About

Caitlin O'Neill is an Assistant Professor of Clinical Medicine at the Keck School of Medicine of USC. She has been recognized as a Broad Clinical Research Fellow at the Keck School of Medicine of USC from 2020 to 2022. Her research and clinical interests include hematology, with a focus on diagnostic and management challenges related to erythrocytosis, systemic mastocytosis, Helicobacter pylori infection in immune thrombocytopenia, myelofibrosis, and early myelofibrosis treatment. Her work involves exploring emerging areas in these fields, contributing to the understanding and treatment of complex hematological conditions.

Selected publications

• Relationship between cortical electrical responsiveness and changes in regional cerebral oxygenation (rSO2) and return of spontaneous circulation in prolonged cardiac arrest: a multi-center observational study

  Resuscitation · 2026-02-25

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• A phase 2, open-label study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of DISC-3405 in participants with polycythemia vera (PV)

  Blood · 2025-11-03

  articleOpen access

  Abstract Background and Significance: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with pathologic erythrocytosis, most often driven by somatic mutations in the JAK2 gene. A key treatment goal is maintaining hematocrit (HCT) below 45% to reduce thromboembolic complications. Current standard of care for patients diagnosed with PV, including phlebotomy (PHL) and cytoreductive therapies (CRT), can be burdensome, may lead to intolerable adverse effects, and often are associated with symptoms of iron deficiency. DISC-3405 is an investigational, novel, humanized immunoglobulin (Ig)G1 monoclonal antibody that targets transmembrane serine protease 6 (TMPRSS6, also known as matriptase 2) to stimulate endogenous production of hepcidin, a peptide hormone secreted by hepatocytes and the key regulator of iron homeostasis. In a randomized, placebo-controlled study in healthy volunteers (DISC-3405-101), DISC-3405 administered subcutaneously at doses between 37.5-300 mg was well-tolerated, resulted in dose-dependent pharmacokinetic (PK) profiles, significantly increased hepcidin production with corresponding reductions in serum iron levels, and reduced HCT (Liu et al, EHA 2025, PS2207). DISC-3405 is being developed as a potential treatment for patients with PV requiring HCT reduction, regardless of baseline risk or concurrent CRT. Study Design and Methods: This is a multi-center, open-label, 52-week Phase 2 study enrolling up to 20 patients with PV in the United States to assess the safety, tolerability, PK, pharmacodynamics (PD), and therapeutic effect of DISC-3405 on PV disease control as evidenced by HCT reduction and PHL requirements. After an observation period of 4-12 weeks, participants will be treated and followed for 52 weeks and dosed up to 300 mg every 2 weeks. After 52 weeks, participants can continue in an optional 2-year continuation phase where long-term safety and efficacy will continue to be assessed. The main efficacy endpoints of the study include the proportion of participants achieving therapeutic response, defined as absence of PHL eligibility; number of PHLs during the treatment period; and proportion of participants with HCT values <45% throughout the study. PHL eligibility is defined as (1) HCT ≥45% and ≥3% (absolute change) of pre-treatment values or (2) HCT >48%. Eligible participants include adults 18 or older who meet the 2022 World Health Organization diagnostic criteria for PV. Clinically acceptable laboratory values include HCT <45% prior to Day 1 (dosing) or HCT <48% if followed by a PHL within 2 weeks prior to first dose of study drug, white blood cells 4000/μL to 20,000/μL (inclusive), and platelets 100,000/μL to 1,000,000/μL (inclusive). Participants should have at least 3 PHL in 26 weeks or 5 PHL in the 52 weeks prior to screening, and at least 1 PHL within 12 weeks prior to screening. Participants receiving CRT must have been on the therapy for at least 6 months and on a stable PV treatment regimen, including hydroxyurea, interferon, or ruxolitinib, for at least 2 months. Participants treated with only PHL must have stopped CRT 6 months before screening. Key exclusion criteria include participants that require PHL at HCT levels <45%, clinically significant thrombosis within 2 months prior to study treatment, active or chronic bleeding, estimated glomerular filtration rate of <30 mL/min/1.73 m2, and history of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable in discussion with the Sponsor. The study will enroll participants from approximately 15-20 sites in the United States. Additional details can be found at https://clinicaltrials.gov/study/NCT06985147.

