scholarly journals The Association Between Platelet Transfusion and Mortality Rate Among Preterm Neonates in the Eastern Province, Saudi Arabia

2021 ◽  
Author(s):  
Fatimah Abdullah Alhamad ◽  
Ahlam Mohammed Hussein ◽  
Friyal Mubarak Alqahtani
Keyword(s):  
Saudi Arabia ◽  
Mortality Rate ◽  
Significant Relationship ◽  
Platelet Transfusion ◽  
Survival Rates ◽  
Preterm Neonates ◽  
High Threshold ◽  
Main Mode ◽  
Transfusion Threshold ◽  
Platelet Transfusions

Platelet transfusion is the main mode of management of thrombocytopenia. However, some studies link frequent and high-threshold platelet transfusions with an incremental increase of mortality rate. Aim: This study aims to assess the association between the frequency and the threshold of platelet transfusions, with the mortality rate among preterm neonates. Methods: A retrospective cohort study design was used. This study was conducted at maternity and children's hospitals in Al-Ahasa, Saudi Arabia. The sample size includes 154 preterm neonates, included in the study by the use of the convenience sampling technique. Result: There is a significant relationship found between the gestational age and the birth weight of the preterm neonates with the survival rates among both groups. In contrast, there is no significant relationship found between transfusion frequency, transfusion threshold, and the survival rates of the group which received platelet transfusion. Implications for Practice and Research: The current study found that mortality is mainly associated with lower gestational ages, and not platelet transfusions. More studies are needed to fill the remaining gaps of knowledge, and to optimise platelet transfusion practices among preterm neonates. Key Words: platelet transfusion, preterm neonate, platelet transfusion threshold, mortality rate.

scholarly journals How well do platelets prevent bleeding?

Hematology ◽  
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.

scholarly journals Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death

Blood ◽  
2019 ◽  
Vol 134 (26) ◽  
pp. 2354-2360
Author(s):  
Susanna F. Fustolo-Gunnink ◽  
Karin Fijnvandraat ◽  
David van Klaveren ◽  
Simon J. Stanworth ◽  
Anna Curley ◽  
...  
Keyword(s):  
Risk Reduction ◽  
Major Bleeding ◽  
Platelet Transfusion ◽  
Risk Group ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Baseline Risk ◽  
Multivariate Logistic Regression Model ◽  
Preterm Neonates ◽  
Transfusion Threshold

Abstract The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25 × 109/L compared with 50 × 109/L for major bleeding and/or mortality in preterm neonates (7% absolute-risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25 × 109/L threshold. We wanted to assess this heterogeneity of treatment effect in the PlaNet-2 trial, to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariate logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into 4 risk quartiles. Within these quartiles, we assessed absolute-risk difference between the 50 × 109/L- and 25 × 109/L-threshold groups. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval, 0.58-0.68). The 25 × 109/L threshold was associated with absolute-risk reduction in all risk groups, varying from 4.9% in the lowest risk group to 12.3% in the highest risk group. These results suggest that a 25 × 109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. This trial was registered at www.isrctn.com as #ISRCTN87736839.

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

Blood ◽  
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.

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

Blood ◽  
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.

scholarly journals Thrombocytopenia, bleeding, and use of platelet transfusions in sick neonates

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 512-516 ◽  
Author(s):  
Simon J. Stanworth
Keyword(s):  
Platelet Count ◽  
Platelet Transfusion ◽  
Survival Rates ◽  
Evidence Base ◽  
Transfusion Practice ◽  
Major Hemorrhage ◽  
Premature Neonates ◽  
Maternal Hypertension ◽  
Neonatal Thrombocytopenia ◽  
Platelet Transfusions

