Therapeutic Platelet Transfusions Research Articles

Platelet Transfusion in Clinical Practice: A Narrative Literature Review

Platelet transfusion plays a vital role in clinical practice, serving as a cornerstone in the management of various medical conditions. Thrombocytopenia, characterized by a low platelet count, can result from decreased platelet production, increased peripheral platelet destruction, increased splenic sequestration, or dilutional thrombocytopenia. Platelet transfusion is commonly administered for prophylactic purposes to prevent bleeding in patients with hypoproliferative thrombocytopenia and before invasive procedures or surgeries. In cases of bleeding or significant bleeding risk, therapeutic platelet transfusion is employed. This review article aims to provide an understanding of platelet transfusion and its applications in daily clinical practice. The dosage and administration of platelet transfusion, as well as potential complications, are discussed. Understanding the indications, contraindications, and appropriate use of platelet transfusion is crucial for optimizing patient outcomes and ensuring safe and effective clinical practice.

Coagulopathy of Dengue and COVID-19: Clinical Considerations.

Thrombocytopenia and platelet dysfunction commonly occur in both dengue and COVID-19 and are related to clinical outcomes. Coagulation and fibrinolytic pathways are activated during an acute dengue infection, and endothelial dysfunction is observed in severe dengue. On the other hand, COVID-19 is characterised by a high prevalence of thrombotic complications, where bleeding is rare and occurs only in advanced stages of critical illness; here thrombin is the central mediator that activates endothelial cells, and elicits a pro-inflammatory reaction followed by platelet aggregation. Serological cross-reactivity may occur between COVID-19 and dengue infection. An important management aspect of COVID-19-induced immunothrombosis associated with thrombocytopenia is anticoagulation with or without aspirin. In contrast, the use of aspirin, nonsteroidal anti-inflammatory drugs and anticoagulants is contraindicated in dengue. Mild to moderate dengue infections are treated with supportive therapy and paracetamol for fever. Severe infection such as dengue haemorrhagic fever and dengue shock syndrome often require escalation to higher levels of support in a critical care facility. The role of therapeutic platelet transfusion is equivocal and should not be routinely used in patients with dengue with thrombocytopaenia and mild bleeding. The use of prophylactic platelet transfusion in dengue fever has strained financial and healthcare systems in endemic areas, together with risks of transfusion-transmitted infections in low- and middle-income countries. There is a clear research gap in the management of dengue with significant bleeding.

Blood Transfusion Practices in Dengue Fever: A Cross Sectional Single Center Study During a Dengue Outbreak in Pakistan

Introduction: Dengue fever (DF) is a global health problem in tropical and subtropical regions across the globe. Pakistan has become one of the countries which are hit by its outbreaks for the past two decades with the first outbreak reported in 1994.It is a mosquito-borne infection which is transmitted to humans from the mosquito bite. Characteristics of dengue fever are thrombocytopenia, coagulopathy and increased capillary permeability. The disease spectrum ranges from mild fever to life threatening hemorrhagic shock syndrome; hemorrhagic manifestations are the most feared complications of the disease. Guidelines regarding fluid management in dengue fever have been established by Center for Disease Control (CDC) and local national bodies in Pakistan however comprehensive data regarding blood product usage is lacking. Understanding the rationale use of blood products can reduce burden on blood bank inventories as well as reduce unnecessary blood product exposure to the patients in dengue outbreak.
 Aims & Objectives: Assessment of compliance of physicians and transfusion provision authorities regarding blood products usage with local and international guidelines in managing dengue outbreak.
 Place and duration of study: This study was conducted at Chughtai Institute of Pathology, Lahore from September 2021 to November 2021.
 Material & Methods: It was a cross sectional study. Total 107 patients who were non-structural antigen1(NS1) positive confirmed dengue infection presented at Chughtai Blood Bank for request of any blood product were included in the study; individuals with existing cytopenia (known cases) unrelated to Dengue (NS1 antigen positive) were excluded. Data was recorded on a pre-designed Performa/questionnaire. Statistical analysis was performed using SPSS 23.0. Frequencies were calculated and expressed as percentages.
 Results: Mean Age of 107 patients was 53 years (±19.05) out of which 63(58.9%) were males and 44(41.1%) were females. Blood products requested were platelets in 93(86.9%) patients, platelets and fresh frozen plasma in 3(2.8%), platelets and whole blood in 9(8.4%) and whole blood in 2(1.9%) patients. Therapeutic platelet transfusions were done in 35(32.7%) patients and prophylactic platelet transfusions were done in 72(67.3%) patients.
 Conclusion: Lack of practicing evidence-based guidelines and inappropriate usage of blood products during dengue epidemic overburdens health care facilities and adds to the stress and panic. A well-coordinated centralized management system for dengue outbreak can play pivotal role in guiding rationale use of blood products.

