Prophylactic Platelet Research Articles

Postoperative bleeding after dentoalveolar surgery in patients with thrombocytopenia—are prophylactic platelet transfusions necessary?

PurposeBenefits of prophylactic platelet (PLT) transfusion before dentoalveolar surgery are unclear. This study investigated the effect of prophylactic PLT transfusions on the incidence of postoperative bleeding (POB) in patients with thrombocytopenia and a PLT count ≤ 75*109/L.MethodsThe cohort in this retrospective study comprised 83 patients with thrombocytopenia ≤ 75*109/L who had undergone dentoalveolar surgery. Exclusion criteria were other coagulation deficiencies or medications that would affect hemostasis. In all, 144 teeth had been removed. POB events were extracted and compared between the group that had received prophylactic PLT transfusion before dentoalveolar surgery and the group that had not.ResultsPOB events were observed in 5 of 83 patients (6.0%) who had a median PLT count of 35*109/L before any transfusion. The group with no postoperative bleeding (NPOB) had a median PLT count of 34*109/L. Two (4.2%) of the 48 patients who had received prophylactic PLT transfusions before dentoalveolar surgery developed POB. Three (8.6%) of the 35 patients who had not received a transfusion experienced POB. The difference between these two groups was not significant (p = 0.646). When two or more teeth were removed in the same session, a significantly higher incidence of POB was observed (p = 0.042).ConclusionsOur data indicate that prophylactic PLT transfusions in thrombocytopenic patients with PLT counts ≤ 75*109/L do not reduce the incidence of POB after dentoalveolar surgery. However, caution is warranted when extracting multiple teeth in the same surgical session since we found this to be significantly associated with an increased risk of POB.

The appropriateness of platelet transfusions in hematological patients and the potential for improvement.

Hematology patients are intensive platelet users. In clinical practice, a substantial proportion of platelet (PLT) transfusions are routinely administered outside the guidelines despite compelling evidence for recommendations. Those unnecessary PLT transfusions are an unjustified extra burden on a scarce healthcare resource and may also be detrimental to the patients. This study aims to evaluate indications and assess the appropriateness of PLT transfusion, as well as to identify common discrepancies and propose modalities for better compliance with guidelines. The audit of all PLT orders for adult hematological inpatients was conducted over 2months. The assessment was performed using guidelines for PLT transfusion. Patient demographic, clinical, and transfusion data were collected from hospital electronic medical records. Based on 286 PLT orders, 344 PCs were transfused to 67 patients: 235 (82.2%) prophylactical due to low PLT count, 34 (11.9%) preprocedural and 17 (5.9%) therapeutic. Overall, 105 (36.77%) PLT transfusions were inappropriate: 78 (33.2%) of all prophylactic PLT transfusions due to low PLT count, 17 (50%) off all preprocedural and 10 (58.8%) of all therapeutical transfusion. The major reason for PLT transfusion inappropriateness was transfusion above the recommended threshold. Double units of PCs were transfused in 36.7% of all PLT transfusions and 32.4% of them were considered inappropriate. Our audit of PLT transfusion practice found a large proportion of inappropriate PLT transfusions. Based on the most common deviations from the guidelines a variety of targeted measures for improvement are proposed.

Prophylactic platelet transfusion and risk of bleeding associated with ultrasound-guided central venous access in patients with severe thrombocytopenia.

Reported risk of bleeding complications after central catheter access in patients with thrombocytopenia is highly variable. Current guidelines recommend routine prophylactic platelet (PLT) transfusion before central venous catheter placement in patients with severe thrombocytopenia. Nevertheless, the strength of such recommendations is weak and supported by observational studies including few patients with very low PLT counts (<20 × 109 /L). This study aims to assess the risk of bleeding complications related to using or not using prophylactic PLT transfusion before ultrasound-guided central venous access in patients with very low PLT counts. This was a retrospective cohort study of patients with very low PLT counts (<20 × 109 /L) subjected to ultrasound-guided central venous catheterization between January 2011 and November 2019 in a university hospital. Bleeding complications were graded according to the Common Terminology Criteria for Adverse Events. A multivariate logistic regression was conducted to assess the risk of major and minor bleeding complications comparing patients who did or did not receive prophylactic PLT transfusion for the procedure. Multiple imputation by chained equations was used to handle missing data. A two-tailed p< 0.05 was considered statistically significant. Among 221 patients with very low PLT counts, 72 received prophylactic PLT transfusions while 149 did not. Baseline characteristics were similar between transfused and nontransfused patients. No major bleeding events were identified, while minor bleeding events were recognized in 35.7% of patients. Multivariate logistic regression analysis showed no significant differences in bleeding complications between patients who received prophylactic PLT transfusions and those who did not (odds ratio 0.83, 95% confidence interval 0.45-1.55, p= 0.567). Additional complete case and sensitivity analyses yielded results similar to those of the main analysis. In this single-center retrospective cohort study of ultrasound-guided central venous access in patients with very low PLT counts, no major bleeding was identified, and prophylactic PLT transfusions did not significantly decrease minor bleeding events.

