Received Platelet Transfusions Research Articles

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

A multicenter study of the risk of major bleeding in patients with and without cirrhosis undergoing percutaneous liver procedures.

Percutaneous liver procedures are frequently performed in patients with abnormal coagulation tests. Current guidelines suggest prophylactic transfusion is not mandatory in all patients with liver disease or cirrhosis, depending on the risk of bleeding. This study aims to describe the incidence and risk of major bleeding after percutaneous liver procedure in patients with and without cirrhosis. This retrospective study includes patients who underwent percutaneous liver biopsy and radiofrequency and microwave ablation of liver lesions at 3 centers in Spain. A transfusion protocol was considered for platelet counts <50,000 and/or international normalized ratio >1.5. The primary outcome was major bleeding. A total of 1797 patients were included in the study, with 316 having cirrhosis (18%) and 1481 without cirrhosis (82%). Among the patients with cirrhosis, 80 were classified as Child A, and percutaneous liver biopsy was the most frequent procedure (86%). Fourteen patients (0.8%) experienced major bleeding, with 0.4% occurring in radiofrequency and microwave ablation and 0.8% in percutaneous liver biopsy. Bleeding occurred in 0.6% of patients with cirrhosis compared to 0.8% in those without ( p = ns). No clinical or procedural variables were associated with bleeding. Twenty-five patients (1.4%) had an international normalized ratio >1.5, and 22 patients (1.2%) had a platelet count <50,000. Only 24% (6/25) of patients with an international normalized ratio >1.5 were transfused with fresh frozen plasma, and 72% (16/22) of those with platelet counts <50,000 received platelet transfusion. Patients with cirrhosis were more frequently transfused (5.9% vs. 1.5%). None of the patients who met the criteria for transfusion experienced major bleeding, regardless of whether they received a transfusion, and none of the patients who had a major bleeding episode met the transfusion criteria. In this cohort, major bleeding after percutaneous liver procedure occurred in <1% of patients, making it a low-risk procedure for patients with and without cirrhosis. Although not uniformly adopted, the current transfusion protocol still led to unnecessary blood product administration.

Platelet transfusion enhances pro-aggregatory status shortly aftercoronary artery bypass grafting (CABG while modulating platelet pro-inflammatory state 1-week post-surgery.

During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study investigates the effects of platelet transfusion on the major pro-aggregatory, pro-inflammatory and immunomodulatory markers of platelets. Platelets from 20 patients, 10 who received platelet transfusion and 10 without, were subjected to flow cytometery where P-selectin and CD40 ligand (CD40L) expressions and PAC-1 binding (activation-specific anti GPIIb/GPIIIa antibody)analysed at five-time points of 24 h before surgery, immediately, 2 h, 24 h and 1 week after surgery. Analysis of intra-platelet transforming growth factor-beta-1 (TGF-β1) was also conducted using western blotting. Patients with platelet transfusion showed increased levels of P-selectin, CD40L and intra-platelet TGF-β1 2-h after surgery compared to those without transfusion (p < 0.05). PAC-1 binding was increased 24 h after surgery in transfused patients (p < 0.05). Given the significant post-transfusion elevation of platelet TGF-β1, P-sel/CD40L reduction in transfused patients a week after was of much interest. This study showed for the first time the significant effects of platelet transfusion on the pro-inflammatory, pro-aggeregatory and immunomodulatory state of platelets in CABG patients, which manifested with immediate, midterm and delayed consequences. While the increased pro-inflammatory conditions manifested as an immediate effect of platelet transfusion, the pro-aggregatory circumstances emerged 24h post-transfusion. A week after surgery, attenuations of pro-inflammatory markers of platelets in transfused patients were shown, which might be due to the immunomodulatory effects of TGF-β1.

