Thrombocytopenic Patients Research Articles

Thrombocytopenia and its effect on mortality and morbidity in the intensive care unit

Background/Aim: Thrombocytopenia is a common hematological abnormality among patients in the intensive care unit (ICU). The development of thrombocytopenia in the ICU usually indicates severe organ system dysfunction rather than a primary hematological disorder. We aimed to determine the incidence, causes, and clinical results of thrombocytopenia in patients followed up in ICU. Methods: In this retrospective cohort study, 165 patients who were followed up in the ICU with thrombocyte counts below 150,000 /uL were included and causes of thrombocytopenia, along with its effects on mortality and intensive care stay were investigated. Results: Thrombocytopenia was determined in 30.1% of the patients in the ICU. The cause of thrombocytopenia was sepsis in 33 (20.0%) of the patients and disseminated intravascular coagulation (DIC) in 20 (12.1%) patients. During the study period, 115 (69.7%) of 165 thrombocytopenic patients and 173 (45.1%) of 383 patients without thrombocytopenia died. Mortality was significantly higher in patients with thrombocytopenia. Mortality significantly increased when platelet count decreased, even with similar APACHE II scores. Conclusion: The most common causes of thrombocytopenia in the ICU were sepsis and DIC. Thrombocytopenia is common in the ICU and increases mortality rates.

Endothelial Activation and Immune Thrombocytopenia: An Engagement Waiting for Consolidation.

Immune thrombocytopenia (ITP) appears to be a heterogeneous disease. In some patients, autoimmunity may be associated with an inflammatory process, and in other patients, low platelets may interfere with other aspects of the coagulation system. Either may predispose to thrombosis or bleeding. Further investigation of the interactions of platelets, with inflammatory cytokines and endothelial biomarkers, may help us to better understand the disease, and to recognize those patients at risk of bleeding, or conversely thrombosis. The aim of this work is to estimate von Willebrand factor (vWF) and vascular cellular adhesion molecule (V-CAM) serum levels in adult immune thrombocytopenic patients (ITP) and to decipher their possible clinical correlates. Eighty adults (≥ 18 years) were enrolled in the study; naive newly diagnosed 40 patients with primary ITP (according to the ASH 2019) and 40 sex and age-matched healthy controls, all groups are subjected for complete blood count (CBC), liver, and renal function tests, ESR, CRP, V-CAM, and VWF-Ag by enzyme-linked immunosorbent assay (ELISA). There was a highly statistically significant difference between case and control as regards to the mean level of VWF-Ag and V-CAM. vWF and V-CAM could serve as biomarkers for endothelial alterations and should be investigated as a predictor of thrombocytopenic bleeding and tailor patient management accordingly.

Post-translational polymodification of β1-tubulin regulates motor protein localization in platelet production and function

In specialized cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and coordinate unique morphologies and behaviors. The mechanisms by which b1-tubulin, the platelet and megakaryocyte (MK) lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational tubulin polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell derived MK, and healthy human donor platelets. We find distinct patterns of polymodification in MK and platelets, mediated by the antagonistic activities of the cell specific expression of tubulin tyrosine ligase like enzymes and cytosolic carboxypeptidase enzymes. The resulting microtubule patterning spatially regulates motor proteins to drive proplatelet formation in megakaryocytes, and the cytoskeletal reorganization required for thrombus formation. This work is the first to show a reversible system of polymodification by which different cell specific functions are achieved.

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

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

The Significance of Platelet-Albumin-Bilirubin (PALBI) Grade in Hepatocellular Carcinoma Patients Stratified According to Platelet Count.