CREST: clinical bleeding and risk evaluation in hematology-oncology patients: a systematic review and meta-analysis of thromboelastography's role.

Thrombocytopenia and bleeding are common complications of hematologic malignancies. Often, prophylactic platelets are administered to minimize bleeding risk, based on total platelet count (TPC). However, TPC is a poor predictor, and does not provide rapid information. This review presents a novel prospective in the use of point-of-care viscoelastic studies to assess bleeding risk and guide transfusion therapy in a haematological oncological population, where its use can be extended to a ward level as a bedside test. Monitoring TEG maximum amplitude trends may be useful to guide transfusion protocols, especially for patients with total platelet counts ranging 30–100 × 109/l. Fibrinogen assessment in this group of patients may identify other blood components that require replacing to reduce bleeding risk. Normal maximum amplitude parameters for patients with low platelet counts can be a reassuring sign. This meta-analysis serves to remind the reader that absolute platelet quantity does not equate to the quality of clot formation.

Thromboelastography in guiding preventive platelet transfusion in patients with haematologic diseases.

This study analysed the relationships between the main thromboelastography (TEG) parameters, the platelet (PLT) count and clinical bleeding in patients with blood diseases. We explored the threshold of the relevant parameters in the pathological condition of bleeding, aiming to scientifically guide clinical prophylactic PLT transfusion. In total, 268 patients with clear diagnoses of blood diseases and thrombocytopenia were enrolled and divided into five groups, A, B, C, D and E, corresponding to PLT counts of 0-10 × 109 /L, 11-20 × 109 /L, 21-30 × 109 /L, 31-50 × 109 /L and 51-100 × 109 /L, respectively. TEG and routine blood testing were performed simultaneously, the main TEG parameters and the PLT count were analysed, and the thresholds of the main TEG parameters in each group when the patient had bleeding were obtained. The maximum amplitude (MA) in groups A, B and C increased gradually, with a significant difference between each pair of these groups (P < 0.05). In groups A, B, C, D and E, the corresponding MA at the time of bleeding was 43.5 mm, 39.6 mm, 38.0 mm, 35.2 mm and 50.5 mm, respectively, with statistically significant differences (P < 0.05). The MA can be used as a reference indicator for preventive PLT transfusion to a certain extent. When the PLT count is within different ranges, the MA threshold for preventive PLT transfusion also differs. It is recommended that different PLT counts be correlated with different MA thresholds to guide clinical prophylactic PLT transfusion.

Platelet transfusion improves clot formation and platelet function in severely thrombocytopenic haematology patients.

Prophylactic platelet (PLT) transfusion is a common practice in severely thrombocytopenic patients that reduces mortality, but responses to platelet transfusions are variable and difficult to predict in individual patients. In this prospective study, we evaluated the outcome of PLT transfusions in 40 patients with haematological malignancies, linking corrected count increment (CCI) to clot formation and agonist-induced platelet activation after transfusion. The CCI was highly variable between patients and 34% showed no response (1-h CCI < 7,5). Short time since the last PLT transfusion and extended storage time of the PLT product were linked to poor transfusion response, while patient sex, C-reactive protein or the number of chemotherapy cycles prior to transfusion did not influence transfusion outcome. High CCI and good PLT responsiveness to agonist stimulation predicted efficient clot formation in rotational thromboelastometry, but transfusion did not restore poor PLT function in patients to the level of healthy controls. Our study provides new insights into factors affecting PLT transfusion outcome in haematology patients with severe thrombocytopenia, and suggests that the thrombocytopenic environment, or disease-associated factors, may hamper platelet responsiveness.

Could Transfusion be Restricted for Acute Promyelocytic Leukemia in the Era of Diffetentiating Agents?

