Enoxaparin Use in Hospitalized SARS-CoV-2-Positive Patients with Elevated D-Dimer: A Pilot Study

Introduction The SARS-CoV-2 is a human pathogenic coronavirus that causes a respiratory tract infection, which may lead to systemic hyper-inflammation that is associated with a hypercoagulable state. Anticoagulation as an adjunct may decrease thrombi formation. Objectives This study aims to evaluate the efficacy and safety of enoxaparin for the prevention of thrombotic events in hospitalized SARS-CoV-2 patients with elevated D-dimer. Methods A single-center retrospective cohort study was conducted to evaluate three enoxaparin dosing regimens: full treatment (1 mg/kg SC Q12H or 1.5 mg/kg SC Q24H), intermediate (.5 mg/kg SC Q12H or 1 mg/kg SC Q24H), and prophylaxis (40 mg SC Q24H). The primary endpoint evaluated the percentage of patients who developed a venous thromboembolism (VTE). The secondary endpoints evaluated the development of a major bleed, mechanical ventilation need, and death. Results Forty-five patients were included with 27, 8, and 10 participants in the full treatment, intermediate, and prophylaxis arms, respectively. Six patients developed a VTE: 3, 1, and 2 in the listed above groups, respectively ( P = .83). Twenty patients died: 11, 3, and 6, respectively ( P = .64). Four patients developed a major bleed: 1, 1, and 2, respectively ( P = .17). Six patients required intubation: 1, 2, and 3 in the arms, respectively ( P = .043). Conclusion The study did not find a difference in respect to the development of a VTE between the three investigated doses of anticoagulation. However, our findings suggest that treatment dose of enoxaparin might be associated with lower risk for mechanical ventilation in hospitalized COVID-19-positive patients with elevated D-dimer.

Clinical Outcomes of Emergent Laparotomies in Hypotensive Patients: 9-years Experience at a Single Level 1 Trauma Center

Purpose: The prognosis of an emergent laparotomy in hypotensive patients is poor. This study aimed to review the outcomes of hypotensive patients who had emergent laparotomies and elucidate the risk factors of mortality.Methods: Patients who underwent an emergent laparotomy from January 2011 to December 2019 were retrospectively reviewed. The exclusion criteria included initial systolic blood pressure > 90 mmHg, aged < 19 years, and cardiac arrest before the laparotomy. Patients were categorized into survival groups (survived or deceased). Univariate and multivariate analyses were conducted to determine the risk factors of mortality. The time from the laparotomy to death was also reviewed and the effect of organ injury.Results: There were 151 patient records, analyzed 106 survivors, and 45 deceased. The overall mortality was 29.8%. Liver injury was the main organ-related event leading to an emergent laparotomy, and most patients died in the early phase following the laparotomy. Following multivariate analysis, the Glasgow Coma Scale score [odds ratio (95% confidential interval) 0.733 (0.586-0.917), p = 0.007], total red blood cell transfusion volume in 24 hours[1.111 (1.049-1.176), p < 0.001], major bleed from the liver [3.931 (1.203-12.850), p = 0.023], and blood lactate [1.173 (1.009-1.362), p = 0.037] were identified as risk factors for mortality.Conclusion: Glasgow Coma Scale score, total red blood cell transfusion volume in 24 hours, major bleed from the liver, and lactate were identified as risk factors for mortality. Initial resuscitation and management of liver injuries have major importance following trauma.

Gender-Specific Outcomes after Percutaneous Left Atrial Appendage Closure - A Nationwide Readmission Database Analysis