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion

Introduction: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. Methods: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/μL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/μL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. Results: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (−0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/μL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). Conclusion: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Chronic liver disease-associated severe thrombocytopenia in Spain: Results from a retrospective study using machine learning and natural language processing

BackgroundPatients with chronic liver disease (CLD) often develop thrombocytopenia (TCP) as a complication. Severe TCP (platelet count<50×109/L) can increase morbidity and complicate CLD management, increasing bleeding risk during invasive procedures. ObjectivesTo describe the real-world scenario of CLD-associated severe TCP patients’ clinical characteristics. To evaluate the association between invasive procedures, prophylactic treatments, and bleeding events in this group of patients. To describe their need of medical resource use in Spain. MethodsThis is a retrospective, multicenter study including patients who had confirmed diagnosis of CLD and severe TCP in four hospitals within the Spanish National Healthcare Network from January 2014 to December 2018. We analyzed the free-text information from Electronic Health Records (EHRs) of patients using Natural Language Processing (NLP), machine learning techniques, and SNOMED-CT terminology. Demographics, comorbidities, analytical parameters and characteristics of CLD were extracted at baseline and need for invasive procedures, prophylactic treatments, bleeding events and medical resources used in the follow up period. Frequency tables were generated for categorical variables, whereas continuous variables were described in summary tables as mean (SD) and median (Q1–Q3). ResultsOut of 1,765,675 patients, 1787 had CLD and severe TCP; 65.2% were male with a mean age of 54.7 years old. Cirrhosis was detected in 46% (n=820) of patients and 9.1% (n=163) had hepatocellular carcinoma. Invasive procedures were needed in 85.6% of patients during the follow up period. Patients undergoing procedures compared to those patients without invasive procedures presented higher rates of bleeding events (33% vs 8%, p<0.0001) and higher number of bleedings. While prophylactic platelet transfusions were given to 25.6% of patients undergoing procedures, TPO receptor agonist use was only detected in 3.1% of them. Most patients (60.9%) required at least one hospital admission during the follow up and 14.4% of admissions were due to bleeding events with a hospital length of stay of 6 (3, 9) days. ConclusionsNLP and machine learning are useful tools to describe real-world data in patients with CLD and severe TCP in Spain. Bleeding events are frequent in those patients who need invasive procedures, even receiving platelet transfusions as a prophylactic treatment, increasing the further use of medical resources. Because that, new prophylactic treatments that are not yet generalized, are needed.

Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Transfusion practices in intensive care units: An Australian and New Zealand point prevalence study

ObjectiveTo describe current transfusion practices in intensive care units (ICUs) in Australia and New Zealand, compare them against national guidelines, and describe how viscoelastic haemostatic assays (VHAs) are used in guiding transfusion decisions. Design, setting and participantsProspective, multicentre, binational point-prevalence study. All adult patients admitted to participating ICUs on a single day in 2021. Main outcome measuresTransfusion types, amounts, clinical reasons, and triggers; use of anti-platelet medications, anti-coagulation, and VHA. ResultsOf 712 adult patients in 51 ICUs, 71 (10%) patients received a transfusion during the 24hr period of observation. Compared to patients not transfused, these patients had higher Acute Physiology and Chronic Health Evaluation II scores (19 versus 17, p = 0.02), a greater proportion were mechanically ventilated (49.3% versus 37.3%, p < 0.05), and more had systemic inflammatory response syndrome (70.4% versus 51.3%, p < 0.01). Overall, 63 (8.8%) patients received red blood cell (RBC) transfusions, 10 (1.4%) patients received platelet transfusions, 6 (0.8%) patients received fresh frozen plasma (FFP), and 5 (0.7%) patients received cryoprecipitate. VHA was available in 42 (82.4%) sites but only used in 6.6% of transfusion episodes when available. Alignment with guidelines was found for 98.6% of RBC transfusions, but only 61.6% for platelet, 28.6% for FFP, and 20% for cryoprecipitate transfusions. ConclusionsNon-RBC transfusion decisions are often not aligned with guidelines and VHA is commonly available but rarely used to guide transfusions. Better evidence to guide transfusions in ICUs is needed.

Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma

Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics. Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes. Of 138 patients who met inclusion criteria, 13.0% (n= 18) reported taking anticoagulants, 16.7% (n= 23) reported taking antiplatelets, and 3.6% (n= 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P= 0.040) and higher rates of palliative care consultations (P= 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group. Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics.