BackgroundPlatelet–albumin–bilirubin (PALBI) has been demonstrated to be superior to conventional Child–Pugh (C-P) grade in evaluating liver function and prognosis of HCC patients. However, both thrombocytosis and thrombocytopenia are unfavorable for HCC survival. The aim of this study was to preliminarily investigate the prognostic value of PALBI in HCC patients with thrombocytopenia and excluding thrombocytopenia.MethodsIn this retrospective cohort study, we reviewed 465 cases of HCC patients who underwent radical surgery. PALBI grade was calculated based on preoperative serological examinations. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), which were assessed by Kaplan–Meier method and Cox regression. The prognostic performances of PALBI and other models were estimated by using the concordance index (C-index).ResultsDuring a median follow-up time of 28 months, 31.6% (147/465) of patients died and 33.5% (156/465) experienced recurrence. Multivariate analyses revealed that both thrombocytosis and thrombocytopenia were independently associated with poor OS and RFS compared with normal platelet count (PLT) in HCC patients. Stratified analysis further revealed that PALBI was a significant predictor for HCC survival in patients excluding thrombocytopenia but not in patients with thrombocytopenia. In particular, in HCC patients excluding thrombocytopenia, the combination of tumor size with PALBI (C-index = 0.730, 95% CI: 0.674–0.786) may be superior to the classical Barcelona Clinic Liver Cancer (BCLC) and Cancer of Liver Italian Program (CLIP) staging systems in predicting survival.ConclusionIn conclusion, PALBI grade, in particular the combination with tumor size, is an effective model for discriminating survival in HCC patients excluding thrombocytopenia but not in thrombocytopenic HCC patients.

Retrospective evaluation of lumbar puncture and intrathecal chemotherapy in thrombocytopenic patients

IntroductionLumbar puncture (LP) and intrathecal chemotherapy (IT CT) are common procedures and treatment options for hematologic patients. Although they can also be used in thrombocytopenic patients, there is no consensus on the safe cutoff value of platelet counts for LP and IT CT practices. AimThis research aimed to determine the safety of LP and IT CT administration in thrombocytopenic patients using different cutoff platelet values. MethodsOne hundred and fifty-two adult patients who had LP indications were evaluated. Among them, 42 patients received IT CT. The cerebrospinal fluid results from 100 procedures were available. ResultsThe preprocedural platelet count was <100.000/mm3 and <50.000/mm3 in 41 (41 %) and 18 (18 %) patients, respectively. Ten of these patients received platelet transfusion prior to LP. In the untransfused group, the platelet count was <50.000/mm3 in 12 (12 %) patients, among whom seven patients had a platelet count of <30.000/mm3. The traumatic tap was comparable among the transfused and untransfused groups (p = 0.632). No correlation was observed between the thrombocyte value and the traumatic tap (p = 0.891). The ratio of the traumatic tap was not significant between the patient groups with a platelet count of ≥50.000/mm3 or <50.000/mm3 (p = 0.418). After adding the transfused patients, the traumatic tap ratio remained nonsignificant between the two groups (p = 0.851). ConclusionHemorrhagic complications were rare in the thrombocytopenic patients who received IT CT after the LP procedure applied by experienced specialists. However, further prospective large studies evaluating the safety of procedures in thrombocytopenic patients are needed to make clear conclusion.

Fecal blood loss: A quantitative method of evaluating hemostasis in patients with thrombocytopenia.

The purpose of our studies was to determine if fecal blood loss can provide a quantitative measure of bleeding at platelet counts of 20 000/μL or less in patients with hypoproliferative thrombocytopenia and to document the effects of different prophylactic platelet transfusion triggers on fecal blood loss. Patients had an aliquot of their autologous red blood cells (RBCs) labeled with 51 Cr. Following reinjection of their radiolabeled RBCs, all feces and a daily blood sample were collected to determine fecal blood loss per day. Three different studies were performed in patients with thrombocytopenia: The first was in patients with thrombocytopenia with aplastic anemia who were not receiving platelet transfusions, and the other two trials involved thrombocytopenic patients with cancer who were receiving prophylactic platelet transfusions at platelet transfusion triggers of 5000/μL, 10 000/μL, or 20 000/μL. In patients with thrombocytopenia not receiving platelet transfusions, fecal blood loss does not increase substantially until platelet counts are 5000/μL or less. When platelet transfusions are given prophylactically to patients with cancer with chemotherapy-induced thrombocytopenia at platelet counts of 5000/μL or less, fecal blood loss and red cell transfusion requirements are the same as those for patients transfused prophylactically at higher transfusion triggers of 10 000 platelets/μL or 20 000 platelets/μL. However, the total number of platelet transfusions needed increases significantly, and the duration of the patient's thrombocytopenia tends to be longer at the higher platelet transfusion thresholds. A prophylactic platelet transfusion threshold of 5000/μL or greater is sufficient to maintain hemostasis in patients with thrombocytopenia.