Background: Thromboembolism-associated stroke is the most feared complication of Atrial fibrillation (AF). Percutaneous left atrial appendage closure (pLAAC) is indicated for stroke prevention in patients with AF who can’t tolerate long-term anticoagulation. We aim to study gender differences in peri-procedural and readmissions outcomes in pLAAC patients. Methods: Using the national readmission database from January 2016 to December 2018, AF patients undergoing the pLAAC procedure were identified. We used multivariate logistic regression analyses and time-to-event Cox regression analyses to conduct the study. Propensity matching with the Greedy method was done for the accuracy of results. Result: 28,819 patients were included in our study. Among them 11,946 (41.5%) were women and 16,873 (58.6%) were men. The mean age of overall population was 76.1 ± 8.5 years, with women ~ 1 year older than men. The overall rate of complications was higher in women (8.6% vs 6.6%, P<0.001), primarily driven by bleeding-related complications i.e., Major bleed (OR: 1.32 95% CI: 1.03-1.69, p=0.029), blood transfusion (OR: 1.45, 95% CI: 1.06-1.97, p=0.019) and cardiac tamponade (OR: 1.80, 95% CI: 1.13-2.89, p=0.014). Women had two times higher peri-procedural ischemic stroke. There was no difference in peri-procedural mortality. Women remained at 20% and 13% higher risk for readmission at 30 days and 6 months of discharge. Conclusion: Women had higher peri-procedural complications and were at higher risk of readmissions at 30 days and six months. However, there was no difference in mortality during the index hospitalization. Further studies are necessary to determine causality.

Evaluation of the Incidence and Risk Factors Associated with Bleeding Events in Patients Receiving Acalabrutinib Therapy

Background: Acalabrutinib is a more selective, second generation covalent binding Bruton tyrosine kinase (BTK) inhibitor. It was designed with the intent to mitigate adverse events (AEs) associated with ibrutinib, such as bleeding and cardiovascular events. In the phase 3 trial that that led to acalabrutinib approval in the front line setting for chronic lymphocytic leukemia (CLL), 37% and 2% of patients who received acalabrutinib monotherapy experienced grade 1-2 or ≥3 bleeding events, respectively. Currently, there are no long term studies evaluating the incidence of bleeding events associated with acalabrutinib. Therefore, the purpose of this study was to assess the incidence of bleeding events, and risk factors associated with bleeding events for patients treated with acalabrutinib for hematologic malignancies. Methods: This was a single center retrospective study conducted at The Ohio State University. Patients were included if they were ≥18 years old, diagnosed with a hematologic malignancy, and initiated on acalabrutinib (monotherapy or combination therapy) between January 1, 2010 and August 31, 2019. The International Society on Thrombosis and Haemostasis (ISTH) bleeding scale (no bleed, clinically non-relevant bleed, and clinically relevant/major bleed) and Common Terminology Criteria for Adverse Events V5.0 (CTCAE) were used to evaluate the grade and class of bleed events. Descriptive statistics were used to summarize demographic information and bleed events; univariable analysis was used to assess risk factors. Results: We analyzed 289 patients who received acalabrutinib for a hematologic malignancy. The main source of acalabrutinib was from clinical trials (85%) and the median acalabrutinib exposure time for all patients was 40.8 months (range: 0-81.6 months). 89% of patients had CLL, 2% had mantle cell lymphoma, and 9% had other non-Hodgkin's lymphoma. Additionally, 18% of patients had a prior bleed history and 51% were continued on concomitant medications that increase bleeding (Table 1). There were a total of 241 (83%) patients who experienced at least one bleed event. Per ISTH categorization, 143 (59%) patients' most severe bleed event was clinically non-relevant and 98 (41%) patients' was clinically relevant/major; cutaneous bleeds were most common in both groups, 71% and 31%, respectively. Only 6% of patients had a major bleed, hence, clinically relevant and major bleeds were analyzed together for the purpose of this study. There were a total of 633 bleed events that occurred in this study population; 76% were clinically-non relevant and only 3% (n=17) were CTCAE grade ≥3. Acalabrutinib was not discontinued or held for any clinically non-relevant bleeds, was discontinued for six (1%) clinically relevant/major bleeds, and held for 44 (7%) clinically relevant/major bleeds. Clinically relevant /major bleeds also resulted in discontinuations of concomitant anticoagulation and antiplatelet therapy in only 4% (n=24) of cases. 1263 procedures were identified and the incidence of clinically non-relevant and clinically relevant/major bleeds related to surgeries/procedures was 1% (n=12) and 1.3% (n=16), respectively. 10% of clinically non-relevant and 57% of clinically relevant/major bleeds led to hospitalizations, emergency room visits, or physician office visits; including two major CNS bleed events which resulted in death. The overall survival (OS) was not reached in the clinically non-relevant and clinically relevant/major bleed groups and was 14 months (95% CI 6-40) in the no bleed group (p=0.021). Univariate analysis showed that risk factors associated with a clinically relevant/major bleed included concomitant medications (OR 3.06, 95% CI 1.49-6.26) and prior bleed history (OR 4.40, 95% CI 1.45-13.40) (Table 3). Conclusions: Overall, our study had a long acalabrutinib exposure time and demonstrated a low incidence of grade ≥3 bleeds. There was also a low risk of bleeds related to procedures. The majority of bleeds were clinically non-relevant that did not result in significant treatment adjustments, hospitalizations, or death. This study identified prior bleed history and concomitant medications that increase bleeding as risk factors for bleeds and should be evaluated prior to starting acalabrutinib therapy. Our data supports acalabrutinib as a safe long-term treatment in regards to bleeds for patients with hematologic malignancies. Figure 1 Figure 1. Disclosures Wiczer: BTG Specialty Pharmaceuticals: Consultancy. Bhat: Beigene: Consultancy; Aptitude Health: Honoraria; AstraZeneca: Consultancy; Onclive: Honoraria. Byrd: Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Rogers: Janssen Pharmaceuticals, Inc: Research Funding; Pharmacyclics LLC: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy; Acerta Pharma: Consultancy; Innate Pharma: Consultancy; ovartis Pharmaceuticals Corporation: Research Funding; AbbVie Inc.: Consultancy, Research Funding. Woyach: AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding; Gilead Sciences Inc: Other: Data & Safety. Kittai: Bristol-Meyers Squibb: Consultancy; Janssen: Consultancy; Abbvie: Consultancy.