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.

Rates of Severe Bleeding Are Low in Patients with MDS and Severe Thrombocytopenia and May be Mitigated By Tranexamic Acid

▪Introduction:While thrombocytopenia is common and affects 29% of patients (pts) with MDS, severe thrombocytopenia (platelets (plt) <20x109/L) affects approximately 10% of pts and is associated with bleeding and higher risk IPSS-R scores.Prophylactic and therapeutic plt transfusions are commonly administered to prevent bleeding in pts with MDS and severe thrombocytopenia but are inconvenient and associated with risks. Since the inception of the MDS registry in 2006 at our centre, we commonly administer tranexamic acid (TXA, 1-1.5 grams PO BID-TID) to thrombocytopenic pts with MDS to decrease minor mucosal bleeding and the use of plt transfusions for non-severe bleeds. The administration of prophylactic and/or therapeutic plt transfusions is at the discretion of the treating haematologist.Objective:To retrospectively audit the bleeding rates and transfusion requirements of pts with MDS and durable severe thrombocytopenia as related to TXA use, plt transfusions, and disease characteristics.Methods:All pts with MDS with durable severe thrombocytopenia (plt count <20x109/L in ≥50% of days over an 8-week period) treated at Sunnybrook Health Sciences Centre and registered in the prospective MDS registry were eligible. Bleeding events, rated with the World Health Organization bleeding scale were captured by registry and chart review. The highest grade bleed experienced by the patient was assigned once for each clinic visit documenting a bleeding event. Platelet transfusion frequency and quantity during the period of severe thrombocytopenia were obtained. Platelet transfusions were considered prophylactic (PROPH) if they occurred at a recurring time interval of ≤2 weeks, and were considered therapeutic otherwise. Descriptive statistics are reported, and ANOVA or correlation coefficients were calculated where relevant.Results:Of 200 pts with severe thrombocytopenia at any time, 99 had durable severe thrombocytopenia and were included. Demographics are presented in Table 1. The pts were classified as receiving TXA alone (n=28), TXA + PROPH, (n=39), PROPH plts alone (n=19) and untreated (n=13). Median time from diagnosis to start of durable severe thrombocytopenia was 0.9 years (IQR 0.2-2.2), duration was 27 weeks (IQR 16-49), and median plt count was 12x109/L (IQR 9-16). Pts receiving TXA +/- PROPH plts had significantly higher rates of concurrent red blood cell transfusion dependence. With a median follow-up of 0.8 years (95% CI 0.6-1.2), actuarial survival was 0.9 years (95% CI 0.7-1.2).68% of pts were prescribed TXA at any point with a median time from onset of severe thrombocytopenia of 5 weeks (IQR 0-13) and a median duration of 23 weeks (IQR 12-41). Only 32% and 23% of TXA alone and untreated pts respectively required therapeutic plt transfusions at any point with a median time between transfusions of 2.8 and 4.0 weeks respectively. The median number of plt transfusion events per 4-week period was 0 for TXA alone and untreated pts compared with 2.2 and 3.1 events for TXA + PROPH or PROPH alone (p<0.0001) (Table 2).During the period of severe thrombocytopenia, 82% (81/99) of pts had at least one bleeding event, and 5% (5/99) had a grade 4 bleeding event. There was a significant difference in grade 1 and 2 bleeding rates between groups, with the highest rates in pts on TXA +/- PROPH plts (Table 2). There was no significant difference in grade 3 or 4 bleeding rates between groups.Conclusions:Patients with MDS and durable severe thrombocytopenia at a Canadian tertiary care centre had low rates of major bleeding (5%) compared to what has been previously reported in the literature, but poor overall survival. Seventy-one percent of severely thrombocytopenic pts on TXA or no therapy required no therapeutic platelet transfusions for the duration of study follow-up. The benefit of TXA and/or prophylactic platelet transfusions for the prevention of bleeding would be best evaluated in the context of a randomized controlled trial. [Display omitted] DisclosuresWells:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lin:Pfizer: Honoraria; Pfizer: Other: advisory board; CSL Behring, Grifols: Other: unrestricted education grant; Novartis: Research Funding. Buckstein:Celgene: Honoraria, Research Funding; Astex: Honoraria.