Plasmacytoid Dendritic Cells Surveil Megakaryocyte Sialic Acid to Regulate Thrombopoiesis

The Thomsen-Friedenreich antigen (TF-antigen) occurs during exposure of the underlying Core-1 disaccharide (Gal-beta(1,3)GalNAc) through the loss of its capping sialic acid (Sia). Exposure of the cryptic TF-antigen occurs during inflammation, during acute infections with influenza viruses or bacteria, in malignancies, and is associated with thrombocytopenia. Exposure of the TF-antigen on circulating blood cells, including platelets and red blood cells (RBC), can lead to severe thrombocytopenia or hemolysis in hemolytic uremic syndrome and other immune diseases. Recent data suggest that altered Sia may cause platelet destruction because treatment with the sialidase inhibitor Tamiflu increases platelet count in healthy and thrombocytopenic patients. In humans, genetic mutations involving Sia synthesis and transport, and atypical cell surface sialylation, unrelated to any genetic mutation, are associated with reduced platelet count, supporting the role of Sia in regulating platelet count. Immune cells, including classical dendritic cells (cDCs), plasmacytoid dendritic cells (pDCs), and subsets of T cells (CD8+, CD4+, and Treg cells) can also affect immune thrombocytopenia pathogenesis. Like many other immune cells, cDCs, and pDCs express Siglecs (sialic-acid-binding immunoglobulin-like lectins), which often contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that act as immunosuppressors. Whether BM immune cells monitor MKs via glycan-lectin receptors, including Siglecs and Sia interactions, to control platelet production is unclear. To investigate the role of the TF-antigen in thrombopoiesis, we generated St3gal1MK-KO mice (Pf4-Cre) that display increased TF-antigen specifically in megakaryocytes (MK) and platelets. St3gal1MK-KO mice developed significant thrombocytopenia, but had normal platelet half-life, suggesting that the TF-antigen affected BM thrombopoiesis. In vitro MK maturation and proplatelet production from primary ST3Gal1MK-KO mouse BM cells were also normal, pointing to extrinsic factors in the BM environment affecting thrombopoiesis. Platelet counts of St3gal1MK-KO mice were restored to wild-type levels by 1) crossing St3gal1MK-KO mice with Jak3KO mice that have impaired of lymphoid cell development, 2) by treatment with anti-inflammatory dexamethasone, and 3) treatment with a depleting anti-CD4 antibody. Immunofluorescence staining of the St3gal1MK-KO BM revealed proplatelet structures positive for GPIba+ and the TF-antigen, being infiltrated by mononuclear cells resembling lymphocytes. We speculated that immune cells surveil megakaryocytes to control thrombopoiesis. Bulk RNAseq of CD4+ cells in St3gal1MK-KO BM confirmed a population bias for Type I interferon (IFN-I)-releasing pDCs, a cell type regulated by unique sialic acid binding lectins (Siglecs). Inhibition of IFN-I activity, by a blocking receptor antibody improved platelet counts in St3gal1MK-KO mice. Co-cultures of pDCs with MKs show inhibited pro-platelet formation when TF-antigen is present on MKs with elevated IFN-I levels. Gene set enrichment analysis of BM pDCs single cell RNASeq (scRNAseq) data further confirmed that TF-antigen exposure by MKs up-regulates IFN-I transcripts. scRNAseq also reveals a new population of immune cells with pDC transcript signature and concomitant upregulation of immunoglobulin re-arrangement gene transcripts Igkc and Ighm. In conclusion, the data shows that recognition of aberrant MK sialylation by pDCs regulates thrombopoiesis through IFN-I secretion. Disclosures No relevant conflicts of interest to declare.

Momelotinib's Spleen, Symptom and Anemia Efficacy Is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia

Momelotinib's Spleen, Symptom and Anemia Efficacy Is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia

A Pilot Study to Evaluate the Feasibility of Anti-Fibrinolytic Agents in Reducing Hemorrhagic Complications in Pediatric Patients with Thrombocytopenia

