Platelet Transfusion Strategy Research Articles

Impact of restrictive platelet transfusion strategies on transfusion rates: A cohort study in very preterm infants.

Evidence supports a restrictive platelet transfusion threshold in preterm neonates. We aimed to describe the effect of implementing this threshold on transfusion rates. This retrospective observational cohort study included all very preterm infants (born <32 weeks' gestation) admitted to a neonatal intensive care unit between 2004 and 2022, divided into three epochs. Platelet transfusion thresholds changed from 30 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2004 to December 2009) to 20 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2010 to June 2019) to 25 × 109/L for non-bleeding neonates and 50 × 109/L for neonates with major bleeding (July 2019 to July 2022). The primary outcome was the percentage of transfused neonates in each epoch. Secondary outcomes included the median number of transfusions per neonate, the percentage of transfusions given above 25 or 50 × 109/L, and major bleeding and mortality rates. The percentage of neonates transfused was 12.2% (115/939), 5.8% (96/1660), and 4.8% (25/525) in Epoch I, II, and III, respectively (p < .001), a relative reduction of 61%. The median number of transfusions per transfused neonate was 2.0 (interquartile range [IQR]: 1.0-3.0) in Epoch I, and 1.0 (IQR: 1.0-2.0) in subsequent Epochs (p = .04). The percentage of infants receiving at least one transfusion above 50 × 109/L in Epoch I, II, and III was 51.3% (59/115), 17.7% (17/96), and 20.0% (5/25; p < .001). Mortality and bleeding rates did not significantly differ between epochs. Implementation of restrictive platelet guidelines led to reduction of the rate and number of platelet transfusions.

Clinical outcomes in critically ill children on extracorporeal membrane oxygenation with severe thrombocytopenia

Introduction As international guidelines suggest keeping the platelet count between 50 and 100 × 109 cells/L in children on extracorporeal membrane oxygenation (ECMO), platelet transfusions are administered to two-thirds of ECMO days, and up to 70% of these patients still bleed. We aim to describe outcomes in critically ill children who develop severe thrombocytopenia on ECMO. Methods Single-center retrospective study, enrolling critically ill children on ECMO admitted at Children’s Memorial Hermann, TX, between 1/2018 and 12/2022, with at least one platelet count below 50 × 109 cells/L (severe thrombocytopenia). Platelet counts were measured four times a day. We report platelet transfusion, bleeding, hemolysis, and clotting events within 6 h after transfusion, as well as ECMO duration and mortality. Results We enrolled 54 patients representing 337 ECMO days and 1190 platelet counts. Median weight was 3.7 kg and 54% were male. Severe thrombocytopenia was observed in 56% of platelet counts. Severe thrombocytopenia was not associated with bleeding in the subsequent 6 h (18% vs 20%, p = .95), but was associated with more frequent platelet transfusions (18% vs 11%, p = .001). There was no correlation between time spent with severe thrombocytopenia and the duration of ECMO (R2 = 0.03). While the time spent with severe thrombocytopenia was not associated with on-ECMO mortality rate ( p = .36), there was an association with in-hospital mortality rate ( p = .003). Conclusions Our results indicate a restrictive platelet transfusion strategy is not associated with higher proportions of subsequent bleeding, duration of ECMO, or on-ECMO mortality rate. Multicenter studies are needed to evaluate further the appropriateness of this strategy.

Rare bleeding disorders: Advances in management

Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.

Anticoagulation and hemostasis on extracorporeal membrane oxygenation.

The purpose of this review is to describe the hemostatic changes induced by extracorporeal membrane oxygenation (ECMO), the need to balance the risks of bleeding and clotting with anticoagulation and hemostatic transfusions, and the inherent risks to these interventions. Both bleeding and clotting are frequent complications of ECMO. To prevent clotting events, virtually, all children are anticoagulated. However, the optimal anticoagulation strategy is unknown. A recent systematic review of observational studies showed that anti-Xa-guided strategies were associated with a two-fold decrease in bleeding and no increase in clotting complications. These results need to be tested in randomized controlled trials. To avoid bleeding events, platelet transfusions are frequently prescribed to children on ECMO. However, platelet transfusions have recently been shown to be independently associated with increased bleeding and clotting. Therefore, the optimal platelet transfusion strategy must be evaluated appropriately. Most patients on ECMO will develop either a hemorrhagic or thrombotic complication. Balancing these risks involves careful titration of anticoagulation to prevent clotting and hemostatic transfusions to prevent bleeding. As the current level of evidence is low, prospective randomized trials are needed.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Noncardiac Surgery and Critically Ill Children Undergoing Invasive Procedures Outside the Operating Room: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding. Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. Not applicable. Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery. None. A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room. Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations.

