A UK national survey of prophylactic platelet transfusion thresholds in non-bleeding, critically ill adults

Thrombocytopaenia is common in critically ill patients and associated with poor clinical outcomes. Current guideline recommendations for prophylactic platelet transfusions, to prevent bleeding in critically ill patients with thrombocytopaenia, are based on observational data. Recent studies conducted in non-critically ill patients have demonstrated harm associated with platelet transfusions and have also called into question the efficacy of platelet transfusion. To date, there are no well-conducted randomised controlled trials (RCTs) evaluating platelet transfusion in critically ill patients. To inform the design of such an RCT, we sought to characterise current clinical practice across four commonly encountered scenarios in non-bleeding critically ill adult patients with thrombocytopaenia. An online survey link was sent to Clinical Directors and contacts of all adult general ICUs participating in the Intensive Care National Audit and Research Centre Case Mix Programme national clinical audit (n=200). The survey collected data regarding the respondents place of work, training grade and their current individual practice and possible limits of equipoise for prescribing prophylactic platelet transfusions across four scenarios: prophylaxis but with no procedure planned (NPP); ultrasound guided insertion of a right internal jugular central venous catheter (JVI); percutaneous tracheostomy (PT); and surgery with a low bleeding risk (SLBR). After excluding nine responses with missing data on all four of the main questions, responses were received from 99 staff, covering 78 ICUs (39.0% of 200 ICUs invited to participate). While nearly all respondents (98.0%) indicated a platelet transfusion threshold of 30 x 10^9/L or less for patients with no planned procedure, thresholds for planned procedures varied widely and centred at medians of 40 x 10^9/L for JVI (range: 10 to 70), 50 x 10^9/L for SLBR (range: 10 to 100) and 70 x 10^9/L for PT (range: 20 to greater than 100). Current platelet transfusion practice in UK ICUs prior to invasive procedures with relatively low bleeding risks is highly variable. Well-designed studies are needed to determine the optimal platelet transfusion thresholds in critical care.

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Transfusion practice in the non-bleeding critically ill: an international online survey—the TRACE survey

Critical Care ◽

10.1186/s13054-019-2591-6 ◽

2019 ◽

Vol 23 (1) ◽

Cited By ~ 8

Author(s):

Sanne de Bruin ◽

◽

Thomas W. L. Scheeren ◽

Jan Bakker ◽

Robin van Bruggen ◽

...

Keyword(s):

Blood Cell ◽

Critically Ill ◽

Red Blood Cell ◽

Critically Ill Patients ◽

Online Survey ◽

Transfusion Practice ◽

Red Blood Cell Transfusion ◽

Plasma Transfusion ◽

Transfusion Threshold ◽

Asymptomatic Patients

Abstract Background Over the last decade, multiple large randomized controlled trials have studied alternative transfusion strategies in critically ill patients, demonstrating the safety of restrictive transfusion strategies. Due to the lack of international guidelines specific for the intensive care unit (ICU), we hypothesized that a large heterogeneity in transfusion practice in this patient population exists. The aims of this study were to describe the current transfusion practices and identify the knowledge gaps. Methods An online, anonymous, worldwide survey among ICU physicians was performed evaluating red blood cell, platelet and plasma transfusion practices. Furthermore, the presence of a hospital- or ICU-specific transfusion guideline was asked. Only completed surveys were analysed. Results Nine hundred forty-seven respondents filled in the survey of which 725 could be analysed. Hospital transfusion protocol available in their ICU was reported by 53% of the respondents. Only 29% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin (Hb) threshold for the general ICU population was 7 g/dL (7–7). The highest reported variation in transfusion threshold was in patients on extracorporeal membrane oxygenation or with brain injury (8 g/dL (7.0–9.0)). Platelets were transfused at a median count of 20 × 109 cells/L IQR (10–25) in asymptomatic patients, but at a higher count prior to invasive procedures (p < 0.001). In patients with an international normalized ratio (INR) > 3, 43% and 57% of the respondents would consider plasma transfusion without any upcoming procedures or prior to a planned invasive procedure, respectively. Finally, doctors with base specialty in anaesthesiology transfused critically ill patients more liberally compared to internal medicine physicians. Conclusion Red blood cell transfusion practice for the general ICU population is restrictive, while for different subpopulations, higher Hb thresholds are applied. Furthermore, practice in plasma and platelet transfusion is heterogeneous, and local transfusion guidelines are lacking in the majority of the ICUs.