Platelet Transfusion-Insights from Current Practice to Future Development.

Since the late sixties, therapeutic or prophylactic platelet transfusion has been used to relieve hemorrhagic complications of patients with, e.g., thrombocytopenia, platelet dysfunction, and injuries, and is an essential part of the supportive care in high dose chemotherapy. Current and upcoming advances will significantly affect present standards. We focus on specific issues, including the comparison of buffy-coat (BPC) and apheresis platelet concentrates (APC); plasma additive solutions (PAS); further measures for improvement of platelet storage quality; pathogen inactivation; and cold storage of platelets. The objective of this article is to give insights from current practice to future development on platelet transfusion, focusing on these selected issues, which have a potentially major impact on forthcoming guidelines.

Platelet Count Increment after Transfusion of Fresh and Stored Platelet Concentrates in Children with Acute Lymphoblastic Leukaemia

Background: Therapeutic platelet transfusion is necessary to prevent bleeding due to thrombocytopenia in childhood acute lymphoblastic leukaemia (ALL). Platelet concentrates may be transfused as fresh platelet concentrate immediately or with five days of storage after collection Objectives: To compare the platelet count increment between fresh and stored platelet concentrate transfusion in children with acute lymphoblastic leukaemia. Methodology: This observational study was carried out in the Department of Clinical Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, in collaboration with the Department of Transfusion Medicine and Paediatric Haemato-Oncology, BSMMU, Dhaka. Seventy-two children diagnosed as acute lymphoblastic leukaemia were included in this study. ABO identical whole-blood derived platelet-rich-plasma platelet concentrates (PRP-PCs) were transfused within 24 hours of preparation or 1-5 days of storage. Effectiveness of platelet transfusion was carried out by measuring platelet count prior to transfusion, subsequently 1 hour and 24 hours of transfusion. Result: Post transfusion platelet count at 1 hour and 24 hours with fresh platelet concentrates (FPC) and stored platelet concentrates (SPC) were not statistically significant. Post transfusion platelet increment at 1 hour and 24 hours were also similar in both FPC and SPC. Corrected count increment (CCI) at 1 hour in FPC and SPC were 20.5±10.1 and 18.6 ±6.5 respectively and was statistically not significant (P: 0.168). CCI at 24 hours were 15.5±9.1 and 13±5.8 which were also statistically not significant. Percentage platelet recovery at 1 hour and 24 hours in both FPC and SPC were statistically not significant. But these values in SPC were consistently lower than that of FPC. All the values of FPC and SPC were well apart from the lower limit of CCI and percentage platelet recovery (PPR). It was also observed that 85.1% satisfactory platelet transfusion was achieved with FPC and rest of 14.9% was platelet refractory cases. In 79.5% cases satisfactory platelet transfusion were achieved with SPC and refractory cases were 20.5 %. Conclusion: One to five day’s stored PRP-PCs are as effective as fresh PRP-PCs to achieve satisfactory platelet increment.