Plasma and Platelet Transfusion Strategies in Critically Ill Children With Malignancy, Acute Liver Failure and/or Liver Transplantation, or Sepsis: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

To present the consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. Not applicable. Critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation. None. A panel of 13 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 12 expert consensus statements. In the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program, the current absence of evidence for use of plasma and/or platelet transfusion in critically ill children with malignancy, acute liver disease and/or following liver transplantation, and sepsis means that only expert consensus statements are possible for these areas of practice.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. Not applicable. Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. None. A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements. The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.

Research Priorities for Plasma and Platelet Transfusion Strategies in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

To present a list of high-priority research initiatives for the study of plasma and platelet transfusions in critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. Not applicable. Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions. None. A panel of 13 experts developed research priorities for the study of plasma and platelet transfusions in critically ill children which were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. The specific priorities focused on the following subpopulations: severe trauma, traumatic brain injury, intracranial hemorrhage, cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, oncologic diagnosis or stem cell transplantation, acute liver failure and/or liver transplantation, noncardiac surgery, invasive procedures outside of the operating room, and sepsis and/or disseminated intravascular coagulation. In addition, tests to guide plasma and platelet transfusion, as well as component selection and processing, were addressed. We developed four general overarching themes and 14 specific research priorities using modified Research and Development/University of California, Los Angeles methodology. Studies are needed to focus on the efficacy/harm, dosing, timing, and outcomes of critically ill children who receive plasma and/or platelet transfusions. The completion of these studies will facilitate the development of evidence-based recommendations.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation (Russian Translation of Cochrane Plain Language Summary)

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Crighton GL, Estcourt LJ, Wood EM, Trivella M, Doree C, Stanworth SJ. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews 2015, Issue 9. Art. No.: CD010981. DOI: 10.1002/14651858.CD010981.pub2

Use of an Antifibrinolytic Agent and Vitamin K As Alternative to Platelet Transfusions in Autologous Hematopoietic Cell Transplantation

BackgroundManaging thrombocytopenia with a prophylactic strategy was previously recommended for patients with impaired bone marrow function, hematological malignancies, and recipients of HCT when platelet counts declined to under 10,000/uL. However, the updated 2018 ASCO guidelines now suggest a place for a therapeutic i.e., after a bleeding event rather than a prophylactic platelet transfusion strategy for patients with hematologic malignancies undergoing autologous HCT. Studies show a lack of significant difference between trial groups in hemostatic outcomes, such as the number of WHO grade 2-4 bleeds, and number of days with bleeding events. Platelet transfusions increase risks of infectious and non-infectious complications as well as inducing a platelet refractory state. Our Transfusion Free Medicine Program has now performed over 200 autologous hematopoietic stem cell transplants (HCT) in Jehovah's Witnesses who due to religious convictions, do not accept red cell or platelet transfusions.Vitamin K is a fat-soluble vitamin that is required for normal blood clotting. Autologous HCT patients are at risk for vitamin K deficiency from multiple reasons including malnutrition, frequent use of antibiotics, chemotherapy induced gastrointestinal toxicity leading to malabsorption and colitis. The prothrombin test lacks the sensitivity and specificity to detect mild deficiency. A mild vitamin K deficiency may be underdiagnosed in our transplant patients adding to bleeding risk. With the effective use of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions we believe this may enhance hemostasis and prove a valuable adjunct to a therapeutic approach.MethodsPatients in our study were those who were of the Jehovah's Witness faith undergoing autologous HCT for Multiple Myeloma and Lymphoma. Patients received aminocaproic acid as an alternative to platelet transfusion to enhance hemostasis at a dose of 1 g every 4 hours or prophylactically for platelet counts less than 30,000 /uL. Titration to 4 g every 4 hours intravenously was required for platelet counts less than 10,000/ul or clinical bleeding. Vitamin K 10 mg orally or subcutaneous was also started at this time.ResultsTable 1 illustrates the low number of bleeding events especially grade 3 or 4 that occurred. There were no Grade 3 or 4 bleeding events in patients with platelet counts above 5000/uL. No patient had residual long term effects nor was there an increase in thromboembolic events.ConclusionsThese data add to the body of literature supporting a therapeutic platelet transfusion strategy in an experienced center for autologous HCT patients and challenges the prophylactic platelet count of 10,000 /uL suggesting instead 5000/uL. The safety and efficacy of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions to enhance hemostasis in autologous stem cell transplant patients may prove beneficial not only in JW patients but also in those transplant centers wishing to offer a therapeutic platelet transfusion approach and as a strategy to manage platelet refractoriness. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Aminocaproic Acid is an antifibrinolytic agent approved for treatment of bleeding in surgical patients and hematological bleeding disorders. Vitamin K is approved for use in reversal of anticoagulation from Warfarin, vitamin K deficiency without liver disease and in the newborn.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation (Russian Translation of Cochrane Plain Language Summary – PLS)