Background: The risk of bleeding remains high in thrombocytopenic pediatric hematology-oncology patients despite the use of prophylactic platelet transfusions. In one study, WHO grade 2 or higher bleeding occurred in &amp;gt;80% of pediatric subjects receiving hematopoietic stem cell transplantation or chemotherapy despite a platelet transfusion threshold of 10,000/µl. The risk of bleeding is not decreased with higher transfusion thresholds or increased platelet doses. Bleeding episodes are associated with increased mortality rates, greater utilization of resources and increased transfusion requirements. We examined the use of anti-fibrinolytic agents in decreasing bleeding events and platelet transfusions. Methods: We conducted a randomized double-blinded Phase 2 trial of tranexamic acid versus placebo in inpatient pediatric patients undergoing chemotherapy or HSCT expected to have prolonged thrombocytopenia. All patients admitted to the Oncology or HSCT services were screened for eligibility. Patients consenting for enrollment received either tranexamic acid 10m/kg/dose or normal saline every 8 hours while the platelet count as &amp;lt;30,000/ul until discharge or spontaneous platelet recovery (maximum 30 days). We conducted daily hemostatic assessments using the WHO bleeding scale and monitored adverse events and platelet transfusion requirements. Follow-up assessments took place at 7 and 30 days following completion of study medication. Primary aims were to assess safety and feasibility of tranexamic acid in children with hypoproliferative thrombocytopenia. Results: We screened 697 admissions over 11 months, 31 patients were eligible for enrollment. Enrollment was suspended in March 2020 for COVID reasons though screening continued through July 2020. An additional 10 eligible patients were identified in this period. The most common reasons for ineligibility included recent asparaginase administration, predicted inpatient stay &amp;lt;5 days and age ≤ 2 or ≥ 18 years. Eleven patients enrolled and completed all study procedures. There were no missed doses of medication, 88.4% of doses were administered within one hour of prescribed time. Patients remained on study for a mean of 11.1 days. Five patients each met criteria for spontaneous platelet count recovery or discharge, 1 patient received the study medication for 30 days. Bleeding (all grades) occurred on 29.5% of days. Grade 2 or higher bleeding occurred on 4.9% of days and was experienced by 27.3% of patients. The most common sites of bleeding were oral/nasal and cutaneous. Subjects received a median of 2 platelet transfusions per patient. There were no thromboembolic events or serious adverse events. Conclusion: Tranexamic acid is well tolerated can be safely administered to pediatric oncology patients as an adjunct to therapy. We are planning a multi-center randomized controlled trial to assess the efficacy of tranexamic acid in reducing bleeding complications in this population. Disclosures Triulzi: Fresenius Kabi: Consultancy; Cerus Corp: Research Funding. OffLabel Disclosure: Tranexamic Acid - This medication is being studied as an adjuvant to therapy to prevent bleeding complications and reduce platelet transfusions in pediatric patients with hypoproliferative thrombocytopenia.

Effects of Tranexamic Acid Prophylaxis on Bleeding Outcomes in Hematologic Malignancy: The a-TREAT Trial