BACKGROUNDWith the advent of differentiating agents (DA) like all-trans-retinoic-acid (ATRA), and arsenic trioxide (ATO), acute promyelocytic leukemia (APL) has become one of the best prognostic type of acute myeloid leukemia (AML) even in the under-developed countries. In Myanmar, APL is recognized as a common form of AML and managing APL in the resource limited setting particularly for aggressive transfusion support according to current guidelines is difficult and therefore transfusion requirement of APL treated in our center were analyzed with an aim to find evidence for restrictive transfusion policy. MATHODSCases of APL complicated by disseminated intravascular coagulation (DIC) treated during November 2014 to April 2017 were retrospectively reviewed in this study. All cases were treated with combined ATRA and ATO and conventional chemotherapy was added in high risk patients and those who developed rapid rise in white cell counts. Recommended target platelet count of 30-50 x 109/L and fibrinogen level of 100-150 mg/dl were maintained only for WHO grade 3 to 4 bleeding while the rest were transfused with platelet target of 20 x 109/L and fixed dose of FFP 2 -4 units per day until bleeding subsided. Prophylactic platelet was given for counts below 10 x 109/L. RESULTSAmong 33 APL admitted during two and half year's period, 29 presented with evidence of DIC, of them 4 had already developed intracerebral haemorrhage at presentation and died within 24 hours. In remaining molecularly confirmed 25 patients with APL, 14 males and 11 females, with median age of 28 years (range 12 -58) with initial performance status of 3 to 4 in 8 cases (32%) were classified as low, intermediate and high risk in 1 (4%), 13 (52%) and 11 (44%) cases respectively. Presenting blood counts were median hemoglobin - 5.9 mg/dl (3.2 - 10.6), median white cell count 7.23 x 109/L (0.43 - 110.8) and median platelet count 29 x 109/L (2 - 121). Regarding coagulation profile median PT - 15.6 second (9.9 - 21), median APTT - 28.4 second (20 - 46), median fibrinogen 160 mg/dl (82 - 900) and median D-Dimer - 8700 ng/ml (1917 - 19166). Median lowest platelet was 6 x 109/L (2 - 37) and median days of platelet count less than 10 x 109/L and less than 20 x 109/L were 4 days (0 - 10) and 8 days (2 - 26) respectively. Median number blood products transfused were of 6 units (3 - 12) of red cell, 10 units (6 - 15) of platelets and 10 unit (4 - 24) of FFP in total for each patient. Most bleeding and DIC subsided within first week and there were no haemorrhagic death during induction. CONCLUSIONRestricted transfusion policy may be possible in APL provided close monitoring of clinical and laboratory parameters and transfusion of blood products are tailored according to the risk and clinical condition. DisclosuresNo relevant conflicts of interest to declare.

Quality of evidence-based guidelines for platelet transfusion and use: A systematic review.

Guidelines for platelet (PLT) transfusion are an important source of information for clinicians. Although guidelines intend to increase consistency and quality of care, variation in methodology and recommendations may exist that could impact the value of a guideline. We aimed to determine the quality of existing PLT transfusion guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and to describe the inconsistencies in recommendations. A systematic search was undertaken for evidence-based guidelines from January 1, 2013, to January 25, 2019. Citations were reviewed in duplicate for inclusion and descriptive data extracted. Four physicians appraised the guideline using the AGREE II instrument and the scaled score for each item evaluated was calculated. The protocol was registered in PROSPERO. Of 6744 citations, 6740 records were screened. Seven of 28 full-text studies met the inclusion criteria. The median scaled score (and the interquartile range of the scaled score) for the following items were as follows: scope and purpose, 94% (8%); stakeholder involvement, 63% (18%); rigor of development, 83% (14%); clarity of presentation, 94% (6%); applicability, 58% (20%); and editorial independence, 77% (4%). Overall quality ranged from 4 to 7 (7 is the maximum score). Inconsistent recommendations were on prophylactic PLT transfusion in hypoproliferative thrombocytopenia in the presence of risk factors and dose recommendations. Inconsistencies between guidelines and variable quality highlight areas for future guideline writers to address. Areas of specific attention include issues of stakeholder involvement and applicability.

Trends in platelet distributions from 2008 to 2017: a survey of twelve national and regional blood collectors.