Real-World Treatment Patterns Among Patients with Myelodysplastic Syndromes Initiating Oral Decitabine and Cedazuridine or Intravenous/Subcutaneous Hypomethylating Agents

Introduction: Hypomethylating agents (HMAs) are recommended standard of care for patients with higher-risk myelodysplastic syndromes (HR-MDS). HMA therapies include intravenous (IV) or subcutaneous (SC) decitabine and azacitidine; however, parenteral administration of HMAs has been associated with increased patient burden. The oral HMA decitabine and cedazuridine (DEC-C) was FDA-approved in July 2020 for the treatment of MDS, and offers an alternative to IV/SC HMAs, with similar pharmacokinetic exposure and response rates compared to IV decitabine. This study examined treatment patterns among patients with MDS receiving oral DEC-C compared with IV/SC HMAs in real-world clinical practice. Methods: This was a retrospective analysis using the US Cerner Enviza claims database; medical and prescription claims data for patients were linked to mortality data from Datavant. Adults aged ≥18 years, who were diagnosed with MDS (ICD-10-CM code D46.x; all risk levels), and who had initiated a HMA (≥1 claim; August 1, 2020─August 31, 2022) were included; index date was defined as the first pharmacy or medical claim for DEC-C or IV/SC HMAs, respectively. Patients had variable follow-up after index and were followed until end of enrollment, death, or end of study. Propensity score matching (PSM; 1:1) was performed to balance for confounding factors (age, sex, acute myeloid leukemia [AML] diagnosis, Charlson Comorbidity Index [CCI] score, and red blood cell [RBC] transfusion); adjusted bivariate analysis was used to compare outcomes between treatment groups. Longitudinal persistence was assessed according to the number of cycles of therapy received during follow-up, where a cycle was defined as either 3-10 days of administration of index IV/SC HMA or 1 claim for oral DEC-C, within a 28-day cycle. Results: Of 1569 patients included, 160 (10.2%) received DEC-C and 1409 (89.8%) received IV/SC HMAs. In the DEC-C cohort, median age was 72.5 years and 66.9% were male; in the IV/SC cohort, median age was 69.0 years and 58.2% were male. Two-thirds of patients newly initiated HMAs during the study period (69.4% for DEC-C and 72.2% for IV/SC HMAs); 30.6% of the DEC-C cohort had switched from prior IV/SC HMA treatment. Both groups had high levels of comorbidity; 55.6% of patients in the DEC-C cohort and 58.4% in the IV/SC HMA cohort had CCI scores of ≥3, and 14.4% and 23.8%, respectively, had an AML diagnosis. During the 6-month pre-index period, half (55.3%) of patients in both groups received RBC transfusions, and one quarter (25.9%) received platelet transfusions. After matching, there were 158 patients in each treatment cohort and all covariates included in the PSM were balanced (standardized mean difference &amp;lt;0.2). Median age was 72.0 years and 74.0 years for the DEC-C and IV/SC HMAs matched cohorts, respectively, and 66.5% and 69.6%, respectively, were male. Mean CCI scores were 3.45 for DEC-C and 3.15 for IV/SC HMA groups and 14.6% and 15.8%, respectively, had an AML diagnosis pre index. Longitudinal persistence was comparable between the matched DEC-C and IV/SC cohorts during the first 6 months post-index, with similar proportions receiving the maximum number of treatment cycles (based on a 28-day cycle) at each month following index (73.8% vs 71.1%, 46.5% vs 48.7%, 28.6% vs 24.8%, for 2, 4, 6 months, respectively; Figure). However, a trend towards improved persistence with DEC-C versus IV/SC HMAs was observed in patients receiving treatment beyond 6 months (25.0% vs 17.0%, 18.5% vs 9.0%, 11.4% vs 7.6%, for 8, 10, 12 months, respectively). Mean time to discontinuation of treatment was also numerically higher for DEC-C compared with the IV/SC HMA group (87.7 vs 82.0 days); however, differences were not statistically significant. Conclusions: This study, which is to our knowledge the largest real-world report of oral DEC-C use to date, reveals similar but high levels of disease burden and comorbidities among patients with MDS receiving oral DEC-C and parenteral HMA therapy. Trends in treatment patterns suggest comparable persistence with oral DEC-C and IV/SC HMAs at early stages of therapy and improved persistence with oral DEC-C beyond 6 months. These data support the consideration of oral DEC-C as an alternative to chronic parenteral HMA therapy, with the potential for oral DEC-C to reduce the treatment burden associated with administration of IV/SC HMAs.