Bleeding risk in thrombocytopenic patients after dental extractions: a retrospective single-center study.

The aim of the present study was to assess the clinical safety profile of dental extractions in patients with thrombocytopenia and explore the effectiveness of platelet transfusion before dental extractions. This is a retrospective cohort study of patients with moderate to severe (≤100,000/μL) thrombocytopenia who underwent dental extractions in the Oral Medicine and Dentistry Clinic at Brigham and Women's Hospital from 2003 to 2019. Patients with a platelet count <30,000/μL received prophylactic preprocedure platelet transfusion. Risk and type of bleeding complication (prolonged postoperative bleeding requiring intervention with topical hemostatic agents and/or therapeutic platelet transfusions) was assessed. Eighty-nine thrombocytopenic patients were identified. Postextraction bleeding complications occurred in 4 patients (4.4%). Surgical extractions and multiple number of extractions were significantly associated with an increased bleeding risk (P < .05), whereas prophylactic platelet transfusion and post-transfusion platelet count were not. Dental extractions in patients with thrombocytopenia may be performed with a positive safety profile by following a comprehensive medical evaluation, thorough treatment planning, adequate surgical management, use of local hemostatic measures, and, importantly, coordination of care with the patient's medical team.

Evaluation of therapeutic and prophylactic platelet transfusion practices in a neonatal intensive care unit

Evaluation of therapeutic and prophylactic platelet transfusion practices in a neonatal intensive care unit

The management and outcomes of patients with myelodysplastic syndrome with persistent severe thrombocytopenia: An observational single centre registry study

BackgroundSevere thrombocytopenia affects 10% of patients with myelodysplastic syndrome (MDS) and is associated with poor outcomes. The role for prophylactic platelet transfusions in the outpatient setting is unknown. Objective/methodsTo audit treatments, bleeding rates, and transfusion requirements of patients with MDS and persistent severe thrombocytopenia (PST) registered in a prospective MDS registry at our center. Results99 (17%) of 586 total registry patients had PST; 28 were treated with tranexamic acid alone (TXA), 39 with TXA and prophylactic platelet transfusions (PROPH), 19 with PROPH alone, and 13 were untreated. Median duration of PST was 27 weeks and median overall survival was 0.9 years (95% CI 0.7–1.2). During the PST, 6% (6/99) of patients had a grade 4 bleeding event, from which 4 died. Platelet count at the time of grade 4 bleeding ranged from 2 to 19 × 109/L. 66% (27/41) of patients on TXA alone or untreated required no therapeutic platelet transfusions and experienced no grade 3–4 bleeds. There were no significant differences in grade 3–4 bleeding rates between groups. ConclusionsPatients with MDS and PST had low rates of major bleeding but poor overall survival. Disparities in clinical practice likely relate to patient and provider heterogeneity and the lack of published evidence. The benefit of TXA and/or prophylactic platelet transfusions would be best evaluated by a randomized controlled trial.

What is the evidence for platelet transfusion in perioperative settings?

Platelet transfusions are widely administered to restore perioperative haemostasis in haemorrhagic patients; however, the role of platelet transfusion is not well understood and administration is often based on empiric data. This review aims to explore consensus regarding platelet transfusion trigger, dose and how the haemostatic efficacy of platelet transfusion was assessed for the treatment of perioperative bleeding. A literature search was carried out using MEDLINE (PubMed) on 28 February 2017, to identify publications reporting the effect of platelet transfusion in relation to triggers, dose and assessment of haemostatic efficacy in bleeding patients in a perioperative setting. Eight publications were identified across a variety of settings, covering both prophylactic and therapeutic platelet transfusion in adult patients; the majority of the reports were in cardiac surgery. A high degree of variability was observed in the published studies, with only 50% of articles specifying a trigger for platelet transfusion. The most commonly used trigger was platelet count (25% of publications), with no consensus identified regarding the platelet count values used as triggers. Doses reported per transfusion varied from 1 to 12 units, and outcome measures were mixed, although the majority of publications (63%) assessed the requirement for transfusion with other blood products. The lack of consensus in published studies hinders our ability to draw conclusions regarding platelet transfusion and highlights the need for further studies to assess the appropriate dose and triggers for use in perioperative patients.