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• Evaluation of the novel TMPRSS6 antisense inhibitor sapablursen for treatment of polycythemia vera: Results of the imprssion clinical trial

  Blood · 2025-11-03

  article

  Abstract Background: Polycythemia vera (PV) is characterized by excessive erythrocytosis and elevated hematocrit (Hct), which is associated with increased risk of thrombotic events. Controlling Hct levels (<45%) is a key therapeutic goal to reduce thrombotic events. Sapablursen (ISIS 702843) is a liver-directed, ligand-conjugated antisense oligonucleotide that suppresses transmembrane serine protease 6 (TMPRSS6) to enhance hepcidin production thereby restricting iron availability and reduced erythrocytosis. We are reporting the topline results of the IMPRSSION study (NCT05143957), an ongoing global, open-label phase 2 trial evaluating the safety and efficacy of sapablursen for Hct control and reducing phlebotomy rate in patients with PV. Methods: Eligible patients met 2016 WHO diagnostic criteria for PV, were required to have >3 phlebotomies within six months prior to screening, including >1 phlebotomy in the last 12 weeks. There were no exclusions for HCT prior to randomization. Patients received monthly subcutaneous doses of sapablursen in Cohort A (high dose) or Cohort B (low dose), during a 37-week treatment period. The primary efficacy endpoint was the reduction in the frequency of phlebotomy during the last 20 weeks of the treatment period (Week 17-37) compared to baseline (defined as the mean weekly phlebotomy rate during the six months prior to screening through the first dose of sapablursen). Phlebotomy was performed when Hct levels were ≥45% or at the investigator's discretion, confirmation of Hct was not required for phlebotomy. Serial assessments of serum hepcidin, TSAT and ferritin were conducted. The 10-item Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF-TSS) assessed the change in symptoms from baseline to Week 37. Results: Forty-nine (49) patients received at least one dose of sapablursen (full analysis set) in either Cohort A (n=32) or Cohort B (n=17). The median age was 61 years, 40 (82%) were male, and 29 (59%) classified as high risk. The primary endpoint was met at both dose levels. The weekly phlebotomy rate (mean±SD) decreased from baseline of 0.15±0.07 (~7.8/yr) to 0.05±0.09 (~2.6/yr) during the primary endpoint window (Week 17-37) in Cohort A (n=32, p<0.0001; 95%CI, -0.13, -0.07), and from 0.17±0.07 (~8.9/yr) to 0.07±0.07 (~3.6/yr) in Cohort B (n=17, p=0.0001; 95%CI, -0.14, -0.06). The mean MPN-SAF-TSS was reduced at Week 37 by 32% in Cohort A (change from baseline LSM -6.2, p=0.005) and 11% in Cohort B (change from baseline LSM -2.7, p=0.344). The proportion of patients with Hct control (<45%) without phlebotomy from week 17 to 37 in Cohort A and B was 53% (17/32) and 35% (6/17), respectively. Serum hepcidin was increased from baseline values of 0.25±0.6 to 5.05±4.7 nM at Week 13 in Cohort A (p<0.0001) and from 0.68±1.7 to 2.06±3.6 nM in Cohort B (p=0.0142). A sustained low TSAT was observed between Weeks 17-37 (6.0±2.1% and 5.5±2.0% in Cohort A and 8.9±5.0% and 7.0±3.4% in Cohort B). Serum ferritin increased over time from 18±22 ng/mL and 28±58 ng/mL at baseline in Cohort A and B, respectively, to 44±47 ng/mL and 41±85 ng/mL at Week 37, respectively. Sapablursen was generally safe and well-tolerated. The incidence of injection site reactions was 12.2% (6/49). Injection site reactions did not recur following multiple injections, were not progressive and resolved spontaneously. There was one death on study due to transformation to AML which was deemed as not related to the study drug. Conclusions: Treatment of PV patients with sapablursen increased serum hepcidin, controlled Hct, reduced phlebotomy need and improved quality of life in a dose-dependent manner. These findings highlight the potential of sapablursen as a therapeutic approach in PV and support further development.