Current Management of Pregnant Persons with ITP: Systematic Literature Review

Introduction: Immune thrombocytopenia (ITP) often occurs during pregnancy and thrombocytopenia can worsen as the pregnancy progresses. Thrombocytopenia during pregnancy is significant because of concerns regarding risk of postpartum hemorrhage and neonatal thrombocytopenia. Ideally, patients are managed jointly by hematologists and high-risk obstetricians with a treatment goal to minimize the risk of bleeding complications. The 2019 American Society of Hematology ITP guidelines do not address pregnancy. The 2019 International ITP Consensus Report recommends initial therapy with steroids or intravenous immunoglobulin (IVIG), and patients refractory to initial therapy may need anti-D (Rh(D) positive nonsplenectomized persons), combination therapy, thrombopoietin receptor agonists (TPO-RAs), or rituximab in severe cases. Although the 2019 American College of Obstetricians and Gynecologists (ACOG) guidelines agree with initial management, they disagree with 2nd and 3rd line recommendations stating there is not enough evidence to recommend either anti-D or rituximab during pregnancy and do not mention TPO-RAs at all. Therefore, the purpose of this study was to perform a systematic literature review to describe current management of pregnant persons with ITP. Methods: In March 2023, we conducted a systematic search in the MEDLINE, Embase and Web of Science databases to identify articles on treatment of ITP in pregnancy from 2001-present. Keywords included terms for primary ITP and terms for pregnancy. Inclusion criteria included: 1) English language, 2) humans, and 3) at least 10 pregnant persons in the cohort. Exclusion criteria were: 1) did not contain original data, 2) conference abstracts, 3) unable to separate primary vs secondary ITP, and 4) unable to separate data for only the patients managed after 2001. Three persons independently reviewed articles and performed data abstraction. The online Covidence systematic review management system was utilized to standardize data abstraction and determine consensus. Adverse outcomes were abstracted as reported in the original article. Results: After removal of duplicates, a total of 1396 articles were screened for eligibility, 420 full articles were reviewed and 30 met eligibility criteria (Figure 1). Of the included articles, the majority were retrospective cohort studies (18/30), 6 prospective cohort, 2 case-control, 2 cross-sectional, and 2 clinical trials. These 30 articles represented 3282 pregnant persons aged 16-45 years, with 3868 total pregnancies managed across 14 different countries. Fifty-seven percent of pregnancies (2207/3868) required treatment during the pregnancy and of those treated, 36% (805/2207) only required steroids. Other common treatments included: 17% (372/2207) IVIG + steroids, 14% (307/2207) IVIG only, 11% (232/2207) TPO-RAs, and 10% (225/2207) received platelet transfusions. Only 8 pregnancies were treated with rituximab and 0 with anti-D. Nine articles described management during delivery. The majority (58%; 695/1203) reported no treatment was administered during delivery. When treatment was administered during delivery, it was a platelet transfusion (59%; 302/508) or steroids (40%; 204/508). Only 2 maternal deaths were reported. There were 2 neonatal deaths and 68 intrauterine deaths. Also 7% of the total pregnancies were reported to have a post-partum hemorrhage complication. Conclusion: As expected, pregnant persons with ITP were initially managed with steroids and IVIG. However, results from this study suggest hematologists are comfortable treating pregnant persons with off-label TPO-RAs. Patients were rarely treated with rituximab and 0 were treated with anti-D. Pregnancy in ITP was not without maternal risk as 7% of the pregnancies were complicated by hemorrhage. In comparison, the rate of postpartum hemorrhage in 2019 in the United States was reported to be 4.3% (Corbetta-Rastelli, Obstetrics &amp; Gynecology 2023; 141:152-161). Although despite the hemorrhage rate, there were only 2 maternal deaths. Strengths of this study include the number of countries and pregnancies represented; however, limitations include the country-level differences in access to therapies and differences related to risk of pregnancy complications. The treatment landscape for ITP continues to expand; therefore, guidelines reflecting current management options are critical.