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Transfusion Practice Following Intracranial Hemorrhage in Acute Leukemia: An Institutional Review

Blood ◽

10.1182/blood-2018-99-112718 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4740-4740

Author(s):

Shannon Nixon ◽

Dawn Maze ◽

Eshetu G Atenafu ◽

Danielle Brandys ◽

Cindy Susan Murray ◽

...

Keyword(s):

Platelet Count ◽

Retrospective Study ◽

Acute Leukemia ◽

Intracranial Hemorrhage ◽

Platelet Transfusion ◽

Transfusion Practice ◽

Rank Test ◽

Transfusion Threshold ◽

Platelet Counts ◽

Platelet Transfusions

Abstract Background: Intracranial hemorrhage (ICH) is a common complication in acute leukemia that is associated with significant morbidity and mortality. While evidence supports prophylactic platelet transfusions at a threshold < 10 x 109/L to reduce the risk of bleeding in acute leukemia, there is little data to guide platelet transfusion practice in patients following ICH. The objectives of this study were to characterize the clinical features and outcomes of acute leukemia patients with ICH and to understand current platelet transfusion practice following ICH. Methods: This was a retrospective study conducted at a large, quaternary, academic cancer centre. We included all adult patients with a diagnosis of acute leukemia who had a documented ICH at our centre between January 1, 2009 and December 31, 2016. We assessed demographics, medications, infection and bleeding history in the week preceding ICH, characteristics of ICH including site of bleed, acute management, transfusion practice in the first 90 days, and clinical outcomes. Radiologic scans were re-assessed by neuroradiology to determine if the ICH was stable or if new or progressive bleeding had developed. Transfusion practice following the ICH was compared between the two groups with longitudinal data analysis using platelet counts as outcome. Kaplan-Meier product limit method was used to estimate overall survival (OS) rates as well as to obtain median survival; log-rank test was used to compare OS among those without new or progressive ICH vs. those with progression. Results: During the study period, of 2576 patients diagnosed with acute leukemia, 101 suffered from ICH and were included in the study. Most patients (94) had AML, of which 9 had APL, 6 had ALL, and 1 had MPAL. At the time of ICH, 61 patients were newly diagnosed or receiving induction chemotherapy, 33 had relapsed disease and 7 were in complete remission. Spontaneous ICH occurred in 76 patients. Within the week preceding ICH, 7 patients were on medications known to increase bleeding risk and 39 were on tranexamic acid. Sixty-four patients had clinical evidence of bleeding elsewhere and 22 had evidence of infection. On the day of ICH, the median platelet count was 16 x 109/L (range 0- 433 x109/L). Thirty-one patients had a platelet count < 10 x 109/L and 10 of these patients received a platelet transfusion prior to the bleed. Seventy patients had a platelet count ≥10 x109/L and 17 of these received a platelet transfusion prior to the bleed. Six patients (6%) exhibited evidence of platelet transfusion refractoriness. In the 90 days following ICH, 21% of platelet transfusions were given for a platelet count < 10 x 109/L, 55% were given with a platelet count between 10-29 x109/L, and 24% were given with a platelet count ≥ 30 x 109/L. New or progressive ICH occurred in 28 patients. The median platelet transfusion threshold was 19 x 109/L (range 0-114 x 109/L) for those without new or progressive ICH and 21 x 109/L (range 0-93 x 109/L) for those with progression (p=0.04; Figure 1). Of the 101 study patients, 79 have died. Median OS was 5.6 months for those without new or progressive ICH and 2.9 months for those with progression (p=0.002) (Figure 2). Cause of death was attributed to non-ICH causes in the majority of patients 65/79 (82%). Conclusions: In this retrospective study, we evaluated the outcomes of 101 patients with acute leukemia and ICH. At the time of the bleed, the majority of patients had active disease and more than two thirds had platelet counts of 10 x 109/L or higher. During 90 days of follow-up, nearly one third of patients developed new or progressive ICH. Platelet transfusion practice was variable and the median threshold was, in fact, higher in those who subsequently developed new or progressive bleeding. The reasons for this were unclear from our chart review, but we hypothesize that these patients may have had additional risk factors, e.g. fever, infection. The outcomes of patients with acute leukemia and ICH are poor. Factors other than platelet transfusion threshold likely contribute to secondary ICH events and the overall poor prognosis. Disclosures Maze: Novartis: Consultancy, Honoraria.