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Crighton GL, Estcourt LJ, Wood EM, Trivella M, Doree C, Stanworth SJ. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews 2015, Issue 9. Art. No.: CD010981. DOI: 10.1002/14651858.CD010981.pub2

Особенности вязко-эластических свойств сгустка крови и проявления геморрагического синдрома при тромбоцитопении у онкогематологических больных

Введение. Тромбоцитопения является частым осложнением онкогематологических заболеваний, которое провоцирует развитие геморрагического синдрома. Уровень тромбоцитов в периферической крови, являющийся пороговым для переливания концентрата тромбоцитов (КТ), окончательно не установлен. Применение тромбоэластографии (ТЭГ) при тромбоцитопениях у онкогематологических больных может повысить прогностические возможности определения риска кровотечений. Цель исследования: оценить вязко-эластические свой ства сгустка крови при тромбоцитопении менее 50×109/л и их взаимосвязь с проявлениями геморрагического синдрома у онкогематологических больных. Материалы и методы. В исследование включено 84 пациента с гемобластозами и тромбоцитопенией менее 50×109/л, 54 (64%) мужчины и 30 (36%) женщин, медиана возраста — 54 года. В зависимости от уровня тромбоцитов в периферической крови пациентов разделили на 2 группы: группа 1 — 44 пациента с числом тромбоцитов от 25 до 50×109/л, группа 2 — 40 больных с содержанием тромбоцитов менее 25×109/л. Исследовали показатели периферической крови, коагулограммы и ТЭГ. Степень тяжести кровотечений оценивали по шкале проявлений геморрагического синдрома (ВОЗ) и по шкале оценки побочных явлений Национального института рака (США). Результаты. Гипокоагуляция по ТЭГ в группе 1 выявлена в 46% случаев, в группе 2 — в 75%. Значимые межгрупповые различия показателей ТЭГ получены только в отношении максимальной амплитуды. Геморрагический синдром в группе 1 диагностирован у 6 (13%) пациентов, в группе 2 — у 14 (35%). Однако предиктивная роль влияния количества тромбоцитов на частоту развития геморрагического синдрома не установлена (β = 0,016; p = 0,92). Сочетание тромбоцитопении и гипокоагуляции по ТЭГ проявлялось в виде геморрагического синдрома в 3,3 раза чаще, чем без гипокоагуляции (RR = 3,3; 95% ДИ = 1,20–9,05). В ряде случаев основанная на результатах ТЭГ трансфузионная тактика позволила избежать переливания КТ при инвазивных манипуляциях у больных с тромбоцитопенией менее 25 × 109 / л. Заключение. Глубина тромбоцитопении не является надежным предиктором геморрагического синдрома. Применение ТЭГ у пациентов с тромбоцитопенией позволяет оптимизировать трансфузионную тактику, избежав ненужных переливаний КТ. Сочетание тяжелой тромбоцитопении с гипокоагуляцией по данным ТЭГ служит показанием для профилактических трансфузий КТ. Background. Thrombocytopenia is a frequent complication of hemoblastosis that causes hemorrhagic syndrome. The threshold of peripheral blood platelet count for transfusion of platelet concentrate is discussed. Thromboelastography (TEG) can be considered as additional prognostic method for bleeding risk assessment in thrombocytopenic patients with leukemia. Objectives: to study changes in the viscoelastic properties of blood clot in hemoblastosis patients with thrombocytopenia less than 50×109/L and their relationship with the manifestations of hemorrhagic syndrome. Patients/ Methods. The study included 84 hemoblastosis patients — 54 (64%) men и 30 (36%) women with thrombocytopenia less than 50 × 109/L, median age — 54 years. All patients are divided into 2 groups according to the platelet count: Group 1 — 25–50×109/L, Group 2 — less than 25×109/L. Peri pheral blood counts, TEG and coagulogram parameters were evaluated in both groups. Manifestations of hemorrhagic syndrome were assessed according to the WHO bleeding scale and Common terminology criteria for adverse events of the National Cancer Institute (USA). Results. Hypocoagulation according TEG in Group 1 was found in 46% of cases, in Group 2 — in 75%. Significant intergroup differences in TEG parameters were obtained only in maximum amplitude. Hemorrhagic syndrome in Group 1 diagnosed in 6 (14%) patients, in Group 2 — in 14 (35%). There was no dependence of hemorrhagic syndrome frequency on the severity of thrombocytopenia (β = 0.016; p = 0.92). The combination of thrombocytopenia and hypocoagulation according TEG manifested as a hemorrhagic syndrome 3.3 times more often than without hypocoagulation (RR = 3.3; 95% CI = 1.20–9.05). In some cases, TEG-based transfusion tactics allowed to avoid unnecessary platelet concentrate transfusion during invasive procedures in patients with thrombocytopenia less than 25 × 109/L. Conclusions. Severity of platelet depletion is not accuracy predictor for hemorrhagic events. Use of TEG in patients with thrombocytopenia allows to optimize the transfusion tactics and to avoid unnecessary platelet concentrate transfusions. The combination of severe thrombocytopenia with hypocoagulation according TEG serves as indication for prophylactic platelet concentrate transfusion.