A Phase I Dose Finding Trial of Eltrombopag during Consolidation Therapy in Adults with Acute Myeloid Leukemia Employing a Unique Dosing Design: PrE0901, a Precog Study

Introduction: High-dose cytarabine consolidation chemotherapy for acute myeloid leukemia (AML) induces profound transient myelosuppression. Thrombocytopenia is a limiting factor in chemotherapy administration for maintaining dose intensity and schedule as thrombocytopenic-related hemorrhage may contribute to significant morbidity and mortality. Therapeutic and prophylactic platelet (plt) transfusions remain the treatment of choice but the benefits typically last only 3-7 days, are expensive, time consuming, and may induce alloimmunization and transmit infection. PrE0901 was a phase I multi-center study to evaluate the safety and toxicity of eltrombopag, an orally bioavailable thrombopoietin (TPO) receptor agonist, for plt recovery in AML patients (pts) receiving consolidation therapy.Methods: The primary objectives were to determine the safety, tolerability, and optimal dosing of eltrombopag while describing the kinetics of plt recovery in AML pts receiving intensive consolidation. Plt recovery was defined as a sustained plt count of ≥ 20 x 109/L following the nadir with no plt transfusions in prior 7 days or a continued upward trend in plt count for at least 2 successive measurements despite no plt transfusions in 48 hours. We used a standard 3+3 design utilizing a novel dose escalation/de-escalation strategy for pts in either first or second complete remission, ≥18 and ≤70 years of age, who had an ECOG performance status of 0-2. Cytarabine was administered at 3 g/m2 (1.5 g/m2 for pts >60 years) IV over 3 hours twice daily on days 1,3,5. Eltrombopag at assigned dose was administered with a first cycle of cytarabine only. Planned eltrombopag dose levels -2, -1, 1, 2, 3, 4, and 5 were 50, 100, 150, 150, 150, 200, and 300 mg, respectively (Table 1). Eltrombopag was to start on days X, X, 3, -1, -5, -5, and -5 relative to day of cytarabine start and levels -2, -1, 1, 2, 3, 4, and 5, respectively, with day X being variable depending on timing of observed dose limiting toxicities (DLTs). The eltrombopag was continued until plt recovery or for up to 35 consecutive days, whichever occurred first. An exploratory objective was to determine if eltrombopag had an effect on TPO and EPO blood concentrations in this setting.Results: Accrual began on July 31, 2012 and the trial closed on January 8, 2016 upon recommendation after an independent Data and Monitoring Committee reviewed a separate trial of eltrombopag therapy in MDS which demonstrated futility. 104 pts were screened. 54 declined participation and 35 were deemed medically ineligible. A total of 15 eligible pts were enrolled; 14 were treated on study with one pt being withdrawn prior to starting treatment due to infection. Three pts were treated at each of dose levels 1-4 and two were treated on dose level 5. No DLTs were observed. Median time to plt recovery of all pts treated on study was 22.5 (range 16-43) days. Pts in cohort 1 dosed with eltrombopag 150 mg daily starting on day 3 of consolidation demonstrated the fastest plt recovery (median =19 days; range 19, 19, 19) compared to cohort 2 who received 150 mg daily starting on day -1 of consolidation and recovered the slowest (median 23 days; range 16, 23, 43). Dose escalation in terms of starting eltrombopag further in advance of chemotherapy exposure as within cohort 3 (150 mg starting day -5) was associated with a median plt recovery of 27 (range 22, 27, 27) days. Eltrombopag dose intensification with cohort 4 at 200 mg daily and cohort 5 at 300 mg daily was associated with median plt recoveries of 24 (range 18, 24, 26) and 23 (range 19, 27) days, respectively. Kinetics of plt recovery for all cohorts are represented in Figure 1 and duration of eltrombopag exposure for each individual patient is represented in Table 2.Conclusions: Endogenous cytokine (TPO and EPO) levels varied inversely with plt and hematocrit values and did not appear to be affected by eltrombopag dose / schedule (details to be provided at ASH Annual Mtg). Unusually high screen fail numbers warrant examination to guide future trial design in the post-remission setting. The addition of eltrombopag to high-dose cytarabine consolidation therapy was well-tolerated and no DLTs were observed. The results for cohort 1 [eltrombopag 150 mg daily starting on day 3 of consolidation] demonstrated the fastest plt recovery. Further investigation is needed to define the optimal role, dose, and schedule of eltrombopag in the treatment of chemotherapy associated myelosuppression. [Display omitted] [Display omitted] [Display omitted] DisclosuresStrickland:Alexion Pharmaceuticals: Consultancy; Ambit: Consultancy; Baxalta: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; CTI Biopharma: Consultancy; Daiichi Sankyo: Consultancy; Sunesis Pharmaceuticals: Consultancy, Research Funding; Abbvie: Research Funding; Astellas Pharma: Research Funding; Celator: Research Funding; Cyclacel: Research Funding; GlaxoSmithKline: Research Funding; Karyopharm Therapeutica: Research Funding; Sanofi: Research Funding.