Efficacy and Safety of Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia Refractory to Rhtpo in Patients with Lymphoma

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common cause of chemotherapy dose reductions and treatment delays. With applications of recombinant human interleukin 11 (rhIL-11) and recombinant human thrombopoietin (rhTPO), outcomes of patients with CIT have improved significantly. however，some patients with severe thrombocytopenia still have poor responses to the above therapies. Avatrombopag is an orally administered thrombopoietin receptor agonist and can stimulate thrombopoiesis in haematopoietic stem cells. Avatrombopag has been approved in the USA, Europe, and China for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery. It also has been approved for patients with chronic immune thrombocytopenia who are unresponsive to previous treatments in the USA and Europe. The aim of this study is to evaluate the efficacy and safety of avatrombopag in the treatment of refractory CIT. Methods: The clinical data of 23 lymphoma patients with grade 3/4 CIT unresponsive to rhTPO treatment for 7-10 days were collected from April 2022 to May 2023. All patients received avatrombopag orally at a dose of 40 to 60 mg / day combined with subcutaneous injection of rhTPO (300 U/kg/day). Response (R) was defined as a platelet count≥ 50 × /L, or doubling of the baseline platelet count, and absence of bleeding. Platelet transfusion was allowed when the platelet count was less than 10×109/L or with bleeding events. When the platelet count recovered to ≥100 ×10 9/L or increased 50 ×10 9/L from baseline, treatments of avatrombopag and rhTPO were stopped. Results: The median age of the 23 patients with refractory CIT was 57 (range 17‒83) years. The pathological subtypes were diffuse large B cell lymphoma (DLBCL) (n=10), Burkitt lymphoma (n=4), angioimmunoblastic T-cell lymphoma (AITL) (n=3), follicular lymphoma (FL) (n=2), extranodal NK/T cell lymphoma (ENKTL) (n=1), anaplastic large cell lymphoma (ALCL) (n=1), B-lymphoblastic lymphoma (n=1), and mantle cell lymphoma (MCL) (n=1). The treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) (n=11), Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose methotrexate with cytarabine (n=6), liposomal mitoxantrone-containing regimen (n=4), bendamustine-containing regimen (n=1), and peg-asparaginase-based regimens (n=1). At baseline, 19 patients experienced grade 3 and 4 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet level was 12×10 9/L (range 2‒44×10 9/L). Two patients developed grade 1 bleeding events and one patient occurred grade 2 bleeding events. Nineteen patients received platelet transfusion. After receiving the combination therapy of avatrombopag, 73.9% (17/23)of patients achieved the primary end point of corrected platelet counts (≥50×10 9/L )and were free from platelet transfusion. The median time to response was 11 (range 5‒25) days. No treatment-related adverse events such as elevated aminotransferases, thrombosis, fatigue, fever and dizziness were noticed during administration. Two patients received avatrombopag as secondary prophylactic treatment, and there were no grade 4 thrombocytopenia or bleeding events during subsequent cycles of chemotherapy. Conclusion: Avatrombopag is effective and safe in the management of CIT for lymphoma and it can be used as an alternative / combination treatment for the patients who refractory to rhTPO. The further clinical research is still needed to confirm this conclusion.

Efficiency of Platelet Transfusion in Patients with Moderate-to-Severe Chronic Kidney Disease and Thrombocytopenia.

There have been relatively few studies revealing a decreased platelet count in chronic kidney disease (CKD). Although this hematological abnormality is not as well documented as renal anemia, platelet functions are altered in the uremic environment and there is an increased risk of bleeding. The aim of this study was to assess the effectiveness of the administration of platelet concentrate in CKD based on how patient prognosis was influenced by platelet transfusion therapy. The study monitored 104 patients with CKD and thrombocytopenia who received platelet transfusion during their hospitalization in the period from 2015 to 2021. The complete blood cell count, serum urea and creatinine, and inflammatory status were tested upon admission. The number of transfused platelet units were considered for each patient. A Kruskal-Wallis H test showed that for one transfused platelet unit, the distribution of the number of platelets (×103/µL) was the same across the categories of associated diagnoses, which was seen as possible risk factors for thrombocytopenia, including liver cirrhosis and urosepsis. With a single exception, all patients exceeded the critical threshold of 20 × 103/µL and 14 patients remained under 50 × 103/µL. Even though our patients exceeded the critical threshold of platelet numbers, in patients with multiple comorbidities, severe, uncontrolled hemorrhages could not be prevented in 4.83% of cases.