Dysregulated pathways and differentially expressed proteins associated with adverse transfusion reactions in different types of platelet components

Platelet components (PCs) are occasionally associated with adverse transfusion reactions (ATRs). ATRs can occur regardless of the type of PC being transfused, whether it is a single-donor apheresis PC (SDA-PC) or a pooled PC (PPCs). The purpose of this study was to investigate the proteins and dysregulated pathways in both of the main types of PCs.The proteomic profiles of platelet pellets from SDA-PCs and PPCs involved in ATRs were analysed using the label-free LC-MS/MS method. Differentially expressed proteins with fold changes >|1.5| in clinical cases versus controls were characterised using bioinformatic tools (RStudio, GeneCodis3, and Ingenuity Pathways Analysis (IPA). The proteins were confirmed by western blotting.The common primary proteins found to be dysregulated in both types of PCs were the mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), multimerin-1 (MMRN1), and calumenin (CALU), which are associated with the important enrichment of platelet activation, platelet degranulation, and mitochondrial activity. Furthermore, this analysis revealed the involvement of commonly dysregulated canonical pathways, particularly mitochondrial dysfunction, platelet activation, and acute phase response. This proteomic analysis provided an interesting contribution to our understanding of the meticulous physiopathology of PCs associated with ATR. A larger investigation would assist in delineating the most relevant proteins to target within preventive transfusion safety strategies. Biological significanceWithin platelet transfusion strategies, the two primary types of PCs predominantly processed in Europe, include (i) single donor apheresis PCs (SDA-PCs) from one donor and (ii) pooled PCs (PPCs). The current study used PCs from five buffy coats derived from five whole blood donations that were identical in ABO, RH1 and KEL1 groups. Both PC types were shown to be associated with the onset of an ATR in the transfused patient.Several common platelet proteins were found to be dysregulated in bags associated with ATR occurrences regardless of the type of PCs transfused and of their process. The dysregulated proteins included mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), which is involved in a fatty acid oxidation disorder; calumenin (CALU); and multimerin-1 (MMRN1), which is chiefly involved in platelet activation and degranulation. Dysregulated platelet protein pathways for ATRs that occurred with SDA-PCs and PPCs could support the dysregulated functions found in association with those three proteins. Those common platelet proteins may become candidates to define biomarkers associated with the onset of an ATR from PC transfusions, including monitoring during the quality steps of PC manufacturing, provided that the results are confirmed in larger cohorts. This study enriches our knowledge of platelet proteomics in PCs under pathological conditions.