This multi-national study evaluated changes in platelet (PLT) unit distributions at 12 national or regional blood collectors over a 10-year period. Data on the total number of PLT distributions, the collection method, that is apheresis vs whole blood-derived (WBD), the PLT unit characteristics and post-collection modifications were obtained from 12 national or regional blood collectors from 2008 through 2017. Individual WBD PLT units were converted to apheresis equivalent units (i.e. a dose of PLTs) by dividing by 4, the typical pool size; WBD units that were pooled before distribution were counted as a single dose. Overall at these 12 blood collectors, the total number of PLTs distributed in 2008 was 1373200, which rose by 10·2% to 1513803 in 2017. The Japanese Red Cross, which distributes only apheresis PLTs, had a 13·4% increase in the number of distributions between the years 2008 and 2017, while the other 11 blood collectors combined demonstrated a 6·8% increase in distributions between these two years. Between the years 2008 and 2017, the changes in the proportion of apheresis, platelet-rich plasma and buffy coat PLT distributions were -29·9%, -70·7% and 80·0%, respectively. The number of PLT distributions increased during the 10-year study period despite prophylactic PLT transfusion thresholds having remained fairly consistent over the last decade. Perhaps this increase is in part driven by increased administration of platelets to patients with massive haemorrhage or an increase in stem cell transplantation. The use of buffy coat PLTs is increasing at these collectors.

Restrictive Transfusions in the Era of Pathogen-Inactivated Platelets: A Single Center Experience

Introduction Blood management and infectious disease mitigation are essential for success with allogeneic stem cell transplant (alloSCT). We sought to investigate the safety profile of a proactive infection mitigation strategy with the use of pathogen-inactivated (PI) platelets (PLT) during the alloSCT peri-engraftment period in the era of restrictive blood transfusion. Methods We retrospectively analyzed data from patients undergoing alloSCT that received prophylactic red blood cell (RBC) and PLT transfusion triggered by a hemoglobin of 8 g/dL and PLT count of 15,000 PLT/mL. When available, PI PLT (non-irradiated) were used starting November 2016 until March 2018 (study timeframe). Statistical analysis was performed using SAS 9.4 (Cary, NC). Patients characteristics and clinical parameters were summarized using mean and standard deviation or median and range for continuous data, and frequency and percentage for categorical data. Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS) from day of transplant. A two-sided logrank test was used to compare across strata using p Results Sixty-eight patients received alloSCT. Median age at transplant was 55 years (range [R], 18-73). Peripheral blood stem cells were the graft source in all but one patient. Donor source was a matched related, 10/10 matched unrelated (MUD), 9/10 MUD and haploidentical donor in 30.9%, 44.1%, 2.9%, and 22.1% of cases, respectively. Myeloablative conditioning was used in 45.6% of patients. Indication for alloSCT was a myeloid or lymphoid disorder in 64.7% and 35.3% of cases. Median time to neutrophil and PLT engraftment was 12 (R, 10-35) and 12 days (R, 8-120), respectively. Pre-alloSCT RBC alloimmunization was present in 11.8% of patients. Cumulative incidence of grades II-IV acute and chronic graft-versus-host disease (GVHD) was 20.6% and 22.1%, respectively. PI PLT were used in 73.5 % patients. There were no cases of transfusion associated graft failure (GF) or GVHD. Bacteremia occurred in 10.0% and 22.1% of patients by 30 days and 100 days post-alloSCT, respectively, and were both associated with worse OS (both p Conclusions Restrictive prophylactic transfusion thresholds in alloSCT recipients is feasible. Limited PI PLT transfusion was not associated with transfusion-attributable GVHD, GF or infectious complications. Future prospective studies should determine the short term hemostatic efficacy and long term post-alloSCT outcomes with restrictive transfusion criteria in an era of expanding PI product use.

Risk of bleeding after ultrasound-guided jugular central venous catheter insertion in severely thrombocytopenic oncologic patients

IntroductionWe sought to assess the incidence and risk factors of bleeding after ultrasound-guided internal jugular (USGIJ) catheter insertion in severely thrombocytopenic cancer patients, as safe platelet (PLT) count threshold remains controversial. MethodsRetrospective study of 52 patients with hematologic malignancies and severe thrombocytopenia who underwent USGIJ catheter insertion between 2014 and 2016. Group A included patients with prophylactic PLT transfusion and Group B without. Statistical analysis was performed. ResultsGroup A included 28 patients and Group B 24. Baseline characteristics were equally distributed. Median catheter size was 12 Fr and tunneled in 20/52 patients. Median PLT count was not statistically different between the groups, before transfusion and after the procedure. Postoperative minor bleeding occurred in 10/52 patients, similar between groups. Lower PLT count, larger catheter caliber and trend for AML diagnosis were identified as risk factors for bleeding. Age, gender, BMI, renal dysfunction and tunneled insertion were not significant. ConclusionIncidence of minor bleeding is low in severely thrombocytopenic patients after USGIJ catheter insertion. Prophylactic platelet transfusion may be reserved for patients with identified risk factors.