Background: Despite optimal prophylactic platelet (plt) transfusion therapy for severe thrombocytopenia in patients undergoing treatment for hematologic malignancy, WHO Grade 2 or greater bleeding continues to occur at rates of 43% to 70%. Although antifibrinolytic therapy has been shown to reduce bleeding and transfusion needs in patients with inherited bleeding disorders and in multiple surgical settings, evidence in therapy-induced thrombocytopenia in hematologic malignancy is lacking. The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT) evaluated the effects of prophylactic TXA as an adjunct to routine transfusion therapy on bleeding and transfusion requirements in a multicenter, double blind placebo controlled randomized clinical trial in patients undergoing treatment for hematologic malignancy. Methods: Adult patients at 3 US academic medical centers with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) anticipated to have hypoproliferative thrombocytopenia were enrolled between June 15, 2016 and February 4, 2020. Randomization was stratified by site and therapeutic group: Chemotherapy, Allogeneic transplant, or Autologous transplant. Patients received study drug intravenously (1,000mg TXA or saline) or orally (1300mg TXA or placebo) every 8 hours beginning when the plt count was ≤30,000/µL and continued until platelet count recovery &amp;gt;30,000/ul or if a diagnosis of thrombosis was made. Patients were transfused prophylactically for counts of ≤10,000/µL or if indicated in the judgement of the treating physician. Daily assessments for bleeding were made by trained research staff (inpatients) or by self-assessment in a patient diary (outpatients), and by patient interview and chart review. The primary endpoint was the proportion of patients with bleeding of WHO grade 2 or above over 30 days after activation of study drug. A score test based on logistic regression was used, adjusted for study site and therapeutic group and adjusted for sequential monitoring. Multiple imputations were used to account for missing data. Secondary endpoints were number of transfusions and number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug. Results: 3,788 patients were screened and 360 patients consented. 330 patients were activated and evaluable; 327 received at least one dose of study drug. The adjusted odds ratio of grade 2+ bleeding was 0.86 (95% CI: 0.52, 1.38; p-value=0.74). The difference in mean number of transfusions was 0.1 (95% CI: -1.9, 2.0; p-value=0.94), while the average difference in days alive without grade 2+ bleeding was 0.1 (95% CI: -1.4, 1.5; p-value=0.94). No differences in exploratory outcomes were observed. The mean difference in transfusions per thrombocytopenic day was -0.02 (95% CI: -0.09, 0.04; p-value=0.51). The mean difference in RBC transfusions per thrombocytopenic day was 0.03 (95% CI: -0.05, 0.11; p-value=0.43). The average number of days with thrombocytopenia or bleeding was similar across treatment arms (9.2 [SD=6.7] TXA vs. 9.1 [6.2] placebo). The hazard ratio of time to grade 2+ bleeding or death was 0.96 (95% CI: 0.43, 2.16; p-value=0.92). The mean difference in highest grade of bleeding was -0.1 (95% CI: -0.2, 0.1; p-value=0.42). There were no deaths due to bleeding. VOD was observed in 3/164 TXA subjects (1.8%) and 2/163 (1.2%) placebo subjects. An increase in the incidence of central venous line occlusions and the use of tissue plasminogen activator was noted in the TXA arm. (11.0% vs. 19.5% and 25.8% vs. 42.1% for placebo and TXA groups, respectively). Recurrent line occlusion led to permanent discontinuation of drug in 4.9% of TXA and 1.8% of placebo subjects. No increase in any other non-catheter thrombotic events was noted. No patient died from a thrombotic event in 120 days following activation of study drug. Conclusions: Prophylactic TXA has no effect on the incidence of WHO Grade 2+ bleeding when given in addition to routine plt transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancy. An increased incidence of line occlusion in the TXA arm was observed but no increase in other types of thrombotic events was detected. Disclosures Gernsheimer: Rigel Corporation: Consultancy, Research Funding; Principia: Research Funding; Sanofi: Consultancy; Vertex: Consultancy; Dova Pharmaceuticals: Consultancy; Cellphire: Consultancy; Novartis: Consultancy; Amgen Corporation: Consultancy, Honoraria. Triulzi:Cerus Corp: Research Funding; Fresenius Kabi: Consultancy. Key:Uniqure: Consultancy; Takeda: Research Funding; Novo Nordisk: Other: Chair of Grants Committee; Grifols: Research Funding. OffLabel Disclosure: Tranexamic Acid is an antifibrinolytic agent approved for treatment of bleeding in patients with hemophilia to reduce the risk of hemorrhage during and following tooth extraction. The oral form is indicated for the treatment of cyclic heavy menstrual bleeding.

Assessing the yield and safety of endoscopy in acute graft-vs-host disease after hematopoietic stem cell transplant.

BACKGROUNDAcute gastrointestinal (GI) graft-vs-host disease (aGVHD) is the most complication of hematopoietic stem cell transplant (HSCT) in patients with hematologic malignancy. Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms. Further, the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIMTo understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODSWe analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy. The yield, sensitivity, and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy, various GI tract locations, and presenting symptoms.RESULTSCombined esophagogastroduodenoscopy (EGD) and flexible sigmoidoscopy (FS) demonstrated a greater diagnostic yield for aGVHD (83.1%) compared to EGD (66.7%) or FS (77.2%) alone with any presenting symptom. The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea (95.7% vs 99.1%) or nausea/vomiting (97.5% vs 96.8%). Normal-appearing mucosa was generally as specific (91.3%) as abnormal mucosa (58.7%-97.8%) for the presence of aGVHD. Adverse events such as bleeding (1.0%), infection (1.0%), and perforation (0.5%) only occurred in a small proportion of patients, with no significant differences in those with underlying thrombocytopenia (P = 1.000) and neutropenia (P = 0.425).CONCLUSIONCombined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.

Predicting 2-Day Mortality of Thrombocytopenic Patients Based on Clinical Laboratory Data Using Machine Learning.