Efficacy and Safety of Avatrombopag on Thrombocytopenia after Chemotherapy in Acute Leukaemia

Background: Thrombocytopenia following chemotherapy is a common and serious complication that leads to an increased risk of bleeding and poor prognosis for patients with acute leukaemia. Current therapeutic strategies consist of platelet transfusion, recombinant human interleukin-11(rhIL-11) and recombinant human thrombopoietin (rhTPO) injection, but these strategies are not satisfactory for some patients and the treatment remains challenging. Avatrombopag is a novel thrombopoietin receptor agonist, which had been approved for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery in the USA, Europe, and China, and in patients with chronic immune thrombocytopenia who were unresponsive to previous treatments in the USA and Europe. This study aims to determine the efficacy and safety of avatrombopag on thrombocytopenia after chemotherapy of acute leukaemia, and to increase the evidence for clinical use of avatrombopag. Methods: The clinical data of 24 acute leukaemia patients with grade 3/4 chemotherapy-induced thrombocytopenia (CIT) for 3-28 days were collected from February 2022 to February 2023. All patients received avatrombopag orally at a dose of 40 mg / day. Platelet (PLT) transfusion was allowed when the platelet level was less than 20×10 9/L or with bleeding events. If platelet count increased to 100 ×10 9/L or 50 ×10 9/L more than baseline, which was defined as complete response (CR), treatment of avatrombopag was stopped. Results: The median age of 24 patients with CIT was 38 (range 17‒69) years, with 14 patients diagnosed with acute myeloid leukemia (AML), 9 patients diagnosed with acute lymphoblastic leukemia (ALL), and 1 patient diagnosed with mixed phenotype acute leukemia (MPAL). Chemotherapy regiments for patients with AML included decitabine combined with venetoclax (n=5), decitabine combined with arabinoside (n=3), arsenic trioxide combined with retinoic acid (n=3), azacytidine combined with venetoclax (n=2), azacytidine combined with medium-dose arabinoside (n=1). Chemotherapy regiments for patients with ALL included CD19 specific CAR-T cells (n=3), decitabine (n=2), blinatumomab (n=2), IVP (idarubicin, vindesine, and prednisone) (n=1), azacytidine combined with venetoclax and chidamide (n=1). Chemotherapy regiment for the patient with MPAL was decitabine combined with venetoclax (n=1). At baseline, 10 patients experienced grade 3 thrombocytopenia after chemotherapy, while 14 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet count was 19×10 9/L (range 1-47×10 9/L). During the treatment period, 14 patients received platelet transfusion. The median time to reach the CR standard was 6 (range 3-26) days, and no patients stopped treatment due to side effect or drug intolerance. Compared with using avatrombopag before, the levels of platelet count were significantly increased ( P=0.000 1). The optimal platelet count of 22 patients reached the standard of CR after 7 days of drug withdrawal. Conclusion: Avatrombopag is effective on increasing platelet counts in patients with acute leukaemia after chemotherapy, with a good safety profile. It is a suitable therapeutic option for thrombocytopenia after chemotherapy.

Itacitinib for the Prevention of Immune Effector Cell Therapy-Associated Cytokine Release Syndrome: Results from the Phase 2 Incb 39110-211 Placebo-Controlled Randomized Cohort