Preprocedural platelet transfusion for patients with thrombocytopenia undergoing interventional radiology procedures is not associated with reduced bleeding complications.

Platelet (PLT) transfusion before interventional radiology procedures is commonly performed in patients with thrombocytopenia. However, it is unclear if PLT transfusion is associated with reduced bleeding complications. This is a retrospective cohort study of adults undergoing interventional radiology procedures between January 1, 2009, and December 31, 2013. Baseline characteristics, coagulation variables, transfusion requirements, and procedural details were evaluated. Propensity-matched analyses were used to assess relationships between PLT transfusions and the outcomes of interest, including a primary outcome of periprocedural red blood cell (RBC) transfusion during the procedure or within the first 24 hours after procedure. A total of 18,204 participants met inclusion criteria, and 2060 (11.3%) had a PLT count of not more than 100×109 /L before their procedure. Of these, 203 patients (9.9) received preprocedural PLTs. There was no significant difference in RBC requirements between those receiving or not receiving preprocedural PLTs in propensity-matched analysis (odds ratio [OR],1.45; 95% confidence interval [CI], 0.95-2.21; p=0.085). PLT transfusion was associated with increased rates of intensive care unit admission (OR [95% CI],1.57 [1.07-2.32]; p=0.022). In patients with thrombocytopenia undergoing interventional radiology procedures, preprocedural PLT transfusion was not associated with reduced periprocedural RBC requirements. These findings suggest that prophylactic PLT transfusions are not warranted in nonbleeding patients with preprocedural PLT counts exceeding 50×109 /L. Future clinical trials are needed to further define relationships between prophylactic PLT administration and bleeding complications, especially at more severe levels of thrombocytopenia or in the presence of PLT dysfunction.

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.

Optimal transfusion practices after allogeneic hematopoietic cell transplantation: a systematic scoping review of evidence from randomized controlled trials.

Integrating evidence from randomized controlled trials (RCTs) into patient care is needed to optimize patient outcomes. Transfusion support during allogeneic hematopoietic cell transplantation (alloHCT) is a cornerstone of essential supportive care, yet optimal transfusion practices remain unclear. A scoping review of RCTs in alloHCT was conducted and 14 full-length articles on transfusion practice were identified that reported clinical outcomes after alloHCT. Eight RCTs compared various interventions related to platelet (PLT) transfusion, addressing product storage duration, dosage, and threshold for transfusion. Restrictive prophylactic PLT transfusion strategies were successful at reducing PLT consumption without impacting clinical outcomes. One study, however, reported increased bleeding associated with a strategy whereby patients did not receive prophylactic PLT transfusions. One study of thrombopoietin was associated with reduced PLT transfusion events but no difference in clinical outcomes compared to placebo. Six RCTs examined the utility of recombinant erythropoietin (EPO) in reducing red blood cell (RBC) transfusion dependence. Four trials reported an increase in hemoglobin levels while five studies demonstrated a reduction in RBC utilization; however, clinical outcomes were variably reported and no differences were identified. There were no RCTs examining RBC transfusion strategies, plasma transfusion, or plasma-derived protein administration. Prophylactic PLT transfusion when PLTs are fewer than 10×109 /L can prevent bleeding and is consistent with recent guidelines. Thrombopoietin and EPO can reduce transfusion requirements; however, potential safety concerns remain and the lack of improvement in clinical outcomes and high cost may limit use. Additional RCTs are needed, particularly with regard to RBC transfusion thresholds, to refine best practices after alloHCT.