Abstract Survival rates for infants born prematurely have improved significantly, in part due to better supportive care such as RBC transfusion. The role of platelet transfusions in neonates is more controversial. Neonatal thrombocytopenia is common in premature infants. The primary causal factors are intrauterine growth restriction/maternal hypertension, in which the infant presents with thrombocytopenia soon after birth, and sepsis/necrotizing enterocolitis, which are the common morbidities associated with thrombocytopenia in neonates > 72 hours of age. There is no evidence of a relationship between platelet count and occurrence of major hemorrhage, and cardiorespiratory problems are considered the main etiological factors in the development of intraventricular and periventricular hemorrhage in the neonatal period. Platelet transfusions are used commonly as prophylaxis in premature neonates with thrombocytopenia. However, there is widespread variation in the pretransfusion thresholds for platelet count and evidence of marked disparities in platelet transfusion practice between hospitals and countries. Platelet transfusions are biological agents and as such are associated with risks. Unlike other patient groups, specifically patients with hematological malignancies, there have been no recent clinical trials undertaken comparing different thresholds for platelet transfusion in premature neonates. Therefore, there is no evidence base with which to inform safe and effective practice for prophylactic platelet transfusions. There is a need for randomized controlled trials to define the optimal use of platelet transfusions in premature neonates, who at present are transfused heavily with platelets.

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

2020 ◽  
Author(s):  
Akshay Shah ◽  
Doug W Gould ◽  
James C Doidge ◽  
Paul Mouncey ◽  
David A Harrison ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Platelet Transfusion ◽  
Online Survey ◽  
Percutaneous Tracheostomy ◽  
Transfusion Practice ◽  
Research Centre ◽  
Current Guideline ◽  
Transfusion Threshold ◽  
Platelet Transfusions

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.

Platelet Transfusion in Perioperative Medicine

2019 ◽  
Vol 46 (01) ◽  
pp. 050-061
Author(s):  
Thomas Thiele ◽  
Andreas Greinacher
Keyword(s):  
Platelet Function ◽  
Platelet Transfusion ◽  
Point Of Care ◽  
Adverse Outcomes ◽  
Perioperative Medicine ◽  
Transfusion Strategy ◽  
Transfusion Threshold ◽  
Primary Hemostasis ◽  
Weak Evidence ◽  
Platelet Transfusions

AbstractPlatelet transfusions aim to improve primary hemostasis and to prevent or treat bleeding in patients with reduced platelet numbers and/or platelet function. In this review, the authors address the role of platelet transfusions with a focus on perioperative medicine. They summarize different causes of thrombocytopenia in perioperative patients, describe general characteristics and potential adverse effects of different platelet concentrates, describe principles of perioperative platelet transfusion strategies, and highlight specific perioperative scenarios, for example, in patients undergoing antiplatelet therapy. The evidence for any transfusion threshold in perioperative patients based on platelet numbers is low. The evidence supporting prophylactic platelet transfusions in the perioperative setting is very low, and all recommended thresholds for preintervention platelet transfusions are based on weak evidence or expert opinion. Besides the platelet count, platelet function, additional risk factors for bleeding, and the pharmacokinetic properties of concomitant antiplatelet drugs are important criteria for the decision to transfuse or not to transfuse platelets. The few available prospective trials give at least a signal that a liberal platelet transfusion strategy might be associated with poorer outcomes compared with a restrictive platelet transfusion strategy in critically ill patients. Given the unknown risks for adverse outcomes, a therapeutic transfusion strategy during surgery (eventually guided by point of care testing in cardiac surgery, major liver surgery, and major trauma) may be most appropriate for interventions, in which intraoperative bleeding can be controlled until platelets are available, and during the postsurgery period.

scholarly journals 40 Is the New 50: Reducing the Need for Platelet Transfusions Prior to Lumbar Puncture in Patients with Hematologic Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4837-4837
Author(s):  
Kristen M Corrao ◽  
Laura C. Michaelis ◽  
Lisa Baumann Kreuziger ◽  
Karen-Sue B. Carlson ◽  
Sameem Abedin ◽  
...  
Keyword(s):  
Platelet Count ◽  
Lumbar Puncture ◽  
Platelet Transfusion ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Radiology Department ◽  
Oncology Patients ◽  
Transfusion Threshold ◽  
Increased Risk ◽  
Platelet Transfusions

