony remained the leading cause of hemorrhage. Thirty percent (53/176) underwent peripartum hysterectomy between 2011 and 2012, compared with 25% (83/327) between 2004 and 2006. Case fatality rate for women who received massive transfusion due to postpartum hemorrhage was 2.3% (4/176) between 2011 and 2012, compared with 0.9% (3/327) between 2004 and 2006. Conclusions The incidence of postpartum hemorrhage with massive transfusion decreased in the Netherlands between both time frames, but remained an important cause of maternal mortality and morbidity, including peripartum hysterectomy. National surveillance of maternal morbidity and mortality due to postpartum hemorrhage through an improved and continuous registration with confidential enquiries may lead to the identification of clear improvements of maternal care. Show less