Platelet Transfusion in Perioperative Medicine.

Platelet 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.

RhTyrRS (Y341A), a novel human tyrosyl-tRNA synthetase mutant, stimulates thrombopoiesis through activation of the VEGF-R II/NF-κB pathway

Bacground and purposeTumor chemotherapy and radiotherapy induces hematopoietic cell damage, resulting in thrombocytopenia. Conventional platelet transfusion strategies or drug therapies are used to treat thrombocytopenia. However, these therapies may result in a several side effects, including heightened susceptibility to infectious diseases and the formation of anti-TPO-antibodies. Therefore, a more secure strategy should be explored to overcome and compensate for the shortcomings of conventional strategies. Experimental approachEffects of rhTyrRS(Y341A) on the expression of VCAM-1 on the surface of HUVECs were determined by analysing mRNA expression, promoter activity, protein expression. The molecular mechanisms of the effects of rhTyrRS(Y341A) on the expression of VCAM-1 on the surface of HUVECs were investigated by determining the activation of VEGF-R II/NF-κB pathway. Key resultsOur results provide evidence that rhTyrRS (Y341A) activates NF-κB to upregulate VCAM-1 in a VEGF-R II/NF-κB pathway-dependent, resulting in megakaryocyte adhering to PVECs to induce platelet production. ConclusionsThis study suggested that rhTyrRS (Y341A), a novel human tyrosyl-tRNA synthetase mutation, increased the platelet count under normal conditions. Further more, we confirmed that an NF-κB-mediated mechanism is involved in rhTyrRS (Y341A)-induced thrombopoiesis, which involves its interaction with VEGF-R II.

Prophylactic Platelet Transfusions for Critically Ill Patients With Thrombocytopenia: A Single-Institution Propensity-Matched Cohort Study.

Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9-9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

Low Incidence of Bleeding Events With a Restrictive Platelet Transfusion Protocol in Patients With Cirrhosis and Concomitant End Stage Renal Disease

Introduction: Management of ascites in cirrhosis with concomitant end-stage renal disease (ESRD) presents a challenge as diuretic titration and transjugular portosystemic shunt (TIPS) effectiveness are limited. Patients are often managed with serial large volume paracentesis (LVPs); both quantitative and qualitative platelet dysfunction may increase LVP bleed risk. Society guidelines differ with respect to minimum platelet thresholds for safe LVP. The primary aim of this study was to characterize rate of bleeding in a population with cirrhosis and ESRD receiving LVP with a restrictive platelet transfusion strategy. Methods: Retrospective study of consecutive inpatients LVP at a tertiary medical center between January 2016 and December 2017. Institutional clinical census developed a protocol in which no patients received fresh frozen plasma (FFP), platelets or desmopressin prior to ultrasound guided LVP. Records tabulated: date/time of LVP, complete blood profile (CBC), INR and model for end stage liver disease (MELD score) on day of procedure, any blood products transfused during inpatient stay, and any angiogram procedures performed. Details of any secondary hospital encounter within 2 weeks of LVP reviewed. Results: 757 inpatients underwent usLVP. Mean INR, platelet count and MELD was 2.1 (1.7-2.8), 124 (11-157k) and 24 (21-36) respectively. 35% of patients had INRs > 2.0. 131 patients (17%) had platelet counts < 50k and 32 patients (4%) had < 30k. 260 patients (34%) were on renal replacement therapy RRT) at the time of usLVP. An additional 52 patients had Cr >2.0 (7%). Only 1 of 757 patients (0.13%) had post-LVP bleeding requiring transfusion of 2 units of packed red blood cells. No patient required angiogram intervention for bleeding and no patient died from LVP related complications. Conclusion: Incidence of bleeding with ultrasound guided LVP is very rare, even in a high risk patient population with severe renal dysfunction and thrombocytopenia. Prophylactic product transfusion or desmopressin do not appear warranted in this high risk population.