Abstract Introduction: Patients with hematologic malignancies frequently require lumbar punctures (LPs) for administration of intrathecal chemotherapy. With myelosuppressive chemotherapy, thrombocytopenia is common and patients often require platelet transfusions in order to reduce the risk of bleeding during invasive procedures. However, there is a dearth of evidence supporting a platelet threshold required for LPs. Guidelines from the American Association of Blood Banks recommend a minimum platelet count of 50 x 103/µL, but this is based largely on expert opinion. Platelet transfusion is associated with risk of transfusion reaction and alloimmunization, cost, and procedural delays. Given these risks, we instituted a reduction in platelet threshold to 40 x 103/µL for lumbar puncture. We retrospectively reviewed patient outcomes to assess the safety and efficacy of this approach. Methods: In November 2017, a platelet count threshold for LPs was introduced for adult oncology patients in both the inpatient and outpatient settings at Froedtert and the Medical College of Wisconsin. Previous guidelines recommended a platelet count of 50 x 103/µL in order to undergo a lumbar puncture. This threshold was decreased to 40 x 103/µL for oncology patients. Guidelines were agreed upon and implemented in all procedure settings: the inpatient procedure team, the outpatient procedure suite, and the radiology department (for fluoroscopy-guided lumbar puncture). Data regarding the pre-procedure platelet count, number of platelet transfusions given per procedure, CSF RBCs, and occurrence of post-procedure spinal hematomas were collected through the electronic medical record. Results: From November 1, 2016 to May 1, 2018 267 oncology patients underwent a lumbar puncture. Oncologic diagnosis was NHL, ALL, AML, solid malignancy, or other hematologic malignancy/disorder in 26%, 23%, 18%, 16%, and 17%, respectively. 42% of were female. A total of 845 LPs were performed under fluoroscopy, with ultrasound guidance, and by an experienced provider in 26%, 58%, and 16% of cases respectively. 534 LPs (63%) were performed with a platelet transfusion threshold of 50 x 103/µL (Plt≥50) and 311 LPs (37%) were performed with a platelet transfusion threshold of 40 x 103/µL (Plt≥40). The average pre-LP platelet count was 152.8 x 103/µL in the Plt≥50 group and 138.4 x 103/µL in the Plt≥40 group. 79 patients in the Plt≥50 group and 42 patients in the Plt≥40 group had a recorded platelet count between 40-49 x 103/µL within 24 hours prior to the procedure. After institution of the new guidelines, 40 LPs were performed with a platelet count < 50 x 103/µL. The average number of units of platelets transfused per procedure significantly decreased from 0.58 to 0.39 after lowering the transfusion threshold (p < 0.05). One lumbar epidural hematoma occurred post-intervention and one lumbar subarachnoid hematoma occurred pre-intervention, both in patients whose pre-procedure platelet counts were > 100 x 103/µL. No traumatic hematomas were observed in patients whose pre-procedure platelet count was < 50 x 103/µL. The incidence of traumatic taps (identified as CSF red blood cells > 10/µL) was significantly higher in patients whose pre-procedure platelet count was < 50 x 103/µL (64% vs. 46%, p <0.05). Conclusion: Decreasing the LP platelet transfusion threshold from 50 x 103/µL to 40 x 103/µL significantly reduced platelet transfusions. This was not associated with an increased risk of complications. However, the incidence of traumatic taps was significantly higher in patients with a platelet count < 50 x 103/µL. Given that the average cost of one unit of platelets is approximately $500 and 40 procedures were performed with a platelet count < 50 x 103/µL, decreasing the platelet transfusion threshold resulted in a cost savings of approximately $20,000 over the course of 6 months, not including administrative costs. Overall, this data suggests that lowering the platelet transfusion threshold for lumbar punctures to 40 x 103/µL is both safe and cost effective for oncology patients. Disclosures Atallah: Abbvie: Consultancy; Jazz: Consultancy; Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy.

scholarly journals Severity of Thrombocytopenia at the Time of Platelet Transfusion Influences Post-Transfusion Platelet Kinetics and the Effects of Platelets on Plasma Cytokines in a Model of Murine Neonatal Sepsis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 98-98
Author(s):  
Patricia Davenport ◽  
Jorge Canas ◽  
Viola Lorenz ◽  
Zhi-Jian Liu ◽  
Chiara Badur ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Platelet Transfusion ◽  
Bleeding Risk ◽  
Tnf Alpha ◽  
Preterm Neonates ◽  
Laboratory Equipment ◽  
Newborn Mice ◽  
Plasma Cytokines ◽  
Anti Inflammatory ◽  
Platelet Transfusions