Fibrinolysis Times As Outcome Measures Using ROTEM with Tpa-Induced Fibrinolysis in Chemotherapy Induced Thrombocytopenia

Background: Despite prophylactic platelet (PLT) transfusions, used to prevent bleeding in chemotherapy induced thrombocytopenia(CIT), some patients will still bleed, whereas others are spared even without PLT transfusion. Little research has been done on (hyper)fibrinolysis as a risk factor for bleeding in CIT. In this study a tPA-induced fibrinolysis in ROTEM was analysed to gain more insight in clot formation and clot lysis times in patients with CIT before and after PLT transfusions.Aim: to study clot vulnerability for fibrinolysis in CIT patients with tPA-ROTEM.Method: patients, older than 18 years, treated for a hematological malignancy and receiving a prophylactic PLT transfusion for thrombocytopenia were included. Blood was collected before PLT transfusion (baseline) as well as 1 hour and 24 hours after transfusion. A modified, EXTEM based,ROTEM in the presence of tPA was used to study the occurrence of fibrinolysis. The maximum clot firmness (MCF) and the time to maximum clot firmness (MCF-t) were determined. Also, 100-10% lysis times (A), 100-85% lysis times (B) and 85- 10% lysis times (C) were calculated. Reference values for the tPA-ROTEM were obtained from 40 healthy volunteers.Results: patient characteristics are shown in table 1. Baseline platelet counts and fibrinogen concentrations were median 6,000/mcL and 4,6 g/L, respectively (table 2). In the tPA-ROTEM a significant increase in MCF, MCF-t, 100-10% LT and 100-85% LT after transfusion was observed. The MCF remained significantly increased after 24 hrs (table 2). When baseline was compared to the healthy volunteers, the MCF, MCF-t were remarkably reduced in the CIT patients. The 100 -10% lysis time was significantly shorter in patients with CIT ( (27,4 versus 34,4 minutes, (P=0.020) (table 3), mainly due to a shorter 100 -85% LT (11.5 versus 17.9 (P<0,001). There were no differences in the 85 - 10% lysis times. A positive, moderate strength correlation was found between the 100-85% lysis times and fibrinogen concentrations (R=0,499 (P=0,035)).Conclusion: Patients with CIT have a shorter lysis times as measured with tPA-ROTEM than healthy volunteers, mainly occurring during the first phase (100-85%) of fibrinolysis. Higher fibrinogen concentrations were associated with a longer duration of the initial phase. Lysis times outcomes in tPA-ROTEM may be applicable in clinical trials assessing PLT transfusions.Table 1Patient characteristics:N=20SDMin- maxAge55 (mean)1323-72Men (%)10 (50%)Diagnosis9 Acute myeloid leukaemia4 Multiple myeloma4 Non-Hodgkin Lymphoma3 OtherTreatment7 Induction therapy (35%)13 Consolidation therapy and stem cell transplantation (65%)Table 2Results from baseline, 1h and 24h measurements (all as median)Baseline n=181hN=1924hN=18Healthy volunteersN=40Reference valuesPlatelet Count median*109/L6*#33*#21*#173150-400 x109/LFibrinogenmedian(g/L)4.58#4.40#4.64*#3.181.70-4.00Maximum Clot Firmnessmm23 #38*#34*#59Time to Maximum Clot FirmnessMin.11.5#15.7*15.3#18.2Lysis Onset TimeMin.23.0#29.7*#28.3#36.1Lysis TimeMin.38.9#44.4*#44.6#52.6* = P<0,05 versus baseline.# = P=<0,05 versus Healthy volunteers.Table 3Differences in lysis time speed between baseline measurement and healthy volunteersUnitPatient group baselineHealthy volunteersMean differenceP-value100 - 10% lysis timeMin.27.434.470.020100 - 85% lysis timeMin.11.517.96,4<0.00185 - 10% lysis timeMin.15.015.30,30.705 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

North American Cooperative Group Members' Patterns of Blood Products Transfusion for Patients with Acute Leukemia