Introduction: Cytokine release syndrome (CRS) and immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) are common adverse effects following IEC therapy. Janus kinase (JAK) pathways are important for the signaling of several cytokines involved in CRS pathogenesis. Itacitinib is a potent, selective JAK1 inhibitor with broad anti-inflammatory activity. We describe preliminary results from the randomized, placebo-controlled portion of the study evaluating itacitinib 200 mg twice daily (bid) for the prevention of CRS. Methods: This randomized, placebo-controlled portion of the phase 2 Study INCB 39110-211 (NCT04071366) enrolled patients ≥18 years old planning to receive axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma (rrLBCL) and follicular lymphoma (rrFL). Participants received oral itacitinib 200 mg bid beginning 3 days before axicabtagene ciloleucel infusion and continued itacitinib through Day 26. Protocol did not allow tocilizumab for treatment of grade 1 CRS unless CRS did not improve after 72 hours of supportive treatment. Patients who received tocilizumab for grade 1 CRS were not censored. Primary endpoint was incidence of CRS grade ≥2 by Day 14 using American Society for Transplantation and Cellular Therapy grading system. Secondary endpoints included incidence of ICANS by Day 28, duration of CRS and ICANS, and itacitinib safety. Results: 47 patients with rrLBCL were randomized to itacitinib (n=23; median age, 66 [range: 29-80] years; male, 65%) or placebo arms (n=24; median age, 64 [range: 31-79] years; male, 71%). Median (range) number of prior regimens was 2 (1-6) and 1.5 (1-4), respectively. No rrFL patients enrolled in the study. Two (8%) patients in the itacitinib arm received platelet transfusions after Day 28; no transfusions were received in the placebo group. A total of 15 (65.2%) patients in the itacitinib arm developed CRS (grade 1, n=11 [47.8%]) compared with 20 (87.0%) patients in placebo arm (grade 1, n=7 [30.4%]; Figure). No hypotension or hypoxia was observed in patients with grade 1 CRS who received tocilizumab. Grade 2 CRS was experienced by 4 (17.4%) and 13 (56.5%) patients, respectively ( P=0.003; 95% CI: 0.14-0.65). There was no grade 3 or 4 CRS in either arm. Median (range) time to any-grade CRS onset was 2 (0-8) days and 3 (0-9) days, respectively; median (range) duration of grade 2 CRS was 2 (1-8) and 2 (1-5) days. Overall, tocilizumab was used for CRS treatment in 4 (17.4%) patients in the itacitinib arm and in 15 (65.2%) patients in the placebo arm, including 2 and 6 patients, respectively, who received tocilizumab for grade 1 CRS. ICANS occurred in 3 (13%; 95% CI: 3-34) patients in the itacitinib arm and 8 (34.8%; 95% CI: 16-57) patients in the placebo arm (Figure). ICANS grade ≥2 was reported in 2 (8.6%; 95% CI: 1-28) and 5 (21.7%; 95% CI: 8-44) patients, respectively. No grade 4 ICANS occurred in either arm. Median (range) time to any-grade ICANS onset was 5 (4-9) days and 6.5 (2-11) days, respectively; median (range) duration was 2 (2-11) and 3.5 (2-13) days. Persistent grade 3 or 4 thrombocytopenia at Day 28 in the itacitinib arm was reported in 8 (38.1%; [grade 4: n=4]) patients; in the placebo arm in 4 (18.2%; [grade 4: n=0]) patients. Persistent grade 3 or 4 neutropenia at Day 28 in the itacitinib arm was reported in 7 (33.3%; [grade 4: n=3]) patients; in the placebo arm in 3 (13.6%; [grade 4: n=0]) patients. Infections grade ≥3 occurred before Day 28 in 2 (8.7%) patients in the itacitinib arm (urinary tract infection [UTI], n=2) and in 3 (12.5%) patients in the placebo arm (sepsis, n=2; UTI, n=1). There were no fatal adverse events. With a minimum follow-up of 28 days, lymphoma best overall response to axicabtagene ciloleucel showed no difference between the 2 arms. Conclusions: Results from the randomized, placebo-controlled portion of Study INCB 39110-211 have shown prophylaxis treatment with itacitinib 200 mg bid to be well tolerated and resulted in a lower rate and grade of CRS and ICANS after lymphoma treatment with axicabtagene ciloleucel. Incidence of grade 3/4 neutropenia and thrombocytopenia not resolved at Day 28 was higher with itacitinib vs placebo. Rates of severe infections were comparable in both arms. Longer follow-up data on lymphoma response will be available upon presentation. Biomarker analyses comparing the effect of itacitinib on CAR-T cells expansion and function are ongoing.

Developmental Differences between Neonatal and Adult Platelets in Regard to Immune Protein Content and Regulation of Monocyte Inflammatory Responses