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study

IntroductionIn patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue—haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent...

GRADE guidelines system is reproducible when instructions are clearly operationalized even among the guidelines panel members with limited experience with GRADE

ObjectivesThe Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) is a widely used methodology for the development of clinical practice guideline. Although its reproducibility is good for evaluating the quality of evidence, it has not been tested in context of developing recommendations. The objective of this study was to assess the reproducibility of all GRADE factors that determine the direction and strength of a recommendation among the guideline panel members with limited exposure to GRADE methodology. Study Design and SettingThe study was conducted as part of the clinical practice guideline development process of American Association of Blood Banking for the use of prophylactic vs. therapeutic platelet transfusion in patients with thrombocytopenia. The results from the systematic review and meta-analysis for each question were summarized as a GRADE evidence profile. Interrater agreement for all GRADE factors and strength of recommendations was summarized using a weighted kappa statistic with 95% confidence intervals (CI). ResultsEighteen members of the panel participated in the deliberation of making recommendations and completed the online questionnaire. They were given two 1-hour lectures about GRADE. The agreement for all domains was better than chance. The interrater agreement for the domain of quality of evidence was good (kappa value: 0.68; 95% CIs: 0.54, 0.84), and fair for balance of benefit and harms (kappa value: 0.4; 95% CIs: 0.25, 0.57) and use of resources (kappa value: 0.28: 95% CIs: 0.12, 0.42). The interrater agreement was moderate for the GRADE domain of patients' values and preferences (kappa value: 0.44; 95% CI: 0.31, 0.56). The interrater agreement for making a for/against recommendation was good (kappa value: 0.74; 95% CIs: 0.33, 0.91) and fair for strong/weak recommendation (kappa value: 0.39; 95% CIs: 0.18, 0.68). ConclusionsAlthough not all elements of GRADE system had good agreement, the interrater agreement for assessing the quality of evidence and issuing a recommendation of for vs. against among panel members who had limited exposure to GRADE methodology was good. This is probably because GRADE has operationalized these two areas in more detail than other domains. Further operationalization of all GRADE domains such as with the GRADE evidence to decision frameworks would likely improve its reproducibility.

