Patients Received Platelet Transfusions Research Articles

Abstract 058: Outcomes in Patients with Spontaneous Intracranial Hemorrhage Who Underwent Thromboelastography Testing

Introduction In the U.S., intracerebral hemorrhage (ICH) accounts for 10‐15% of all strokes, yet it carries a significantly higher risk of death or long‐term disability. While the Thromboelastography Platelet (TEG PM) mapping tool is well‐established for managing coagulopathy in trauma, organ transplantation, massive transfusions, and ECMO patients, its use in spontaneous ICH is not well understood. This study aims to evaluate patient outcomes in spontaneous ICH cases that received TEG testing compared to those that did not. Method Following IRB approval, we conducted a retrospective review of 215 patients with intracerebral hemorrhage (ICH) from June 2020 to June 2023. Out of these, 160 had spontaneous ICH, with 98 undergoing TEG‐PM testing and 62 not. The primary outcome was to evaluate the frequency of platelet transfusions and complications related to external ventricular drains (EVD). The secondary outcome was to compare discharge outcomes, using discharge status as a proxy for functional recovery, with discharge to home or acute rehab considered a good outcome. Chi‐square tests were performed to analyze differences between the TEG and non‐TEG groups, with all analyses conducted using IBM SPSS Statistics. Results We performed a Mann‐Whitney U test to compare ICH volume and initial National Institutes of Health Stroke Scale (NIHSS) scores between the two groups. The results showed that ICH volume was significantly lower in the non‐TEG‐PM group, with a p‐value of 0.002. The median ICH volume of TEG‐PM group was 13 (IQR 4.0‐36.0), while in non‐TEG‐PM group was 4.35 (IQR 1.0‐19.6). There was no significant difference in the initial NIHSS scores between the groups (p=0.063). In patients who underwent TEG‐PM, 10.2% received platelet transfusion as compared to non‐TEG‐PM group where 0% patients received platelet transfusion with p‐value of 0.009. In TEG‐PM group, 26.8 % patients had EVD placement vs 9.7 % in non‐TEG‐PM group with Odds Ratio 0.29 (0.11‐0.76). There was 1% EVD associated hemorrhage seen in patients of TEG‐PM group as compared to 0% in non‐TEG‐PM. 44.9% of the patients in the TEG‐PM had good discharge outcome as compared to 64.5% in non‐TEG‐PM group with p‐value of 0.1 Conclusion The data indicates that TEG‐PM testing is not a reliable predictor of patient outcomes in spontaneous ICH. Interestingly, patients who underwent TEG‐PM testing received more platelet transfusions compared to those who did not, but this did not impact the discharge outcomes. The ICH volume in both groups were not clinically significant.

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.

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.

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.

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.

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.

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.

Platelet transfusions and predictors of bleeding in patients with myelodysplastic syndromes.

This study aimed to describe the burden of thrombocytopenia, supportive care practices, bleeding complications and predictors of bleeding in MDS patients within a large Australian hospital network, to better understand the use and effectiveness of platelet transfusions in MDS. A retrospective cohort study of patients aged ≥18 years with MDS, chronic myelomonocytic leukaemia or MDS/myeloproliferative overlap neoplasm admitted from 2016 to 2018 was conducted. Data were obtained from hospital medical records. One hundred seventy-nine patients (median age 78 years, 61.5% male) were identified. The median platelet count at first admission was 90 × 109 /L. Twenty-eight (15.6%) patients had severe thrombocytopenia (platelet count <20 × 109 /L), of whom nine (32.1%) received prophylactic platelet transfusions, five (17.9%) received tranexamic acid (TXA), seven (25%) received both platelet transfusions and TXA, and seven (25%) received no treatment. Bleeding events requiring hospitalisation occurred in 20 (11.2%) patients. Bleeding was not predicted by presenting platelet count, TXA use, platelet transfusion or anticoagulant/antiplatelet therapies. Three patients died of bleeding, at varying platelet counts (18, 38 and 153 × 109 /L). Thrombocytopenia is common in MDS. Although guidelines recommend otherwise, prophylactic platelet transfusions were commonly used for severe thrombocytopenia. Despite the majority of patients receiving platelet transfusions and/or TXA, 11% developed major bleeding occurring at a wide range of platelet counts.