Thrombocytopenia affects 20-30% of neonates admitted to the Neonatal Intensive Care Unit (NICU) and up to 70% of those born extremely prematurely, with sepsis being one of the most frequent causes. Since preterm neonates also have a high bleeding risk, it has been widely accepted that they should receive platelet transfusions at higher platelet count (PC) thresholds than older children or adults. However, there is no consensus regarding what the appropriate threshold should be, particularly in critically ill infants. Surveys and observational studies have revealed extraordinary world-wide variability in neonatal platelet transfusion thresholds, with North-American neonatologists typically using more liberal thresholds (i.e. PC&lt;100x109/L) than European neonatologists. Here we hypothesized that the severity of thrombocytopenia at the time of platelet transfusion would influence the post-transfusion platelet kinetics and the effects of platelets on the inflammatory response of septic newborn mice. To test these hypotheses, we used a validated model of neonatal sepsis/peritonitis, consisting of injecting cecal slurry (CS) or 15% glycerol (control) IP into post-natal day 10 (P10) mice. The CS dose used in these studies induced severe sepsis with a high mortality. c-MPL KO pups (which lack the TPO receptor, pre-infection PC 92±38 x 103/µL) and WT B6 pups (pre-infection PC 748±169 x 103/µL) were used to model severe and mild thrombocytopenia at the time of transfusion, respectively. Two hours after infection, mice from both genotypes were transfused with washed platelets from adult GFP mice (5x107platelets/gram) or with Tyrode's buffer. PCs and GFP% were measured by flow cytometry 2 and 22 hrs post-transfusion. At 2 hours, as expected, transfused septic mice of both genotypes had higher PCs than non-transfused septic littermates (217±118 vs 24±9 x103/µL for c-MPLKO mice, p&lt;0.0001, and 764±193 vs. 549±155 x103/µL for WT mice, p&lt;0.01). By 22 hours post-transfusion, transfused septic c-MPL KO mice still had significantly higher PCs than their non-transfused septic littermates (127±71 vs. 21±12 x103/µL, p&lt;0.01; n=7 per group), but there were no significant differences between transfused and non-transfused septic WT mice (415±139 vs. 310±113 x 103/µL, p=0.1;n=7 per group). Between 2 and 22 hrs post-transfusion, PCs dropped at a nearly three-fold higher rate in transfused septic WT mice than in transfused septic c-MPL KO mice (by 17±8 vs. 6±5 x103 platelets/µL/h). In that interval, adult transfused platelets (GFP+) decreased by a larger percentage than neonatal platelets (GFP-) in transfused septic mice of both genotypes (by 64±14% vs. 46±21% in WT mice, and by 53±27% vs. 28±28% in c-MPL KO mice, both p&lt;0.01), although these observations don't account for ongoing neonatal platelet production. Examination of a panel of plasma cytokines 24h after infection revealed significantly increased levels of pro-inflammatory (IL-6, TNF-alpha, and MCP-1) and anti-inflammatory (IL-10) cytokines in non-transfused septic neonates of both genotypes, compared to controls. Interestingly, platelet transfusions significantly reduced the levels of these cytokines in septic WT mice compared to non-transfused littermates, but had no effect on the cytokine levels of septic c-MPLKO mice. Platelets have been recently shown to reduce TNF-alpha production by murine macrophages at high LPS concentrations (Xiang, 2013) and to sequester both pro- and anti-inflammatory cytokines released by monocytes in response to LPS (Carestia, 2019). Our findings suggest that, in neonatal sepsis, this might require PCs to be above a certain threshold. The consequences of these differences on the outcomes of neonatal sepsis are being investigated. Disclosures Stowell: Grifols: Honoraria. Sola-Visner:Sysmex America, Inc.: Other: Laboratory equipment on loan, Research Funding.

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