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The Effect of Platelet Transfusion on Death in the Intensive Care Unit

Blood ◽

10.1182/blood.v128.22.3850.3850 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3850-3850 ◽

Cited By ~ 1

Author(s):

Donald M. Arnold ◽

Shuoyan Ning ◽

Rebecca Barty ◽

Yang Liu ◽

Richard Cook ◽

...

Keyword(s):

Intensive Care Unit ◽

Cardiac Surgery ◽

Intensive Care ◽

Critically Ill ◽

Critically Ill Patients ◽

Research Funding ◽

Platelet Transfusion ◽

Oncology Patients ◽

Risk Of Death ◽

Platelet Transfusions

Abstract Background: Thrombocytopenia is a common complication of critical illness and an independent risk factor for death in the intensive care unit (ICU). Whether platelet transfusions modify the risk of death in critically ill patients is unknown. Methods: Adult patients admitted to ICU who received one or more platelet transfusion over a 10-year period (2006 - 2015) from 3 academic hospitals in Canada were analyzed from a blood transfusion registry. Oncology patients were excluded. Contemporaneous non-transfused ICU patients were used as controls. Data from the registry were validated by integrity checks with medical records and laboratory information systems. We estimated the effect of platelet transfusion on mortality in ICU adjusted for baseline and time-varying covariates including multi-organ dysfunction score (MODS) and severity of thrombocytopenia using a stratified cox proportional hazards model. Significance was set at p<0.05 for all analyses. Results: Of 43,234 non-oncology patients admitted to ICU, 5,621 (13.0%) received one or more platelet transfusion. Compared with non-transfused controls, transfused patients had lower platelet counts (median, 82 x109/L vs. 163 x109/L); were more often admitted after surgery (90.7% vs. 46.9%) especially cardiac surgery (86.8% of surgeries vs. 60.6%); and had higher unadjusted mortality (10.7% vs. 6.5%). Using regression analysis adjusted for covariates (nadir platelet count, red blood cell transfusion, need for hemodialysis) and stratified by age, baseline MODS score (available for 66.2% of patients) and need for invasive mechanical ventilation, platelet transfusions were associated with a lower risk of death in ICU [hazard ratio (HR)= 0.66; 95% confidence interval (CI), 0.46 - 0.96; p= 0.028; n= 26,404 with all available data]. A similar effect was observed in the subgroup of cardiac surgery patients (HR= 0.50; 95% CI, 0.26 - 0.98; p=0.044; n= 10,676) but not all surgical patients (HR = 0.73; 95% CI, 0.46 - 1.17; p= 0.188; n= 14,461). Conclusion:After adjusting for illness severity, thrombocytopenia and other confounders common among critically ill patients, platelet transfusions were associated with improved survival in the population of mostly cardiac surgery patients. This potential protective effect of platelet transfusions requires further evaluation in prospective studies. Disclosures Arnold: Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; UCB: Consultancy; Amgen: Consultancy, Research Funding.