Phase 1b and Pharmacokinetic Study of Idelalisib in Japanese Patients with Relapsed or Refractory (R/R) Indolent B-Cell Non-Hodgkin Lymphoma (iNHL) or Chronic Lymphocytic Leukemia (CLL)

Background: Increased phosphatidylinositol-3-kinase delta (PI3Kd) activity drives proliferation and survival of malignant B-cells and mediates trafficking to lymphoid tissues. Idelalisib, a first-in-class, selective, oral inhibitor of PI3Kd, is approved in combination with rituximab for patients with relapsed CLL and as monotherapy in patients with relapsed/refractory (R/R) follicular lymphoma (FL) in North America and the EU.Methods: Six Japanese patients were enrolled between October 2014 and November 2014. This is an open-label 6+6 study design for continuous dosing of idelalisib 150mg BID in patients with R/R CLL and iNHL until PD or intolerable toxicity. The primary objective was to evaluate the 28-day safety, tolerability and pharmacokinetics of idelalisib and its metabolite GS-563117. The primary endpoint was the incidence of dose-limiting toxicity (DLT) defined as grade 4 hematological toxicities persisting for >14 days, grade ≥3 non-hematological toxicities, grade >3 laboratory abnormalities, red cell transfusion, and a therapeutic platelet transfusion. Key inclusion criteria were: age ≥20 yrs, patient of Japanese ancestry. Key exclusion criteria were known histological transformation to an aggressive histology, history of iNHL or CLL with CNS involvement. Response assessments as per modified Hallek 2008 and Cheson criteria 2007 were performed using CT scans at pre-determined time points by investigators.Results: Baseline characteristics included 3 patients each with CLL (2/3 refractory, 1/3 relapsed) or FL (3/3 refractory), and median age was 64 years (range 49-74). Median number of prior Rx regimens was 3.5 (range 1-6). Prior therapies included bendamustine plus rituximab (67%), R-CHOP (67%), and R-CVP (33%). No Japanese patients experienced a DLT within the 28-day window. The PK of idelalisib and GS-563117 were comparable between Japanese and non-Japanese patients; non-Japanese PK data predicted from preceding Phase 2 and Phase 3 studies. The most common treatment-emergent any grade/≥ grade 3 AEs in increasing frequency were gastritis (33%/0%), pyrexia (33%/0%), transaminases increased (33%/33%), chest pain (17%/0%), decreased appetite (17%/17%), diarrhea (17%/17%), neutrophil count decreased (17%/17%) and common laboratory abnormalities were decreased WBC (50%/17%), decreased neutrophil count (50%/17%), increased ALT (33%/17%), and increased AST (17%/17%). At the time of this analysis, a total of 3 patients experienced serious AEs (50%); decreased appetite, diarrhea, and increased transaminases. Investigator response assessments were 5/6 (83%) patients achieving partial response (PR) and 1/6 (17%) stable disease.Conclusions: Continuous dosing of idelalisib demonstrated a manageable safety profile with promising efficacy in Japanese patients with R/R CLL and FL. The PK of idelalisib and GS-563117 were comparable between Japanese and non-Japanese patients. The study was registered at ClincalTrials.gov (NCT02242045). DisclosuresKinoshita:Gilead Sciences: Research Funding. Fukuhara:Gilead Sciences: Research Funding. Nagai:Gilead Sciences: Research Funding. Izutsu:Gilead Sciences: Research Funding. Kobayashi:Gilead Sciences: Research Funding. Higuchi:Gilead Sciences: Research Funding. Harigae:Gilead Sciences: Research Funding. Tokunaga:Gilead Sciences: Research Funding. Adewoye:Gilead Sciences: Employment, Equity Ownership. Robeson:Gilead Sciences: Employment, Equity Ownership. Sharma:Gilead Sciences: Employment, Equity Ownership. Fukui:Gilead Sciences: Research Funding. Gao:Gilead Sciences: Employment, Equity Ownership. Christenson:Gilead Sciences: Employment, Equity Ownership. Tobinai:Gilead Sciences: Research Funding.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

Platelet transfusion: a clinical practice guideline from the AABB.

The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10×109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20×109 cells/L. (Grade: weak recommendation; low-quality evidence). The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50×109 cells/L. (Grade: weak recommendation; very-low-quality evidence). The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50×109 cells/L. (Grade: weak recommendation; very-low-quality evidence). The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).