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• Characterizing Thrombotic Risk in TEMPI Syndrome: A Retrospective Case Series

  Blood · 2024-11-05

  articleSenior author

  Introduction: TEMPI Syndrome was first described in 2011 as a rare syndrome that typically presents with five core clinical characteristics specified by its acronym: telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Since its first description, cases have been reported with additional clinical features including other cutaneous findings, serous cavity effusions, and vascular events, including thrombosis and hemorrhage. The suggested diagnostic criteria include three major criteria that appear in all patients with TEMPI syndrome (telangiectasias, elevated erythropoietin (EPO) level and erythrocytosis, and monoclonal gammopathy) and two minor criteria that are not always present (perinephric fluid collections and intrapulmonary shunting). The possibility of an “other criterion” of venous thromboembolism (VTE) has been suggested, but there has been limited research to understand its true incidence. Several characteristics of TEMPI Syndrome are associated with VTE in other clinical contexts. There is an increased risk of VTE in disorders of erythrocytosis such as Polycythemia Vera, Chuvash Polycythemia, secondary erythrocytosis, and idiopathic erythrocytosis. In addition, monoclonal gammopathy (MG), both of undetermined significance (MGUS) and of clinical significance (MGCS), has a statistically significant association with VTE. Methods: To understand the incidence of VTE in TEMPI Syndrome, we reviewed the literature for all published cases of TEMPI Syndrome. The authors of each publication were contacted to provide clinical data including age, sex, TEMPI characteristics, type and timing of thrombosis if present, treatment of TEMPI, and whether the patient was undergoing phlebotomy. Results: We identified 42 patients with TEMPI Syndrome reported in the literature. Detailed clinical data on VTE was obtained for 14 patients. The three major clinical criteria were present in all 14 patients. Of the 14 patients, nine experienced at least one VTE event. For the 9 patients with VTE, the median age was 53 (36-67) and 56% were female. For the 5 patients without VTE, the median age was 56 (range 40-75) and 60% were female. Most patients had IgG Kappa MG which is the most common form of MG found in TEMPI Syndrome. However, one patient with VTE and two patients without VTE had IgA Lambda MG, while another patient with VTE had IgM Lambda MG. EPO levels varied; patients with VTE had EPO levels from 73.5 to >5000 mU/mL and patients without VTE had levels from 433 to 5728 mu/mL. The hematocrit ranged from 55-64% in patients with VTE and 51-59% in patients without VTE. Of the patients with VTE, the type included lower extremity DVT + pulmonary embolism (PE) (2), jugular venous thrombosis (2), upper extremity DVT alone (1), lower extremity DVT alone (1), cerebral venous sinus thrombosis (2), Superior Vena Cava thrombus (1), and cardiac apex thrombus (1). There were no arterial clotting events in any of the 14 patients. Conclusion: The prevalence of VTE in patients with TEMPI Syndrome is high, with at least 21.4% of known patients developing VTE during their clinical course. VTE in TEMPI Syndrome can occur as a PE, DVT, or atypical site thrombosis, but the small sample size limits analysis of specific risk factors. Details on thrombotic events are lacking in the literature and further attempts to obtain these data are underway. Clinicians should be aware of the risk of VTE in patients with TEMPI, particularly in unusual locations, and further research on the impact of treatments such as phlebotomy and myeloma-directed therapies is underway to distinguish pathophysiology

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• Idiopathic erythrocytosis: A diagnostic and management challenge with emerging areas for exploration

  British Journal of Haematology · 2024-01-23 · 2 citations

  review1st author

  Despite published algorithms for approaching the work-up of erythrocytosis, a significant proportion of patients are left with uncertainty as to its aetiology and prognosis. The term 'idiopathic erythrocytosis' (IE) is applied when known primary and secondary aetiologies have been ruled out. However, the assignment of secondary aetiologies is not always straightforward or evidence based, which can lead to misdiagnosis and heterogeneity in cohort studies. Furthermore, new studies have identified germline or somatic mutations that may affect prognosis. Epidemiological and cohort data are inconsistent as to whether IE increases the risk for complications such as arterial and venous thromboembolism, clonal transformation or comorbid conditions. Randomized trials assessing the role of phlebotomy for long-term management of IE have not been performed, so treatment remains a vexing problem for clinicians. Standardization of terminology and testing strategies, including comprehensive genetic screening in clinical research, are key to refining our understanding of IE.