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Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?*

Critical Care Medicine ◽

10.1097/00003246-200109001-00007 ◽

2001 ◽

Vol 29 (Supplement) ◽

pp. S181-S188 ◽

Cited By ~ 1

Author(s):

Paul C. Hébert ◽

Elizabeth Yetisir ◽

Claudio Martin ◽

Morris A. Blajchman ◽

George Wells ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Critically Ill ◽

Critically Ill Patients ◽

Transfusion Threshold

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Platelet transfusions for critically ill patients with thrombocytopenia

Blood ◽

10.1182/blood-2013-02-435693 ◽

2014 ◽

Vol 123 (8) ◽

pp. 1146-1151 ◽

Cited By ~ 50

Author(s):

Lani Lieberman ◽

Rachel S. Bercovitz ◽

Naushin S. Sholapur ◽

Nancy M. Heddle ◽

Simon J. Stanworth ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Platelet Transfusions

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Blood product therapy in the ICU

10.1093/med/9780199600830.003.0267 ◽

2016 ◽

Author(s):

Lirong Qu ◽

Darrell J. Triulzi

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Large Body ◽

Invasive Procedure ◽

Transfusion Practice ◽

Transmission Risk ◽

Haemostatic Agents ◽

Circulatory Overload ◽

Red Cell Transfusion ◽

Transfusion Guidelines

Transfusions are among the most common medical procedures in the intensive care unit. Several randomized controlled trials (RCT) indicate that restrictive red cell transfusion practice using a haemoglobin of <7g/dL is safe in critically-ill patients. Although similar RCT are not available for plasma or platelet transfusion guidelines, a large body of observational studies suggest that plasma transfusion for an invasive procedure has not been shown to be of benefit in patients with INR <2.0. Similarly, in thrombocytopenic patients, the target platelet count for bleeding or for an invasive procedure is 50,000/µl. Viral transmission risk has become exceedingly low. Other risks such as transfusion-associated circulatory overload and, to a lesser extent, transfusion-related acute lung injury, are much more common. Storage of red cells does not seem to be associated with adverse clinical outcomes. Alternatives using haemostatic agents, salvaged blood, and adherence to evidence-based transfusion guidelines probably reduce the need for transfusion in critically-ill patients.

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How well do platelets prevent bleeding?

Hematology ◽

10.1182/hematology.2020000136 ◽

2020 ◽

Vol 2020 (1) ◽

pp. 518-522

Author(s):

Darrell J. Triulzi

Keyword(s):

Platelet Transfusion ◽

Anticoagulation Therapy ◽

Outpatient Setting ◽

Severe Thrombocytopenia ◽

Transfusion Threshold ◽

Spontaneous Bleeding ◽

Risk Of Bleeding ◽

Increased Risk ◽

High Incidence ◽

Platelet Transfusions

Abstract Prophylactic platelet transfusions are used to reduce the risk of spontaneous bleeding in patients with treatment- or disease-related severe thrombocytopenia. A prophylactic platelet-transfusion threshold of <10 × 103/µL has been shown to be safe in stable hematology/oncology patients. A higher threshold and/or larger or more frequent platelet doses may be appropriate for patients with clinical features associated with an increased risk of bleeding such as high fevers, sepsis, disseminated intravascular coagulation, anticoagulation therapy, or splenomegaly. Unique factors in the outpatient setting may support the use of a higher platelet-transfusion threshold and/or dose of platelets. A prophylactic platelet-transfusion strategy has been shown to be associated with a lower risk of bleeding compared with no prophylaxis in adult patients receiving chemotherapy but not for autologous transplant recipients. Despite the use of prophylactic platelet transfusions, a high incidence (50% to 70%) of spontaneous bleeding remains. Using a higher threshold or larger doses of platelets does not change this risk. New approaches to reduce the risk of spontaneous bleeding, including antifibrinolytic therapy, are currently under study.

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A Multi-Centre Prospective Observational Study of Platelet Transfusion Practice in Neonates with Severe Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.961.961 ◽

2006 ◽

Vol 108 (11) ◽

pp. 961-961 ◽

Cited By ~ 4

Author(s):

Neil Murray ◽

Sally Ballard ◽

Angela Casbard ◽

Mike Murphy ◽

Irene Roberts ◽

...