Clinical laboratories have traditionally used a single critical value for thrombocytopenic events. This system, however, could lead to inaccuracies and inefficiencies, causing alarm fatigue and compromised patient safety. This study shows how machine learning (ML) models can provide auxiliary information for more accurate identification of critical thrombocytopenic patients when compared with the traditional notification system. A total of 50,505 patients' platelet count and other 26 additional laboratory datasets of each thrombocytopenic event were used to build prediction models. Conventional logistic regression and ML methods, including random forest (RF), artificial neural network, stochastic gradient descent (SGD), naive Bayes, support vector machine, and decision tree, were applied to build different models and evaluated. Models using logistic regression [area under the curve (AUC)=0.842], RF (AUC=0.859), artificial neural network (AUC=0.867), or SGD (AUC=0.826) achieved the desired average AUC>0.80. The highest positive predictive value was obtained by the SGD model in the testing data (72.2%), whereas overall, the RF model showed higher sensitivity and total positive predictions in both the training and testing data and outperformed other models. The positive 2-day mortality predictive rate of RF methods is as high as 46.1%-significantly higher than using the traditional notification system at only 14.8% [χ2(1)=81.66, P<0.001]. This study demonstrates a data-driven ML approach showing a significantly more accurate 2-day mortality prediction after a critical thrombocytopenic event, which can reinforce the accuracy of the traditional notification system.

Safety of bone marrow aspiration and biopsy in severely thrombocytopenic patients.

To assess the safety of fluoroscopically guided drill-assisted bone marrow aspirate and biopsy in severely thrombocytopenic patients. The study was approved by the IRB with waiver of informed consent. Retrospective review of 111 bone marrow aspirate and biopsies (BMAB) performed in 94 patients who received a CT scan which included the pelvis and biopsy site within the 7 days following the BMAB. The 94 patients were subdivided based on their platelet count: severe thrombocytopenia (< 20 platelets × 109/L), thrombocytopenia (20-50 platelets × 109/L), and control (> 50 platelets × 109/L). The procedure report was reviewed for sedation time, aspirate volume, and aggregate size of core biopsy specimens. The electronic medical record was reviewed for specimen adequacy; pathologic diagnosis; body mass index; pre- and post-procedure labs including platelet count, hemoglobin (HGB), hematocrit (HCT), prothrombin time (PT), and international normalized ratio (INR) levels; post-procedural transfusion; and complications including mortality at 30 and 90 days. CT scans were independently reviewed by 2 fellowship-trained radiologists for the presence of post-procedural hemorrhage. There was no significant difference in CT-identified post-procedural hematoma, or change in the hemoglobin and hematocrit levels pre- and post-procedure between the three groups. There was no significant difference in complication rate or all-cause mortality. There was a significant difference in transfusion at 30 days with thrombocytopenic and severely thrombocytopenic patients more likely to receive transfusion within the 30 days post-procedure. Fluoroscopically guided BMAB can be safely performed in patients with severe thrombocytopenia.