In vitro study on the effect of fibrinogen γ-chain peptide-coated ADP-encapsulated liposomes on postcardiopulmonary bypass coagulopathy using patient blood

BackgroundFibrinogen γ-chain peptide-coated, adenosine 5'-diphosphate (ADP)-encapsulated liposomes (H12-ADP-liposomes) are potent hemostatic adjuvants that promote platelet thrombi formation at bleeding sites. Although we have reported the efficacy of these liposomes in a rabbit model of cardiopulmonary bypass coagulopathy, we are yet to address the possibility of their hypercoagulative potential, especially in human beings. ObjectivesConsidering its future clinical applications, we herein investigated the safety of using H12-ADP-liposomes in vitro using blood samples from patients who had received platelet transfusion after cardiopulmonary bypass surgeries. MethodsTen patients receiving platelet transfusions after cardiopulmonary bypass surgery were enrolled. Blood samples were collected at the following 3 points: at the time of incision, at the end of the cardiopulmonary bypass, and immediately after platelet transfusion. After incubating the samples with H12-ADP-liposomes or phosphate-buffered saline (PBS, as a control), blood coagulation, platelet activation, and platelet-leukocyte aggregate formation were evaluated. ResultsPatients’ blood incubated with H12-ADP-liposomes did not differ from that incubated with PBS in coagulation ability, degree of platelet activation, and platelet-leukocyte aggregation at any of the time points. ConclusionH12-ADP-liposomes did not cause abnormal coagulation, platelet activation, or platelet-leukocyte aggregation in the blood of patients who received platelet transfusion after a cardiopulmonary bypass. These results suggest that H12-ADP-liposomes could likely be safely used in these patients, providing hemostasis at the bleeding sites without causing considerable adverse reactions. Future studies are needed to ensure robust safety in human beings.

Altered Fc glycosylation of anti‐HLA alloantibodies in hemato‐oncological patients receiving platelet transfusions

BackgroundThe formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead to platelet refractoriness (PR) and occurs in approximately 5%–15% of patients with chronic platelet support. Interestingly, anti‐HLA IgG levels in alloimmunized patients do not seem to predict PR, suggesting functional or qualitative differences among anti‐HLA IgG. The binding of these alloantibodies to donor platelets can result in rapid clearance after transfusion, presumably via FcγR‐mediated phagocytosis and/or complement activation, which both are affected by the IgG‐Fc glycosylation. ObjectivesTo characterize the Fc glycosylation profile of anti‐HLA class I antibodies formed after platelet transfusion and to investigate its effect on clinical outcome. Patients/MethodsWe screened and captured anti‐HLA class I antibodies (anti‐HLA A2, anti‐HLA A24, and anti‐HLA B7) developed after platelet transfusions in hemato‐oncology patients, who were included in the PREPAReS Trial. Using liquid chromatography‐mass spectrometry, we analyzed the glycosylation profiles of total and anti‐HLA IgG1 developed over time. Subsequently, the glycosylation data was linked to the patients' clinical information and posttransfusion increments. ResultsThe glycosylation profile of anti‐HLA antibodies was highly variable between patients. In general, Fc galactosylation and sialylation levels were elevated compared to total plasma IgG, which correlated negatively with the platelet count increment. Furthermore, high levels of afucosylation were observed for two patients. ConclusionsThese differences in composition of anti‐HLA Fc‐glycosylation profiles could potentially explain the variation in clinical severity between patients.