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• Clinical and pathological features of clonal cytopenia of undetermined significance presenting with isolated thrombocytopenia (<scp>CCUS‐IT</scp>)

  European Journal Of Haematology · 2023-12-13

  articleOpen access1st authorCorresponding

  Abstract Background Clonal cytopenia of undetermined significance (CCUS) is defined as somatic mutations of myeloid malignancy‐associated genes in the blood or bone marrow with one or more persistent unexplained cytopenias that do not meet diagnostic criteria for a defined myeloid neoplasm. CCUS with isolated thrombocytopenia (CCUS‐IT) is rare. Methods This is a retrospective case series of patients with prolonged isolated thrombocytopenia, a pathogenic mutation on a myeloid molecular panel, and a bone marrow biopsy with morphologic atypia below the WHO‐defined diagnostic threshold for dysplasia. Results Five male patients were identified with a median age at CCUS‐IT diagnosis of 61 years (56–74). Median duration of thrombocytopenia prior to CCUS‐IT diagnosis was 4 years (3–12), and median platelet count at CCUS‐IT diagnosis was 41 × 10 3 /μL (26–80). All patients had megakaryocytic hyperplasia and megakaryocytes with hyperchromasia and high nuclear‐cytoplasmic ratio. Pathogenic SRSF2 mutations were identified in all 5 patients with median variant allele frequency of 36% (28%–50%). Three patients were treated with IVIg and/or steroids with no response; one of three responded to thrombopoietin receptor agonists. Three patients progressed to MDS and one to AML. Discussion We describe the clinicopathological features of CCUS‐IT which can mimic immune thrombocytopenia.

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• AWAreness during REsuscitation - II: A multi-center study of consciousness and awareness in cardiac arrest

  Resuscitation · 2023-07-07 · 59 citations

  articleOpen access
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• Clinicopathological Features of Isolated Thrombocytopenia Associated with <i>SRSF2</i> Mutations: A Case Series

  Blood · 2022-11-15

  articleSenior author

  Introduction: Mutations of SRSF2, a gene involved in RNA splicing, are identified across a heterogenous group of myeloid neoplasms including MDS, CMML, and MPN. SRSF2 mutations have been associated with thrombocytopenia in MDS, but not in the case of MDS/MPN overlap conditions. When co-mutated with TET2, SRSF2 is associated with monocytosis and a myeloproliferative phenotype. SRSF2 mutations are also identified in normal individuals and in those with clonal cytopenias of undetermined significance (CCUS). Studies have examined genotype-phenotype correlations in myeloid malignancies, but similar analysis of the heterogeneity amongst patients with CCUS are lacking. Although dysplasia is not a defining feature of CCUS, sub-diagnostic dysplasia can be seen in CCUS and this subset notably had a higher proportion of spliceosome mutations. Here we describe the clinical and pathological features of a series of CCUS patients with prolonged, isolated thrombocytopenia and a SRSF2 mutation. Methods: We conducted a retrospective review of the electronic medical records of patients seen in the outpatient Hematology Clinic at the University of Southern California Norris Comprehensive Center between May 2014 and December 2021. Patients with persistent (> 6 months) isolated thrombocytopenia, a SRSF2 pathogenic mutation identified on a myeloid molecular panel, and absence of WHO-defined dysplasia or hematologic neoplasm on initial bone marrow biopsy were included. A work-up for alternative etiologies of thrombocytopenia was completed based on the clinical judgment of the treating physician. Bone marrow biopsies were reviewed by 2 independent hematopathologists. This study was approved by the Institutional Review Board of the University of Southern California. All patients signed informed consent. Results: Five patients met criteria for inclusion. All patients were male. Median age at diagnosis of thrombocytopenia was 61 years (56-74). Two patients were Asian and 3 were Caucasian. The median time from diagnosis of thrombocytopenia to the identification of a mutation on a myeloid molecular panel was 4 years (3-12). No patients had a family history of hematologic malignancy. Initial bone marrow biopsies did not meet WHO-defined thresholds for morphologic dysplasia. However, all patients had megakaryocytic hyperplasia and megakaryocytes with hyperchromasia and high nuclear-cytoplasmic ratio in 20% of megakaryocytes (Figure 1). Two patients who had CD34 staining showed positive staining in 30% of megakaryocytes. Four patients had normal cytogenetics and 1 patient had monosomy 7. Median bone marrow cellularity was 65% (30-80%). Two patients had intermittent peripheral monocytosis but did not meet the diagnostic criteria for CMML. No monocyte proliferation or immature monocytes were seen on bone marrow. SRSF2 mutations were P95H in 3 patients and P95L in 2 patients. Average variant allele frequency was 37.3% (range 28 - 50.2). Four patients had a co-occurring TET2 mutation; other co-mutated genes included RUNX1 (3 pts.), ASXL1 (1 pt.), DNMT3A (1 pt.), and NF1 (1 pt.). Median number of co-occurring mutations was 2 (0-3). Three patients were treated empirically for immune thrombocytopenia and had no response to IVIG and/or steroids. Three patients were treated with thrombopoietin receptor agonists (2 eltrombopag, 1 romiplostim) and had minimal transient platelet count increases not meeting the IWG MDS criteria for response. One patient was treated with hypomethylating agents for 4 months before progressing to MDS or AML. Four patients required as-needed platelet transfusions. To date, 4 have progressed to MDS or AML with a median time from diagnosis to progression of 6.3 years (range 5-10). Three patients have received allogeneic hematopoietic stem cell transplant. Conclusion: This series describes a subset of CCUS patients with isolated thrombocytopenia associated with SRSF2 mutations. We also describe atypical megakaryocytic findings which do not meet current WHO diagnostic criteria for dysmegakaryopoiesis; however, the uniform presence of these findings in this cohort suggests an association with thrombocytopenia and CCUS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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• A Pilot/Safety Study of sEphB4-Hsa in Combination with a Hypomethylating Agent for Patients with Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia Previously Treated with a Hypomethylating Agent