Thromboelastography utilization for dabigatran reversal in a patient with acute kidney injury

Purpose This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury. Summary An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient’s renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved. Conclusion Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.

Short dual antiplatelet strategy following left atrial appendage closure with Watchman and Watchman FLX: 1-year outcomes

Funding Acknowledgements Type of funding sources: None. Introduction Left atrial appendage occlusion (LAAO) is an effective stroke prevention strategy in patients with non-valvular atrial fibrillation and high bleeding risk. Oral anticoagulation or dual antiplatelet (DAPT) therapy is recommended for the period of device endothelisation but confers an increased bleeding risk. Purpose This study sought to examine the one-year outcomes of a short DAPT strategy following LAA occlusion in a large UK tertiary centre. Methods This retrospective study included all patients discharged on a short DAPT strategy (6-8 weeks) following a LAAO device implantation from January 2010 and December 2020 in our institution. Medical notes, procedural, and imaging reports were reviewed and adverse event rates were calculated at one year. Yearly bleeding risk was extrapolated from the Swedish National Cohort study according to CHA2DS2-VASc and HASBLED score. Results A total of 140 patients (106 Watchman and 36 Watchman-FLX) were discharged on a planned short DAPT strategy (age 74 ± 9 years, 70% male, 71% had previous bleeding on OAC, 95% previous major or life-threatening bleeding episodes, 52% previous ischaemic stroke, CHA2DS2-VASc score 4.5 ± 1.2, HASBLED score 3.2 ± 0.7). The median time to switching to either single antiplatelet (APT) or no ATP was 62 days. After first follow-up, 90% were either on SAPT (46.3% aspirin and 39.3% clopidogrel) or no ATP (6.4%). Seven (5%) patients had device-related thrombus on transoesophageal echocardiography and were started on anticoagulation and 4 (3.5%) patients remained on DAPT. At one year, of the 129 patients on a short DAPT strategy the composite of death, ischaemic stroke and non-procedural bleeding occurred in 11 patients (KM 8.9%; 95% CI, 3.7% -13.8%). Four patients (3.1/100 patient-years) suffered a major bleed and 3 (2.3/100 patient-years) had an ischaemic stroke on SAPT (mean time of 315 days). Compared to estimated annual stroke and bleeding risk adjusted for CHA2DS2-VASc and HASBLED score, this represents a 65% and 38% relative risk reduction in ischaemic stroke and major bleeding, respectively. Conclusion In our cohort, a short DAPT strategy following LAAO device appears safe with reduction of both thromboembolic and major bleeding events at 1-year. Abstract Figure 1