Prospective Follow-up of Patients with Myelofibrosis (MF) and Treated with Ruxolitinib in France: The Rumycup Study

Introduction MF is a clonal blood disease affecting 1.5 per 100,000 people worldwide. MF is characterized by megakaryocytic proliferation and atypia, usually accompanied by reticulin and/or collagen fibrosis, splenomegaly, anemia, and constitutional symptoms. Current treatments for MF are palliative, aiming to alleviate symptoms and restore quality of life. Ruxolitinib (Jakavi®) is an oral JAK1/JAK2 inhibitor, first in its class, and currently approved in >90 countries for the treatment of splenomegaly or disease-related symptoms in patients with MF. This study aimed to evaluate the use and outcome of ruxolitinib therapy during the first year after initiation in clinical practice. Methods RUMYCUP was a French, multicenter, non-interventional, prospective study. Adult patients with MF primary or secondary to polycythemia vera (PV) or essential thrombocythemia (ET) and for whom a decision was taken to initiate treatment with ruxolitinib, were included in the study. Primary data were collected at inclusion and at 3, 6, 9 and 12 months. The primary objective of this study was to assess ruxolitinib exposure during 11.5 months after treatment initiation. The secondary objectives were to describe patients' characteristics and treatment with ruxolitinib. Results Between Oct-2018 and Sep-2021, 152 patients were enrolled in the study in 49 French centers. Of them, 146 were included in the analysis population and 150 were included in the safety population. Overall, 50.7% of patients (95% CI: 42.3; 59.0) received ruxolitinib for at least 11.5 months, with a higher proportion in patients with splenomegaly at initiation than in those with no or unknown splenomegaly (53.8% vs 37.9%). At inclusion, 58.9% of patients were male, and the mean age was 70.9 years. Half of the patients were diagnosed with primary MF, 33.6% had a post-ET and 15.8% had a post-PV MF. The driver mutations were JAK2V617F in 69.2% of patients, CALR in 11.6%, and MPL in 4.8%. Among patients with available prognostic scores, 30.9% had a high-risk disease, 36.8% and 26.5% had an intermediate 2 or 1 risk disease, respectively, and 5.9% had a low risk disease, based on the International Prognosis Scoring System. At inclusion, 27.4% of patients had hepatomegaly, 32.9% had night sweats, 21.2% had weight loss, and 5.5% had fever. Within the 3 months prior to ruxolitinib initiation, 72.3% of patients did not receive any transfusion of Red Blood Cell (RBC) concentrates, 17.0% had >2 and 10.6% had 1 or 2 RBC transfusions. The median length of the spleen measured by palpation was 8.0 cm below costal margin and the median decrease was of 2.5 cm at Month 12. At inclusion, 58.2% of patients had had at least one previous treatment line and 19.9% two or more lines. As first line, 55.8% of patients received hydroxyurea. During follow-up, <43% of patients received RBC units and <10% of patients received platelet transfusions. Ruxolitinib was initiated at a median dose of 25 mg/day, and the main reasons for starting treatment were splenomegaly (78.1% of patients) and symptoms (58.9%). During follow-up, the dose was increased in 26.7% of patients (mostly for optimization of efficacy), decreased in 14.4% (mostly due to the occurrence of an adverse event [AE], including lack of efficacy) and both increased and decreased in 21.2% of patients. The treatment was temporarily stopped for 20% of patients, for a median 0.5 months. For 27.6% of them, the treatment interruption lasted >21 days. A total of 513 AEs were described in 89.3% of patients. AEs suspected to be related to ruxolitinib were reported in 57.3% of patients, and 58.0% reported 251 serious AEs (SAEs). Overall, 42 SAEs reported in 24 (16.0%) patients led to death. One SAE suspected to be related to ruxolitinib treatment (hemorrhage), led to the death of one patient. The 23 other deaths were not suspected to be related to ruxolitinib treatment and the most frequent SAEs leading to death, were disease progression (5/150 patients) or myelofibrosis and malignant neoplasm progression (3/150), COVID-19 (3/150) and other infections (5/150). Conclusion This 1-year follow-up conducted in France gives a first overview on the exposure to treatment and disease characteristics in patients with MF treated with ruxolitinib in clinical practice. The evaluation in real life conditions showed that half of the patients included in this study maintained ruxolitinib treatment for at least 11.5 months after initiation.