  Blood · 2020-11-04

  article1st authorCorresponding

  Background: Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm that results in bone marrow failure and frequently leads to acute myeloid leukemia (AML). Hypomethylating agents (HMA) are the only FDA-approved treatment for MDS and among few options for chemotherapy-ineligible patients with AML. There are limited options for patients in whom HMA therapy fails and who are not candidates for allogeneic stem cell transplant, so therapies that complement or restore sensitivity to HMAs are needed. Studies have shown increases in bone marrow microvessel density (MVD) and angiogenic markers in patients with MDS and AML. A decrease in MVD has been shown to correlate with response to hypomethylating agents in MDS. A receptor-ligand interaction, comprised of receptor EphB4 and membrane localized ligand EphrinB2, mediates angiogenesis in normal tissue and appears to be a target unique to many cancer types. We have previously shown EphB4 to be highly expressed and a driver of leukemic cell survival in a subset of AML patients. Our group has developed a human fusion protein, sEphB4-HSA, that blocks bidirectional signaling induced by EphB4-EphrinB2 interaction to inhibit tumor cell proliferation and angiogenesis. In phase I clinical trials of sEphB4-HSA in various tumor types, there were no myelosuppressive effects and minimal toxicity. Given its safety in phase I and potential to inhibit leukemic cell proliferation and angiogenesis, we proposed a pilot trial to evaluate the safety of sEphB4-HSA in combination with HMAs in MDS and AML patients who have failed treatment with HMAs. Methods: This pilot study was designed to enroll 6 patients with relapsed/refractory intermediate or high-risk MDS and 6 patients with AML refractory to or relapsed to HMA treatment and who are deemed unfit for chemotherapy. Treatment consisted of sEphB4-HSA 15 mg/kg IV every 2 weeks in combination with the FDA-approved HMA most recently or currently being used for treatment (decitabine 20mg/m2 IV/1hr on days 1 to 5 every 28 days or azacitidine 75mg/m2 SC or IV on days 1 to 7 every 28 days). Patients were treated for as long as they were receiving clinical benefit up to 12 months. The primary endpoint was toxicity and tolerability of sEphB4-HSA in combination with HMA. Toxicity was assessed and graded after each cycle according to the CTCAE version 4. Tolerability was defined as the ability to complete two cycles of treatment without the occurrence of dose-limiting toxicity. A secondary efficacy endpoint was to assess best overall response, based on the IWG Working Group Criteria for MDS and AML, during the first two cycles of treatment. Enrollment was stopped after 7 patients due to expiration of funding. Results: Three patients with intermediate-risk MDS were treated for a median duration of 6 cycles (2-12) and 4 patients with AML were treated for 2 cycles. Median age was 75.5 years (67.9-84.8) and 57.1% were male. HMA included azacitadine in 6 patients and decitabine in one patient. There were no dose-limiting toxicities. There were 8 grade 3/4 events attributed to HMA, which included: neutropenia (2), thrombocytopenia (3), and leukopenia (3). There were 3 grade 3/4 events attributed to sEphB4, which included: febrile neutropenia (1), leukopenia (1), and hypertension (1). Of the MDS patients, 2 had stable disease, 1 patient after 2 cycles and 1 patient after 4 cycles. One patient achieved a hematologic improvement-erythroid after 6 cycles. AML patients had no disease response. Reasons for treatment discontinuation were death (1), disease progression (2), patient's decision (1), physician's decision (2), and hospice (1). Notably, a comparison of bone marrow biopsies at baseline and after 8 weeks of treatment demonstrated a decrease in MVD (Figure 1). Discussion: This pilot study found sEphB4 in combination with HMAs to be tolerable with no significant toxicity beyond that expected with HMA therapy and associated with potential clinical benefit in MDS patients. Improvement in abnormal bone marrow MVD may indicate a potential for sEphB4-HSA plus HMA therapy to alter the malignant microenvironment in MDS/AML. Disclosures No relevant conflicts of interest to declare.