Abstract PCCLB-69: TRANSFUSION RELATED ACUTE HEPATIC INJURY (TRAHI) IN PEDIATRIC PATIENTS UNDERGOING THE FONTAN PROCEDURE

Aims & Objectives: The final common pathway of single ventricle patients is the Fontan procedure. One of the immediate postoperative complications is acute hepatic injury presented by marked elevation of liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)). Aims: We aimed to determine the contribution of blood products transfusion to acute hepatic injury. Methods We retrospectively reviewed demographic, pre-, intra- and post-operative parameters including blood products transfusions and liver enzymes (Table 1). ALT and AST levels were transformed into log scale for the regression analysis. We used the Spearman correlation while adjusting for possible confounders. Propensity score was used in order to perform a stepwise weighted linear regression. Results 99 pediatric patients after the Fontan procedure were identified between 01/2009 and 12/2016. Out of the four types of blood products, transfusion of platelets was found to significantly impact post-operative levels of ALT and AST (Figure 1). Additional factors include post-operative administration of sodium bicarbonate, decreased flow through the Fontan canal and decreased urine output. Cardiopulmonary bypass time, aortic cross-clamp time, amount of post-operative bleeding and vasoactive-inotropic score did not influence liver enzymes levels (Table 2). Conclusions In pediatric patients undergoing the Fontan procedure, platelets transfusions significantly contribute to acute hepatic injury. The relation between platelets and transfusion related acute lung injury (TRALI) has been well described, but this is the first time it is being described in regards to acute hepatic injury (TRAHI). Changing platelet transfusion strategy could decrease morbidity in Fontan patients but further research is needed.

Intracranial hemorrhage in adults on ECMO.

Extracorporeal membrane oxygenation (ECMO) use has exploded over the last decade. However, it remains invasive and associated with significant complications, including tamponade, infection, thrombosis, gas embolism and bleeding. The most dreaded complication is intracranial hemorrhage (ICH). In this article, we review the literature on the incidence, diagnosis, risk factors, pathophysiology, prognosis, prevention and management of ICH in adults on ECMO. We found a high incidence of ICH in the literature with a poor prognosis. Important risk factors included pre-ECMO cardiac arrest, sepsis, influenza, renal failure, renal replacement therapy, hemolysis and thrombocytopenia. The optimal anticoagulation strategy is still uncertain. As platelet dysfunction and depletion appear to play an important role in the pathogenesis of ICH in patients on ECMO, a liberal platelet transfusion strategy may be advised. Prompt computed tomography (CT) diagnosis is of great importance as interventions to limit hematoma expansion and secondary neurological injury are most effective if instituted early. Transporting patients to the radiology department can be performed safely while on ECMO. A strategy combining screening CT on admission with a heparin-free period of extracorporeal support was demonstrated to be safe in VV-ECMO patients and resulted in a better prognosis compared to similar cohorts in the literature. Despite major technological improvements and all the experience gained in adults, ECMO remains associated with a high incidence of ICH. There are still wide gaps in our understanding of the disease. Optimal management strategies that minimize the risk of ICH and improve prognosis need to be further studied.

Thrombocytopenia and bleeding in myelosuppressed transfusion-dependent patients: a simulation study exploring underlying mechanisms.

BackgroundHematology–oncology patients often become severely thrombocytopenic and receive prophylactic platelet transfusions when their platelet count drops below 10×109 platelets/L. This so-called “platelet count trigger” of 10×109 platelets/L is recommended because currently available evidence suggests this is the critical concentration at which bleeding risk starts to increase. Yet, exposure time and lag time may have biased the results of studies on the association between platelet counts and bleeding risks.MethodsWe performed simulation studies to examine possible effects of exposure time and lag time on the findings of both randomized trials and observational data.ResultsExposure time and lag time reduced or even reversed the association between the risk of clinically relevant bleeding and platelet counts. The frequency of platelet count measurements influenced the observed bleeding risk at a given platelet count trigger. A transfusion trigger of 10×109 platelets/L resulted in a severely distorted association, which closely resembled the association reported in the literature. At triggers of 0, 5, 10, and 20×109 platelets/L the observed percentages of patients experiencing bleeding were 18, 19, 19, and 18%. A trigger of 30×109 platelets/L showed an observed bleeding risk of 16% and triggers of 40 and 50×109 platelets/L both resulted in observed bleeding risks of 13%.ConclusionThe results from our simulation study show how minimal exposure times and lag times may have influenced the results from previous studies on platelet counts, transfusion strategies, and bleeding risk and caution against the generally recommended universal trigger of 10×109 platelets/L.