QLTI-07. IDENTIFYING RISK FACTORS FOR PROLONGED TRANSFUSION-DEPENDENT TEMOZOLOMIDE-INDUCED THROMBOCYTOPAENIA IN PATIENTS RECEIVING CONCURRENT CHEMO-RADIOTHERAPY FOR GLIOBLASTOMA (GBM)

Abstract BACKGROUND Temozolomide-induced thrombocytopaenia is a well-recognised clinical issue with significant inter-patient variation. However, knowledge of the extent of the problem and its potential risk factors remains limited. Our aim was to determine the incidence of patients requiring platelet transfusion and ascertain associated risk factors using real-world data. METHODS Data from patients with GBM receiving concurrent temozolomide-chemo-radiotherapy (CRT) from 01/01/18-31/12/2019 retrospectively reviewed. Patients receiving platelet transfusion identified (Local policy: transfusion for platelet count ≤ 30x109/L). Logistic regression and chi-squared tests used to compare variables in patients requiring platelet transfusion and those not. RESULTS 111 patients with GBM received TMZ-CRT (60Gy/30#; 75mg/m2 temozolomide). 12/111 patients received platelet transfusion: 10 during concurrent-CRT and 2 during adjuvant-treatment. Numbers of transfusions: 1-2: 7 patients; 3-4: 2 patients; ≥ 5 transfusions: 3 patients. Median time from platelet count ≥ G3 to ≥ 100 in 11/12 patients: 38 days (range 6-72). 1 did not recover, patient died 84 days following start of TMZ-CRT with thrombocytopaenia. Comparison of the transfused vs the non-transfused cohort shows: transfused: 50% female; non-transfused: 36% female. Mean BSA: transfused: 1.73, SD0.21; non-transfused:1.96, SD0.22 (OR 0.01; 95% CI:0.0003 – 0.16). Mean age: transfused: 57, SD15.8; non-transfused: 58, SD10.7 . Mean baseline platelet count: transfused: 329, SD185; non-transfused: 319, SD117. Mean PTV: transfused: 400, SD115; non-transfused: 414, SD123. There were no statistically significant associations with demographics, age, blood parameters or planning target volume. CONCLUSION This study demonstrates a subset of patients who experience severe and prolonged thrombocytopaenia. Risk factors elucidated are female sex and lower BSA. Large-scale prospective trials evaluating a panel of predictors including concomitant medications, patient MGMT variants and temozolomide-metabolite concentrations would be valuable. Precise stratification of this vulnerable subgroup may permit consideration of temozolomide dose-capping in the future. Careful informed consent with all patients and caution with intensifying treatment under trials is vital presently.

Platelet transfusion in patients with liver cirrhosis cross-talk with neutrophil: Prospective study

IntroductionImmune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. MethodsThis prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. ResultsThere was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CD11b among cirrhotic patients. ConclusionsElective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CD11b on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

Platelet dysfunction after trauma: From mechanisms to targeted treatment.

Platelet dysfunction after trauma: From mechanisms to targeted treatment.