Keyword(s):

Observational Study ◽

Major Bleeding ◽

Platelet Transfusion ◽

Transfusion Practice ◽

Major Haemorrhage ◽

Study Entry ◽

Severe Thrombocytopenia ◽

Minor Bleeding ◽

Grade 3 ◽

Platelet Transfusions

Abstract Background: Platelet transfusion practice in neonates is not evidence-based and there is a lack of data relating transfusion to clinical outcome. To inform the design of clinical trials, we conducted a prospective multicentre observational study of platelet transfusion in thombocytopenic neonates to describe: transfusion practice, including reason for transfusion; clinically-related outcomes, including minor and major bleeding and mortality. Methods: Neonates with platelets <60x109/l were studied at 7 UK neonatal intensive care units Mar 05-Jun 06. With parental consent, daily data were collected on minor bleeding (blood staining of oral/nasogastric/endotracheal secretions and stool; microscopic haematuria; petechial rash; oozing from puncture sites - scored 0–7), and major bleeding (intraventricular (IVH), intra-abdominal, pulmonary or renal). Surviving neonates were studied for 7 days or until platelets were ≥60x109/l. Blood counts and all transfusions were directed by the attending neonatologist, with reason for transfusion and its effect on bleeding prospectively documented. Results: 145 of 167 (87%) eligible neonates were enrolled; 123 (85%) were < 37 weeks gestational age (GA), 89 (61%) were male. The study documented 186 episodes of thrombocytopenia (1606 study days) and 309 platelet transfusions given to 91 (63%) neonates. GA, birth weight and age at thrombocytopenic episode were: 27 (24–32) weeks; 825 (675–1370) grams; 5 (2–16) days, respectively [all data median (IQR)]. 21/145 babies (14%) had major IVH (Grade 3/4) at study entry. Platelets (x 109/l) at study entry, and at platelet nadir, and duration of count <60x109/l were: 44 (33–54); 31 (19–42); 2 (1–5) days respectively. In transfused neonates, platelets (x109/l) pre- and post-transfusion, and number of transfusions were: 27 (19–36); 84 (46–138); 2 (1–4) respectively. The principal indications for transfusion were:- platelet count below threshold of unit guideline: 265/309 (86%); deteriorating clinical condition: 17/309 (6%); and significant bleeding: 7/309 (2%). At least 1 episode of minor bleeding was recorded on 622/1606 (39%) of study days. Minor bleeding scores recorded for 12 hours pre- and post each transfusion were [median (IQR)]: 1 (0–2) and 0 (0–1) respectively. New or extension of IVH bleeding to Grade 3/4 occurred in 7 neonates and other major haemorrhage in 9 neonates (4 pulmonary, 3 GI). A total of 20/145 (14%) neonates died, 13 with major IVH bleeding (of which 10 had Grade 3/4 IVH at study entry); all received platelet transfusions [total 87; median 3 (2 to 7). Conclusion: This study confirms that most neonates with severe thrombocytopenia are preterm, most episodes develop after 72 hours of life (median 5 days) and are of short duration (median 2 days). Minor haemorrhage is common and may be reduced by platelet transfusion. Major haemorrhage is uncommon (11%), is associated with mortality (82%) and affected patients receive a large number of platelet transfusions. There is a clear distinction between the majority of thrombocytopenic neonates who receive one or two transfusions as prophylaxis with a good outcome, and the minority who suffer adverse outcomes despite transfusion. Many neonates are transfused with platelets at thresholds below those suggested in guidelines without apparent clinical detriment. These data will be invaluable for planning the randomised trials necessary for rationalising platelet transfusion in these vulnerable patients.

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Platelet Transfusion Thresholds In Neonates: Substantial Differences Between U.S. and Europe

Blood ◽

10.1182/blood.v116.21.3356.3356 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3356-3356

Author(s):

Malte MD Cremer ◽

Martha Sola-Visner ◽

Stephanie Roll ◽

Cassandra Josephson ◽

Zeynep Yilmaz ◽

...