PARTIAL SPLENIC EMBOLIZATION AS A TREATMENT FOR INTRACRANIAL HEMORRHAGE CAUSED BY IMMUNE THROMBOCYTOPENIC PURPURA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune Thrombocytopenic Purpura (ITP) is a disease of immune mediated platelet destruction and decreased production. Autoimmune platelet destruction occurs in tissue macrophages, mainly in the spleen. Initial treatment for ITP includes steroids and, for patients who require quicker elevation of platelet count, intravenous immunoglobulin (IVIG). Second line treatments include rituximab and newer agents that work by thrombopoiesis stimulation. Splenectomy, also a second line treatment, is generally used only after all medical options have failed due to potential complications. We report a case of partial splenic embolization (PSE) in a patient with refractory ITP presenting with acute intracranial hemorrhage (ICH). CASE PRESENTATION: A 38-year-old male with refractory ITP, initially treated with steroids, IVIG, and maintenance eltrombopag, presented to an academic medical center with two days of headache followed by acute onset weakness and slurred speech the day of presentation. Platelet count was 6k/uL; computed tomography (CT) found a pontine hemorrhage measuring 1.8x1.9x1.7cm causing effacement of the right ambient and pre-pontine cistern. He was initially treated with 4mcg/kg romiplostim, 60g IVIG, 40mg dexamethasone, 4U platelets and intubated for airway protection. Repeat laboratory results showed platelet count of 3k/uL; repeat CT showed expanding hemorrhage with worsening mass effect. Due to his worsening condition, we administered recombinant factor VIIa and performed an emergent PSE using approximately 3 ml of 300-500 µm embospheres via a right common femoral artery approach. Within nine hours of PSE, his platelet count increased to 218k/uL. Repeat CT showed stable hemorrhage; MRI did not show an underlying cause for his bleed. His platelets continued to increase, neurologic status improved and he was extubated. When the patient’s platelet count dropped to 79k/uL 11 days post-embolization, he underwent laparoscopic splenectomy. DISCUSSION: Splenectomy used to treat ITP has a high long-term remission rate.2 While there have been small, retrospective studies in the use of PSE with promising results, we found no reports in which PSE was used in an adult with ICH. Due to this presentation’s emergent nature, an active ICH and risk of bleeding, we opted for PSE rather than splenectomy for both speed and a presumed lower immediate complication rate. The PSE stabilized the patient by stopping the ICH and raising platelet count, enabling the patient to undergo laparoscopic splenectomy at a later date. CONCLUSIONS: PSE can be a safe alternative or bridge to splenectomy in patients with acute bleed due to ITP. Reference #1: Kuwana M, et al. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost. 2009;7(2):322-329 Reference #2: Mikhael J, Northridge K, Lindquist K, Kessler C, Deuson R, Danese M. Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: a systematic review. Am J Hematol. 2009;84(11):743-748. DISCLOSURES: No relevant relationships by Lewis Eisen, source=Web Response No relevant relationships by Nader Emami, source=Web Response No relevant relationships by David Hirschl, source=Web Response No relevant relationships by David Schecter, source=Web Response

Platelet Function Analysis by Flowcytometry in Thrombocytopenic Trauma Patients

Hemostasis is dependent on sufficient quantity and quality of circulating functional platelets. Platelet function in trauma patients with thrombocytopenia and its impact on the clinical outcome is not adequately explored. Whether platelet dysfunction has a role in the pathogenesis of acute traumatic coagulopathy needs to be studied. Blood samples were collected from 70 thrombocytopenic trauma patients before transfusing platelets and assessed for platelet activation and platelet aggregation using flowcytometry. Primary outcome was in-hospital mortality. Platelet dysfunction was identified in 57.1% of thrombocytopenic trauma patients. A weak inverse correlation between percentage of activated platelets and APTT was observed (Spearman coefficient - 0.25, p = 0.03). A sensitivity and specificity of 66.6% was achieved for a cut off of ≤ 6.5% of platelet activation post trauma with ROC-AUC of 0.658 for identifying coagulopathy. No correlation with mortality however was observed (p > 0.05). Platelet dysfunction had a weak association with coagulopathy suggesting limited contribution of platelet dysfunction in pathogenesis of acute traumatic coagulopathy and warrants further research.

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

Inorganic polyphosphate (polyP) is a morphogenetically active and metabolic energy-delivering physiological polymer that is released from blood platelets. Here, we show that polyP efficiently inhibits the binding of the envelope spike (S)-protein of the coronavirus SARS-CoV-2, the causative agent of COVID-19, to its host cell receptor ACE2 (angiotensin-converting enzyme 2). To stabilize polyP against the polyP-degrading alkaline phosphatase, the soluble polymer was encapsulated in silica/polyP nanoparticles. Applying a binding assay, soluble Na-polyP (sizes of 40 Pi and of 3 Pi units) as well as silica-nanoparticle-associated polyP significantly inhibit the interaction of the S-protein with ACE2 at a concentration of 1 µg/mL, close to the level present in blood. This inhibition is attributed to an interaction of polyP with a basic amino acid stretch on the surface of the receptor binding domain of S-protein. PolyP retains its activity in a flushing solution, opening a new strategy for the prevention and treatment of SARS-CoV-2 infection in the oropharyngeal cavity. The data suggest that supplementation of polyP might contribute to a strengthening of the human innate immunity system in compromised, thrombocytopenic COVID-19 patients.

Bleeding outcomes in thrombocytopenic acute leukemic patients with venous thromboembolism.