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• The Role of D-Dimer for Optimal Thromboprophylaxis Strategy in Patients with COVID-19

  Blood · 2020-11-04

  articleOpen access

  Background: Novel coronavirus infection (SARS CoV-2 or COVID-19) is associated with a high risk of thrombotic complications, including macro- and micro-thrombi in major organs, leading to increased morbidity and mortality. Anticoagulant use, mainly heparin, which has both anticoagulant and anti-inflammatory properties, has been suggested as potentially beneficial. However, the optimal dose of anticoagulant for patients with COVID-19 is unknown. Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19. Methods: This single-center retrospective cohort study is part of an ongoing Quality Improvement project on the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option, being conducted at our medical center. Data on the type, dose, and indication for anticoagulation as well as outcomes including thrombosis, bleeding and survival was collected for inpatients diagnosed with COVID-19 between mid-March and June 15, 2020. To address COVID-coagulopathy we developed a d-dimer-based anticoagulation protocol for patients with COVID-19 (Figure 1). We recorded anticoagulant use as either standard prophylactic, escalated prophylactic (low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units or enoxaparin 0.5mg/kg subcutaneously every 12 hours) or standard therapeutic dose used during the hospitalization. The primary endpoints assessed were ISTH-defined major and clinically relevant non-major bleeding (CRNMB) events and survival. Secondary endpoints included incidence of breakthrough thrombosis and duration of hospitalization. Results: A total of 263 patients with COVID-19 were reviewed. Of these, 68.44% of patients received prophylactic, 12.55% escalated prophylactic and 19.01% therapeutic dosage. Of total, 129 (49%) were receiving ICU level of care. No major bleeding events were observed. The incidence of CRNMB was 4.56% in the whole cohort, which did not differ significantly between the escalated prophylactic and therapeutic groups (12% and 12.12%, respectively). Patients treated with standard prophylaxis had less CRNMB (1.11%), but this was not statistically significant in a multivariate analysis that included other confounding factors such as age, sex, ethnicity, BMI, comorbidity, HASBLED bleeding risk, and sepsis induced coagulopathy score (SICS). The mortality rate was 12.6% in the whole cohort (7.22%, 21.21% and 26% in prophylactic, escalated prophylactic, and therapeutic dosage, respectively). Factors significantly associated with increased mortality included age and ICU level of care (HR 1.10, 95%CI [1.05, 1.15] and HR 20.42, 95%CI [2.84, 146.72], respectively). The use of therapeutic dose heparin and high-flow nasal cannula demonstrate a survival benefit in multivariate analysis (HR 0.13, 95%CI [0.04,0.44] and HR 0.23, 95%CI [0.07, 0.72], respectively; Figure 2). Breakthrough thrombosis occurred in 7 (2.66%) patients; 1 (0.56%), 1 (3.03%) and 5 (10%)) in prophylactic, escalated prophylactic and therapeutic dosage, respectively but very few diagnostic tests were performed during this time period. Duration of hospitalization was significantly longer in the therapeutic dose group when compared to escalated prophylaxis and standard prophylactic groups. Conclusion: In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH prophylaxis. By multivariate analysis, implementation of a d-dimer-titrated anticoagulation strategy was not associated with increased CRNMB. Therapeutic dose heparin based on a d-dimer-driven anticoagulation protocol was associated with a survival benefit in COVID19-infected patients. Limitations of this study include the retrospective observational nature and a lack of a uniform diagnostic protocol for patients with suspected VTE. Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population. Disclosures No relevant conflicts of interest to declare.

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Awards & honors

• Broad Clinical Research Fellow, 2020-2022