P1366: NEW LYMPHOABLATIVE CONDITIONING REGIME FOR MULTIPLE SCLEROSIS – FIRST RESULTS FROM RUSSIAN PILOT STUDY

Background: Intermediate-intensity chemotherapy (IDCT) followed by autologous transplantation of hematopoietic stem cells (ASCT) is the standard of treatment for the part of patients with hightly aggressive relapse-remitting multiple sclerosis (RRMS). There are several most used conditioning regimens, previous EBMT recommendations recommended the use of ‘intermediate intensity’ regimen namely cyclophosphamide 200 mg/kg with T-cell depleting. However, there are currently no data on the conduct of randomized studies that would compare the effectiveness and toxicity of different regimens. Aims: Comparison toxicity conditioning regimens Cph+R and Flu/Cph+R as a conditioning regimen before auto-HSCT for the treatment of and MS Methods: In active study with retrospective control included 94 patients with MS, median age 43 years; 64 men and 30 women, RRMS – 31 patients, PPMS – 39 patients, SPMS -24 patients. EDSS score was 1.5 – 7.5 (average 4.5). All patients received HDCT and ASCT in NMSC named after N.I. Pirogov (2018 - 2021). Conditioning regimens: Cph200 (cyclophosphamide 200 mg/kg 4 days + Rituximab 500 mg/m2 1 day) – 49 patients, Flu/Cph (Fludarabine 150mg/m2 + 6 days + cyclophosphamide 100 mg/kg 2 days + Rituximab 500 mg/m2 1 day) – 45 patients. Results: Hematologic toxicity of different regimens Cph+R, Flu/Cph+R: Duration of neutropenia was– 7-12 days (average 9.6) in Cph+R group and 3-10 (average 6.3) in Flu/Cph+R group. Duration of thrombocytopenia in Cph+R regimen – 7.7 days, Flu/Cph+R -3.4 days. There are 31 (63%) patients received platelet transfusion in Cph+R group and 6 (12%) patients in Flu/Cph+R group. Anemia Grade II (CTCAE 5.0, 2017) was identified in booth regimens. Anemi grade III was most commonly appear in Flu/Cph+R regime (n=4 – 8%). Range of immunosuppression: The minimal count of lymphocytes was significant lower in Flu/Cph+R group 0,0001 – 0,1 х109/l (average 0.008х109/l), than in Cph+R group witch minimal count of lymphocyte was (0,001 – 0,1 х109/l (average 0.03х109/l) (p<0.05) (pic. 1). Non-hematologic toxicity. Oral mucositis (WHO criteria) was observed at 13 (26%) patients Cph+R group (Grade I - 61,5 %; Grade II - 38,5 %) in Flu/Cph+R 4 (9%) patients (Grade I - 100 %). Enteropathy more common at Cph+R group - 16 % (n=8), Grade I -10%, Grade II – 4%, Grade III – 2%, in Flu/Cph+R – 2 (4%) patients had enteropathy (Grade II). Cardiotoxic effects was observed once at Cph+R group (atrial fibrilation), no cases in Flu/Cph+R group. Hepatic toxicity (CTCAE 5.0, 2017) was observed at 9 (18%) patients Cph+R group (Grade I - 10%; Grade II - 8%) in Flu/Cph+R 9 (20%) patients (Grade I - 15 %, Grade II – 5%). Infection in Cph+R group 13 (26%) patients had infection complications (7 local infections, 6 blood stream infections), in Flu/Cph+R – 5 (10%) patients had infection complications complications -1 local infection, 1 catheter –related infection, 3 neutropenic fever). There are no cases of transplant-related mortality in booth regimes. Summary/Conclusion: The effectiveness of the IDCT method in the treatment of aggressive forms of multiple sclerosis has been proven, at the same time, this method has significant limitations due to high toxicity. Our regime (Flu/Cph+R) showed a significantly deeper lymphodepletion, with less toxicity and a reduced incidence of infectious complications. Thus, this method can be applied to the larger number of patients.

Evaluation and management of platelet transfusion refractoriness.

Platelet transfusion refractoriness (PTR), in which platelet counts do not increase after transfusion, occurs in many patients receiving platelet transfusions. PTR is a clinical condition that can harm patients. The causes of PTR can be divided into two types: immune and non-immune. Most cases of PTR are non-immune. Among immune causes, the most common is human leukocyte antigen (HLA) class I molecules. PTR caused by anti-HLA antibodies is usually managed by transfusing HLA-matched platelets. Therefore, it is important, especially for hemato-oncologists who frequently perform transfusion, to accurately diagnose whether the cause of platelet transfusion failure is alloimmune or non-immunological when determining the treatment direction for the patient. In this review, we discuss the definitions, causes, countermeasures, and prevention methods of PTR.