Risk of major bleeding by ethnicity and socioeconomic deprivation among 488,107 people in primary care: a cohort study

Background Antithrombotic medications (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. Methods Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Māori, the indigenous people of New Zealand) aged 30–79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n = 15,212), (2) CVD and no AF (n = 43,790), (3) no CVD or AF (n = 429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups. Results In all three subgroups (AF, CVD, no CVD/AF), Māori (adjHR 1.63 [1.39–1.91], 1.24 [1.09–1.42], 1.57 [95% CI 1.45–1.70], respectively), Pacific people (adjHR 1.90 [1.58–2.28], 1.30 [1.12–1.51], 1.62 [95% CI 1.49–1.75], respectively) and Chinese people (adjHR 1.53 [1.08–2.16], 1.15 [0.90–1.47], 1.13 [95% CI 1.01–1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Māori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [1.02–1.12], 1.07 [1.03–1.10], 1.10 [95% CI 1.08–1.12], respectively, for each increase in socioeconomic deprivation quintile). Conclusion Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD.

Bleeding events in COVID-19: the other side of the coin?

We present three cases of patients affected by severe SARS-CoV-2-related pneumonia treated with a low molecular weight heparin for prevention or treatment of pulmonary embolism, who presented a major bleed, in particular an ileopsoas haematoma that caused severe anaemia; in one case it was fatal. In the recent outbreak of novel coronavirus infection, significantly abnormal coagulation parameters in SARS-CoV-2 infection occur very often, but complications in the opposite direction such as bleeding diathesis are very rare. In these cases, there are different levels of gravity: for one patient the major bleed required the anticoagulant therapy to be stopped until bleeding stabilized, one patient needed interventional radiology and one patient died.

Abstract 27: Opioid Use Strongly Increases Incidence of Acute Kidney Injury in Patients With Acute Ischemic Stroke: An Analysis of 3.4 Million Admissions

Background: The relationship of opioid use with the incidence of acute ischemic stroke (AIS) and subsequent complications remains poorly understood. However, both opioid use and AIS have been independently associated with increased risk of subsequent acute kidney injury (AKI). In patients with AIS patients, AKI is associated with increased in-hospital and 10-year mortality. We evaluate whether opioid use in patients with AIS is associated with increased risk of AKI, near-term complications, mortality, and increased healthcare utilization. Methods: All records of patients within the Nationwide Inpatient Sample carrying a primary discharge diagnosis of AIS and secondary diagnosis of AKI between 2012-2014 were stratified by opioid status. The effect of opioid use on outcomes following AIS was analyzed after adjusting for confounders using logistic regression analysis. Results: Of 3,396,664 patients with AIS, 17,575 were diagnosed with an opioid-use disorder. There were 4,786 (27.2%) patients with AIS with opioid use that experienced in-hospital AKI compared to 426,823 (12.6%, p<0.01) patients without opioid use, despite patients with opioid use being younger (53 vs. 70 years, p<0.01) with fewer comorbidities, including CHD, CKD, hypertension, and diabetes. Patients with opioid use had longer hospitalizations (10 vs. 6.5 days; p < 0.01) and higher costs ($26,022 vs. $16,419, p < 0.01). Adjusting for confounding factors, opioid use among AIS patients was associated with an increased odds of AKI (odds ratio [OR]=2.0; 95% confidence interval [CI]=1.8-2.2; p<0.01), major bleed (OR=1.2; 95% CI=1.0-1.3; p=0.04), and in-hospital mortality (OR=1.3; 95% CI=1.1-1.5; p<0.01). Conclusions: We demonstrate that opioid use in patients with acute ischemic stroke is independently associated with twofold increased risk of AKI (27% vs. 12%, p<0.01; [OR]=2.0; 95% CI=1.8-2.2; p<0.01). As AKI is strongly associated with increased in-hospital and long-term mortality in patients with stroke, opioid use carries particularly significant implications for prognosis and management of the AIS population. Strategic measures designed to reduce incidence of AKI in AIS patients with opioid use may reduce complications, healthcare utilization, and mortality following stroke.