Preterm neonates frequently receive platelet transfusions (PTx), owing to their high incidence of thrombocytopenia and bleeding. However, a recent large randomized trial found a significantly higher incidence of death or major bleeding among more liberally transfused preterm neonates. The mechanisms underlying these deleterious effects are unknown, but it has been suggested that they are related to the developmental differences between adult and neonatal platelets, and to a potential “developmental mismatch” occurring when adult platelets (comparatively hyperreactive) are transfused into neonates. While most studies so far have focused on the hemostatic effects of PTx, it is now clear that platelets are key modulators of immune and inflammatory responses. We hypothesized that adult platelets would be more pro-inflammatory than neonatal platelets. To test this hypothesis, we first compared the proteome of resting cord blood (CB, n=9) and adult (n=7) platelets. Using data-independent acquisition mass spectrometry, we identified 4173 high-confidence proteins present in both adult and neonatal platelets. In a principal component analysis, neonatal and adult platelets clustered separately, and 359 proteins were present at significantly different relative abundances between the two groups (≥1.5-fold change, p&amp;lt;0.05). Pathway analysis of the 169 proteins significantly more abundant in the adult platelet proteome revealed enrichment for immune and inflammatory pathways, while neonatal platelets were enriched for pathways involved in metabolic processes. Next, we compared the effects of neonatal and adult platelets on the inflammatory response of human neonatal monocytes. Platelets and monocytes were isolated from healthy adult blood or full-term CB (n=6/group). Platelet P-selectin surface expression was determined by flow cytometry, and key platelet-derived immune regulators (RANTES, β-2 Microglobulin [β2M], and TGF-β) were quantified in the supernatant of resting and activated platelets by ELISA. After washing, neonatal and adult platelets had similarly low P-selectin surface expression levels. Following thrombin activation, P-selectin surface expression was significantly higher in adult than in neonatal platelets (MFI 4010±1645 vs. 1987±816, p=0.04). Thrombin activation increased RANTES and TGF-β release from adult and neonatal platelets to similar levels. In contrast, β2M levels were significantly higher in the supernatant from activated adult compared to neonatal platelets (37.9±10.2 vs 17.9±5.0 ng/mL, p=0.0004). Next, we co-cultured activated adult or neonatal platelets with neonatal monocytes and quantified the pro-inflammatory cytokines IL-8 and MCP-1 (CCL2) in the supernatants after 18 hours. The presence of activated platelets significantly increased IL-8 production from neonatal monocytes compared to monocytes alone, 2.9±1.2-fold when neonatal platelets were added and 4.2±1.8-fold with addition of adult platelets (p=0.01 and p=0.001, respectively). MCP-1 increased to similar levels with the addition of either neonatal or adult platelets. In a regression model, both P-selectin expression and platelet-released β2M levels were significantly associated with monocyte-produced IL-8 levels (p=0.001 and p=0.04, respectively). In summary, we found that proteins related to inflammatory and immune responses are more abundant in adult compared to neonatal platelets, and that activated adult platelets express more P-selectin and release more β2M than neonatal platelets, resulting in higher IL8 production by neonatal monocytes. These findings support the hypothesis that the pro-inflammatory effects of adult platelets might contribute to the increased morbidity and mortality associated with neonatal PTx.

Severe thrombocytopenia induced by tirofiban after percutaneous coronary intervention: a case report

BackgroundTirofiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist used widely in patients subjected to percutaneous coronary intervention. While the usage of tirofiban sets an important clinical benefit, severe thrombocytopenia can occur with use of this agent.Case presentationA 76-year-old Chinese man was admitted with 1-month history of sudden onset of chest tightness. He was diagnosed as having subacute inferior myocardial infarction, and percutaneous coronary intervention was performed. After the procedure, patient received tirofiban at 0.15 µg/kg/minute for 4 h. A blood sample was obtained for a complete blood count; severe thrombocytopenia was reported according to routine orders at our hospital. All antiplatelet drugs including tirofiban, aspirin, and clopidogrel were immediately discontinued. The patient received platelet transfusions and was treated with immunoglobulin G. Two days later, the patient’s platelet count had increased to 75 × 109/L. There was a significant improvement after day 5, and the platelet count was 112 × 109/L. Seven days after the acute thrombocytopenia, he was discharged with normal platelet count.ConclusionsClinicians should be particularly aware of tirofiban-induced thrombocytopenia in routine practice.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

PurposeThrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients.MethodsWe conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.ResultsWe analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42).ConclusionThrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

PB0132 Hemostatic Evaluation of Patients with Thrombocytopenia Receiving Platelet Transfusion using the Total Thrombus Formation Analysis System (T-TAS)

PB0132 Hemostatic Evaluation of Patients with Thrombocytopenia Receiving Platelet Transfusion using the Total Thrombus Formation Analysis System (T-TAS)

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study

BackgroundClinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome.MethodsThis multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS.ResultsBoth groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043).ConclusionsAlthough the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Omics markers of platelet transfusion in trauma patients.

Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.