Platelet transfusion practice and related transfusion reactions in a large teaching hospital.

Platelet transfusion practice varies widely since many aspects of platelet concentrate (PC) use have not been definitively determined. The objectives of this retrospective study were to present platelet transfusion practice and evaluate PC and patient characteristics, as well as their association with transfusion reaction (TR) rate. Platelet transfusions over a 5-year period were analysed regarding PC characteristics (the ABO and RhD compatibility, product type, and storage duration), patient characteristics (most responsible diagnosis, age, and gender), and TR type. A total of 46,351 PCs were transfused: 76.4% whole blood-derived (WBD) and 23.6% single donor apheresis (SDA). Three thousand seven hundred seventy-six patients received platelet transfusions: 24.7% paediatric and 75.3% adult patients, 79.6% outpatients and 20.4% inpatients. As much as 63.1% of all transfused PCs were fresh (stored for≤3 days), 98.0% ABO-identical, and 87.3% of all PCs given to RhD- patients were RhD-. PCs were mainly transfused to haemato-oncology (76.8%) and cardiovascular surgery patients (6.5%). Overall, 84 (0.18%) TRs were reported, with allergic TRs (ATRs) being the most common. Although PC ABO compatibility and storage duration, as well as patient age and gender, showed differences in TR rate, only the use of PCs in platelet additive solution (PAS) showed a statistically significant reduction of TRs (P<0.001). Transfusion practice at the University Hospital Centre Zagreb resulted in almost all patients receiving ABO and RhD identical PCs, and most of them were fresh PCs. The most important factor affecting the incidence of TRs was platelet storage solution. The use of PAS effectively reduced the rate of TRs, particularly allergic TRs.

Contribution of Coagulopathy on the Risk of Bleeding After Central Venous Catheter Placement in Critically Ill Thrombocytopenic Patients.

Single-center retrospective cohort study. Academic mixed ICU in Amsterdam, the Netherlands. Consecutive severely thrombocytopenic (platelet count ≤ 50 × 109/L) patients who underwent central venous catheter placement between February 2016 and February 2020. Central venous catheter placement in patients with both severe thrombocytopenia and severe coagulopathy (international normalized ratio > 1.5 and/or activated partial thromboplastin time > 45 s) versus patients with severe thrombocytopenia and normal or mildly prolonged international normalized ratio and activated partial thromboplastin time. We included 289 central venous catheter placements in 175 patients, 112 in patients with and 172 in patients without severe coagulopathy. Median (interquartile range) platelet count was 27 (16-38) and equal for both groups. There were 44 bleeding episodes at the central venous catheter insertion site (15.5%), of which four (1.4%) were grade 2 and two (0.7%) were grade 3. There were 19 bleeding episodes (17.0%) versus 25 bleeding episodes (14.5%) in the coagulopathy and noncoagulopathy groups, of which one and five were of grade 2 or higher, respectively. After correction for confounders, coagulopathy had no effect on bleeding: odds ratio (95% CI) 0.96 (0.24-3.88). Before central venous catheter placement, 116 (40.8%) patients received platelet transfusion. Bleeding at the central venous catheter insertion site occurred in 19 of 116 patients (16.4%) and 25 of 168 patients (14.9%) who did and did not receive platelet transfusion. After correction for confounders, platelet transfusion had no effect on bleeding: odds ratio (95% CI) 0.73 (0.18-2.83). Coagulopathy was not associated with an increased bleeding risk in severely thrombocytopenic ICU patients undergoing ultrasound guided central venous catheter placement. Prophylactic platelet transfusion in patients with severe thrombocytopenia was not associated with a reduced risk of bleeding.

Journal-related Activities and Other Special Activities at the 2021 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2021 American Society of Anesthesiologists Meeting