Background. Transfusion of blood products is an integral component of the management of patients with acute leukemias. However, high-quality evidence and clinical trial data to support specific practices of blood product transfusion in this population are limited. We hypothesized that there is wide variation in blood product transfusion practices among providers in North America who manage patients with acute leukemia.Methods. A 30-question web-based survey about transfusion practices was emailed to members of the Eastern Cooperative Oncology Group (ECOG)-ACRIN Cancer Research Group, Alliance for Clinical Trials in Oncology (Alliance), and the Southwest Oncology Group (SWOG), and the Cancer Trials Support Unit (CTSU) on 7/6/2015 with 4 subsequent weekly reminders. The distribution list included 9,859 recipients, of whom at least 741 were providers who treated patients with acute leukemia. Responses were anonymous, and the survey distribution was approved by the respective cooperative group chairs. Descriptive statistics were used to analyze the data.Results. Of 254 responses received, 113 were excluded as they were returned by recipients not directly treating patients with acute leukemia. Another 30 responses were excluded due to incomplete data, leaving 111 responses (43.7%) eligible for the primary analysis. Of those, 109 responders were from North America representing 83 institutions in 33 states and the province of Ontario. Eighty-four of the included responders (75.7%) were physicians, and 44 (39.6%) were females. Median age of responders was 44 years (range, 26-76). A hemoglobin (Hb) level of ≤7 g/dL was the most commonly used threshold (44%) for red blood cell (RBCs) transfusions to asymptomatic stable hospitalized patients, followed closely by 8 g/dL (38%) (Figure 1). In the outpatient setting, the most commonly reported threshold was 8 gm/dL (49%) (Figure 1). Most providers reported that they "always" use leukocyte-reduced (93%) and irradiated (79%) RBCs. A platelet level of 10,000/µL was the threshold for platelet transfusions in the stable non-bleeding hospitalized patients cited by the majority of responders (76%) (Figure 2). This platelet level remained the most common threshold for platelet transfusions for non-bleeding patients in the outpatient setting (49%), although 31% of responders reported a higher threshold of 20,000/µL. A preference for single-donor apheresis platelets was reported by 81% respondents, and 57% use these products exclusively. Most providers (70%) reported always using irradiated platelets. With respect to cryoprecipitate and plasma infusions, nearly half of the respondents reported a threshold fibrinogen level of 100 mg/dL as a trigger for administering a product to a stable non-bleeding patient (Figure 3). The most commonly reported platelet threshold for performing a bone marrow biopsy (BMB) was 10,000/μL (69% of responders), followed by 20,000 (21%), 50,000 (6%), and 30,000 (4%). Therapeutic anticoagulation was held by most responders (80%) before performing a BMB. Most responders (73%) reported a platelet level of 50,000/µL as the lowest level for performing a lumbar puncture (LP) without prophylactic platelet transfusion.Conclusions. This survey demonstrates wide variability in blood product transfusion patterns among providers who treat patients with acute leukemias. A platelet level of 10,000/µL is the most common trigger for platelet transfusions for stable non-bleeding patients in both inpatient and outpatient settings. This, along with a platelet threshold of 50,000/µL for performing an LP, appear to be most widely accepted practices. Our findings emphasize the need to obtain high-quality data to develop consensus evidence-based guidelines for transfusion practices in acute leukemia with the goal of limiting unnecessary transfusions without compromising patient outcomes. [Display omitted] [Display omitted] [Display omitted] DisclosuresSekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Steensma:Onconova: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Prebet:CELGENE: Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding. Stone:Merck: Consultancy; AROG: Consultancy; Celgene: Consultancy; Sunesis: Consultancy, Other: DSMB for clinical trial; Abbvie: Consultancy; Novartis: Research Funding; Juno: Consultancy; Amgen: Consultancy; Roche/Genetech: Consultancy; Celator: Consultancy; Agios: Consultancy; Karyopharm: Consultancy; Pfizer: Consultancy. Erba:GlycoMimetics; Janssen: Other: Data Safety & Monitoring Committees; Sunesis; Pfizer; Daiichi Sankyo; Ariad: Consultancy; Millennium/Takeda; Celator; Astellas: Research Funding; Seattle Genetics; Amgen: Consultancy, Research Funding; Novartis; Incyte; Celgene: Consultancy, Patents & Royalties. Barbarotta:Celgene, BMS, Novartis: Speakers Bureau. Gore:Celgene: Consultancy, Honoraria, Research Funding.