Consolidation Therapy Is Associated with Significantly Lower Bleeding Risk Compared to Induction Therapy in Patients with Acute Myeloid Leukemia

Background: Between 2005 und 2010 we conducted a multicenter randomized study comparing a therapeutic and a prophylactic (morning platelet (ptl) trigger < 10/nl) platelet transfusion strategy in patients with hematological disorders. (The Lancet Vol 380, No 9850, pp 1309-16). Briefly, we could show that a therapeutic plt transfusion strategy, where platelets are transfused in clinical stable patients (pts) only if bleeding ≥ WHO grade II occurs is safe in patients after autologous transplantation. In patients with acute myeloid leukemia (AML) we observed significantly more severe bleedings (WHO IV°) with the therapeutic regimen. To proof, if there is a difference in bleeding risk related to the remission status of the patients, we conducted a post-hoc analysis to compare the risk of severe bleeding (WHO III° and IV°) in induction with consolidation therapy.Patients and Methods: We analyzed 175 pts with 175 cycles of induction therapy, 90 with a prophylactic transfusion regimen and 85 cycles with a therapeutic regimen. 131 pts received 268 cycles of consolidation therapy, 155 with a prophylactic and 113 with a therapeutic transfusion strategy.Results: Bleedings WHO III° were neither different between the two strategies nor between induction and consolidation therapy. In contrast, there were significantly more bleedings WHO IV° in induction (7,4%) compared to consolidation therapy (1,5%; p=0,01). In addition, there were significantly more bleedings WHO IV° with the therapeutic regimen (11,8%) compared to the prophylactic strategy (3,3%) in induction therapy (p=0,012). This difference was less pronounced in consolidation therapy. But even in the prophylactic arm most WHO IV° bleedings occurred in pts with more than 10/nl ptl, which shows, that the morning platelet count should not be the only trigger for a platelet transfusion.Conclusions: In consolidation therapy the risk of bleeding is significantly less compared to induction therapy, even with a therapeutic platelet transfusion strategy. During induction therapy the prophylactic strategy should remain the standard of care. The therapeutic transfusion strategy in consolidation therapy will be proven prospectively in an ongoing multicenter study. DisclosuresNo relevant conflicts of interest to declare.

Indications for platelet transfusion in patients with thrombocytopenia.

Platelet transfusion has become a progressively more common and important therapeutic procedure in managing thrombocytopenic patients. Nevertheless, this therapy continues to evolve. Most platelet products are transfused into non-bleeding thrombocytopenic patients. The transfusion “trigger” or threshold for transfusion of these patients is now generally accepted to be 10,000/μL based on the results of a number of studies. However, it is important to emphasise that this “trigger” value generally applies to uncomplicated patients or those who are not febrile, have no infection, or are not being treated with a drug known to damage platelets. Importantly, even with a platelet “trigger” level established at 10,000/μL, platelet transfusion therapy must be individualised to the patient and the clinical situation. As noted above, fever and infection may be correlated with a greater risk of bleeding, but in addition, minor episodes of bleeding may also increase the subsequent risk of clinically significant bleeding; even haemoglobin concentration may play a role in determining bleeding risk. Finally, although prophylactic platelet transfusion is commonly used in the care of thrombocytopenic patients, therapeutic platelet transfusion may represent a reasonable option in managing the bleeding risk of some thrombocytopenic patients. Certainly in the studies by Wandt et al.26,27 and Stanworth et al.28 the use of therapeutic platelet transfusion resulted in an increased bleeding risk. However, in certain populations of patients, the bleeding seen in the therapeutic transfusion programme is generally mild (WHO bleeding category 2 or less). Nevertheless, the studies have repeatedly highlighted the importance of tailoring platelet transfusions to the clinical needs of each patient. While clinical guidelines for platelet transfusion therapy are reasonably well established, a review of the literature clearly indicates that platelet transfusions must be guided by the population of patients under consideration, the clinical conditions of the patients, and perhaps even the resources of the transfusing facility and its ability to respond rapidly to patients’ transfusion needs.

Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products

Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products