Keyword(s):

Platelet Transfusion ◽

Term Infant ◽

Odds Ratios ◽

Case Scenario ◽

Transfusion Threshold ◽

Mortality And Morbidity ◽

The Us ◽

Level 1 ◽

International Comparative ◽

Platelet Transfusions

Abstract Abstract 3356 Background: Thrombocytopenia affects 20–35% of patients admitted to Neonatal Intensive Care Units (NICUs). Platelet transfusions are usually administered to thrombocytopenic neonates at higher thresholds than those used for older children or adults, although there is a paucity of evidence to guide these decisions. Methods: In this study, we used a web-based survey to investigate the platelet transfusion thresholds used in level 1 NICUs (equivalent to level 3 in the US) in German-speaking European countries (Austria, Germany and Switzerland, AUT/GER/SUI). This survey was identical to the one previously used to investigate the transfusion practices of US neonatologists, thus allowing for a direct comparison of both populations. Eleven common clinical case scenarios of thrombocytopenia in preterm or term neonates were described and neonatologists were asked at which platelet count they would order a transfusion. For each case scenario, the median and the most frequently selected thresholds were determined. The Mann-Whitney-U-test was applied to compare the distribution of platelet transfusion thresholds between AUT/GER/SUI and US neonatologists. Univariate cumulative logit models (proportional odds model) were used to evaluate the differences between AUT/GER/SUI and US practices. In this analysis, an odds ratio >1 indicates an increased odd to select a higher threshold. Results: At least one neonatologist from 100 of the 171 (58%) eligible level 1 NICUs (AUT n=2; GER n=92; SUI n=6) participated in the survey, for a total of 144 neonatologists. Their answers were compared with those of 1006 U.S. neonatologists previously surveyed. In 9 of the 11 scenarios, AUT/GER/SUI neonatologists selected substantially lower platelet transfusion thresholds than US neonatologists (P<.0001). For example, in a preterm infant (27 weeks of gestation and 950g) who was clinically stable and not bleeding at two days of life, the median platelet transfusion threshold was 30×109/L in AUT/GER/SUI vs. 50×109/L in the US (P<.0001). If the same infant had an intracranial hemorrhage, the most frequent threshold among AUT/GER/SUI neonatologists increased to 50×109/L, while most US neonatologists rose their trigger to 100×109/L (P<.0001). To quantify the differences in transfusion practices between the two groups of physicians, we then calculated (for each case scenario) the odds of US neonatologists selecting a higher transfusion category than their European colleagues. In nine of the eleven scenarios the odds ratios were between 3.25 and 5.05, reflecting the high likelihood that a US neonatologist would choose a higher transfusion threshold than an AUT/GER/SUI neonatologist facing the same patient. Only in two case scenarios (term infant with alloimmune thrombocytopenia and premature infant prior to lumbar puncture) the odds ratios were <2, reflecting more similar (although still significantly different) responses. Finally, in order to estimate the clinical impact of the observed differences, we recorded the platelet counts of every neonate admitted to our NICU over a six month period, and determined whether they would receive a platelet transfusion by extrapolating the answers of AUT/GER/SUI vs. US neonatologists to the first clinical vignette. Using this approach, we estimated that 18 out of 1000 neonates would be transfused if AUT/GER/SUI patterns were applied, compared to 33 transfused infants if US patterns were applied (1.8-fold increase). Conclusion: This first international comparative survey on platelet transfusion practices in neonates revealed substantially higher transfusion thresholds in the US than in AUT/GER/SUI. These differences might have substantial clinical implications, since platelet transfusions are associated with higher neonatal mortality and morbidity. In neonates with necrotizing enterocolitis and thrombocytopenia, receiving a higher number of platelet transfusions has been associated with a higher incidence of short bowel syndrome and cholestasis, and there is evidence to support the hypothesis that platelet transfusions can worsen bowel injury. Thus, well-designed clinical studies are needed to address the risks/benefits of these different approaches. Disclosures: Josephson: Immucor: Speakers Bureau.

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