Bronchoscopy can be done safely in patients with thrombocytopenia

Prophylactic platelet (PLT) transfusions are often administered to patients before bronchoscopy or bronchoalveolar lavage (BAL) to prevent bleeding. There is a paucity of data to validate this approach, with a commonly suggested PLT transfusion threshold of fewer than 50 × 10(9) /L, largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in patients with thrombocytopenia undergoing bronchoscopy. We identified 150 consecutive patients with PLT counts of not more than 100 × 10(9) /L who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. The British Thoracic Society (BTS) guidelines were used to categorize bleeding associated with bronchoscopy. Infection (40%) was the primary indication for bronchoscopy with BAL. Fifty-eight of 89 (65%) patients with baseline PLT counts of not more than 50 × 10(9) /L received prophylactic transfusions compared to 8% of those with PLT counts of more than 50 × 10(9) /L. The PLT count did not increase to more than 50 × 10(9) /L in many patients who received transfusions. Seventy-two patients had counts of less than 50 × 10(9) /L at the time of bronchoscopy, with 15 patients having counts of less than 20 × 10(9) /L. Only one patient with a PLT count of 61 × 10(9) /L had bleeding that required continuous suctioning but then resolved spontaneously (termed "mild bleeding" by BTS criteria). Bloody lavage that resolved spontaneously without continuous suctioning (termed "no bleeding" by the BTS criteria) was observed in nine (6%) patients. The very low incidence of bleeding complications from bronchoscopy with or without BAL even in patients with PLT counts of not more than 30 × 10(9) /L (no episodes of clinically significant bleeding in 35 patients) demonstrates that bronchoscopy can be done safely in patients with severe thrombocytopenia.

Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial.

This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 10(9) /L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients. Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables. Across the whole trial no prophylaxis saved costs compared to prophylaxis: -$1760 per patient (95% confidence interval [CI], -$3250 to -$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: -$110 per patient (95% CI, -$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: -$5686 per patient (95% CI, -$8580 to -$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to -$941 per patient (p = 0.21) across the whole trial and -$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup. It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted.

Impact of prophylactic platelet transfusions on bleeding events in patients with hematologic malignancies: a subgroup analysis of a randomized trial.

A recent randomized trial compared a policy of no prophylaxis with a policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10 × 10(9) /L in patients with hematologic malignancies. The results suggested the effectiveness of prophylactic PLT transfusions may vary according to patient diagnosis and treatment plan. This article presents full subgroup analyses and compares treatment effects between autologous hematopoietic stem cell transplantation (autoHSCT; n = 421) and chemotherapy/allogeneic HSCT (chemo/alloHSCT; n = 179) patients. Prespecified subgroup analysis found that the reduction in proportion of patients experiencing WHO Grade 2 to 4 bleeds (main trial outcome) seen in the prophylaxis arm was of greater magnitude in chemo/alloHSCT than autoHSCT patients (interaction p = 0.04). Analysis of secondary outcomes showed a shorter time to first bleeding episode with no prophylaxis in the chemo/alloHSCT group (hazard ratio, 1.84; 95% confidence interval CI, 1.21-2.79; p = 0.004) compared to the autoHSCT group (hazard ratio, 1.12; 95% CI, 0.85-1.48; p = 0.4; interaction p = 0.08). The increased number of days with Grade 2 to 4 bleeds with a no-prophylaxis policy was similar in chemo/alloHSCT (rate ratio, 1.89; 95% CI, 1.10-3.26) and in autoHSCT patients (rate ratio, 1.43; 95% CI, 1.04-1.97). Both subgroups showed significant reductions in PLT transfusions with a no-prophylaxis strategy. There is evidence that the effectiveness of prophylactic PLT transfusions may differ between subgroups, with chemo/alloHSCT patients receiving prophylactic PLT transfusions appearing to show a greater reduction in bleeding outcomes compared to patients following a no-prophylaxis policy.

Open aortic valve replacement in a patient with Glanzmann's thrombasthenia: a multidisciplinary strategy to minimize perioperative bleeding

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder in which the platelet (PLT) glycoprotein IIb/IIIa complex is either deficient or dysfunctional. In its most severe form, GT may result in spontaneous bleeding, although most cases are first detected in the setting of an invasive procedure. A 59-year-old male with Type I GT and a history of transfusion reactions to PLT infusions developed severe aortic stenosis secondary to bicuspid valve disease. He successfully underwent open aortic valve replacement with cardiopulmonary bypass without perioperative bleeding complications. A multidisciplinary team (anesthesia, hematology, cardiac surgery, and transfusion medicine) was established to optimize perioperative hematologic management. Bleeding risk was assessed given the patient's prior history and a dosing timeline for administration of blood products and recombinant clotting factors was established. Successful management was achieved during the operation by prophylactic administration of HLA-matched PLTs and Factor VIIa. Prophylactic PLT administration was continued through the immediate postoperative period and no bleeding complications occurred. Thromboelastograms (TEGs) were used in conjunction with traditional hematologic laboratory analysis to optimize clinical management. Patients with GT requiring cardiac surgical procedures are at high risk for perioperative bleeding complications. This case report illustrates the importance of multidisciplinary planning, TEG analysis, and the judicious use of recombinant factors to minimize operative bleeding risk.