Cancer‐associated thrombosis in acute leukemia patients with severe thrombocytopenia (platelets ≤50 × 109/L) poses a management challenge due to competing risks of bleeding and recurrent thrombosis. A retrospective analysis was conducted to determine the occurrence of clinically relevant bleeding (CRB) rates during treatment for acute venous thromboembolic events (VTE) in thrombocytopenic acute leukemic patients. A cohort of 74 patients were subgrouped into three VTE‐treatment interventions: anticoagulation (n = 24), inferior vena cava filter placement (n = 22), and observation (n = 28). Multivariate analysis found a significant correlation between CRB occurrence and quantity of overall blood transfusions, chemotherapy administration, and relapsed leukemia presentation. There was no difference in the occurrence of CRB between VTE‐treatment subgroups, regardless of initial platelet count at the time of VTE diagnosis. Regarding the hematologic parameters, only the velocity of the platelet count recovery was associated with the risk of bleeding. From this analysis, it appears the trajectory of the platelet count and the factors associated with a slower recovery of it, are the main determinants for the occurrence of hemorrhagic complications during VTE treatment in acute leukemia.

AML-035: Bleeding Outcomes in Thrombocytopenic Acute Leukemia Patients with Venous Thromboembolism at a Comprehensive Cancer Center

Context Cancer-associated thrombosis (CAT) in leukemia patients with severe thrombocytopenia poses a treatment challenge due to competing risks of bleeding and recurrent thrombosis resulting in a narrow therapeutic index for antithrombotic therapies. Objective To determine rates of clinically relevant bleeding (CRB) during management of acute venous thromboembolic event (VTE) in thrombocytopenic acute leukemia patients. Design Retrospective analysis using chart review. Patients Patients (n=74) with acute leukemia admitted to the University of Texas M.D. Anderson Cancer Center, January 2002 - March 2016. Included patients were older than 17 years, with proximal lower extremity deep venous thrombosis and/or pulmonary embolism, and thrombocytopenia (platelet levels ≤50×109/L) on at least two consecutive measures. Patients were sub-grouped into three VTE-treatment interventions: anticoagulation (32.4%), inferior vena cava filter (29.7%), and observation (37.8%). Main outcome measures Rates of CRB and by VTE-treatment intervention group. Association between CRB risk and clinical and laboratory characteristics by multivariate model based on backward model selection. Results Twenty-nine patients (39.2%) suffered CRB during the study (9 had clinically relevant non-major bleeding, 19 had major bleeding, and 1 had both major and non-major bleeding). Patients with relapsed leukemia bled more than those with de novo leukemia (P=0.0294). The use of anticoagulation did not increase the occurrence of CRB (P=0.6035). Use of chemotherapy increased the odds of bleeding by six times (P=0.043). Patients with CRB received more transfusions of platelets (P=0.0012), packed red blood cells (P=0.0017), and fresh frozen plasma (P=0.0573) compared to those who did not bleed. Baseline platelet count was not a significant factor associated to CRB(P=0.35), but the rate of increased platelet counts over time correlated with decreased bleeding chance (P=0.01). Conclusions There was a significant correlation between the occurrence of CRB and quantity of overall blood product transfusions, use of chemotherapy, and relapsed leukemia presentation. There was no difference in rates of CRB between VTE-treatment sub-groups, regardless of platelet count at time of VTE diagnosis. It appears the platelet count trajectory and the factors associated to a slower recovery of it are the main determinants for hemorrhagic complications during VTE treatment in acute leukemia.

Lumbar Neuraxial Procedures in Thrombocytopenic Patients Across Populations: A Systematic Review and Meta-analysis

(J Clin Anesth. 2020;61:109666) Presently, there is no agreement among experts in regards to the safe minimum threshold platelet count for lumbar neuraxial anesthetic procedures, as there are limited data available on neuraxial anesthetic procedures performed on thrombocytopenic patients. During cesarean deliveries, there are important maternal and fetal factors and side effects to consider when choosing to administer general anesthesia rather than neuraxial anesthesia. Because more data on spinal epidural hematoma are needed, Bauer and colleagues conducted this systematic review to assemble reported lumbar neuraxial procedures (lumbar puncture; spinal, epidural, or combined spinal-epidural analgesia/anesthesia; epidural catheter removal) from various thrombocytopenic populations to bring some clarity to the risk of spinal epidural hematoma.