Evaluation of Unfractionated Heparin Dosing by Antifactor Xa During Targeted Temperature Management Post Cardiac Arrest

Purpose: To evaluate unfractionated heparin (UFH) dosing guided by antifactor Xa levels during targeted temperature management (TTM) post-cardiac arrest. Methods: Single-center, retrospective, observational study between January 1, 2014 and September 1, 2020. Patients initiated on TTM post-cardiac arrest and UFH were evaluated for inclusion. Patients included were ≥18 years of age and received weight-based UFH for ≥6 hours with 2 antifactor Xa levels drawn at target temperature. Excluded patients had no available temperature readings, received extracorporeal membrane oxygenation (ECMO) or factor Xa inhibitor (within 72 hours), or had hypertriglyceridemia or hyperbilirubinemia. The primary endpoint was to evaluate the proportion of patients that achieved a therapeutic antifactor Xa level between 0.3 and 0.7 IU/mL at steady state during TTM. Secondary endpoints included average UFH dose and average time to therapeutic antifactor Xa level at steady state; percent of first and total antifactor Xa levels subtherapeutic, therapeutic, and supratherapeutic during TTM. Results: A total of 73 patients met inclusion criteria. Of these, 21 patients achieved steady-state therapeutic antifactor Xa levels during TTM. The average time and dose to steady-state therapeutic antifactor Xa levels were 8.1 ± 4.5 hours and 9.9 ± 3.2 units/kg/hour. Overall, 61.7% of first and 47.4% of all antifactor Xa levels were supratherapeutic during TTM. Three (4.1%) patients experienced a major bleeding event. Conclusions: Guideline recommended UFH dosing, 12 or 18 units/kg/hour, during TTM resulted in more supratherapeutic antifactor Xa levels. Reduction of UFH infusion dose to 10 units/kg/hour may be required during TTM to maintain therapeutic antifactor Xa levels.

The risk of major bleeding event in patients with chronic kidney disease on pentoxifylline treatment

Patients with chronic kidney diseases (CKD) are often treated with antiplatelets due to aberrant haemostasis. This study aimed to evaluate the bleeding risk with CKD patients undergoing pentoxifylline (PTX) treatment with/without aspirin. In this retrospective study, we used Taiwan’s National Health Insurance Research Database to identify PTX treated CKD patients. Patients undergoing PTX treatment after CKD diagnosis were PTX group. A 1:4 age, sex and aspirin used condition matched CKD patients non-using PTX were identified as controls. The outcome was major bleeding event (MBE: intracranial haemorrhage (ICH) and gastrointestinal tract bleeding) during 2-year follow-up period. Risk factors were estimated using Cox regression for overall and stratified analysis. The PTX group had higher MBE risk than controls (hazard ratio (HR) 1.19; 95% confidence interval (CI) 0.94–1.50). In stratified analysis, hyperlipidaemia was a significant risk factor (HR: 1.42; 95% CI 1.01–2.01) of MBE. A daily PTX dose larger than 800 mg, females, non-regular aspirin usage, and ischaemic stroke were risk factors for MBE in PTX group. When prescribing PTX in CKD patients, bleeding should be closely monitored, especially in those with daily dose more than 800 mg, aspirin users, and with a history of ischaemic stroke.

Abstract 14931: Low-Dose Prasugrel Has Prognostic Superiority to Clopidogrel in High-Bleeding Risk Patients Undergoing Contemporary Percutaneous Coronary Intervention

Introduction: The combination of aspirin and P2Y12 receptor antagonist is the standard antiplatelet therapy after percutaneous coronary intervention (PCI). Previous trials reported that prasugrel reduced the risk of ischemic events, but increased bleeding events compared to clopidogrel. Hypothesis: The prognostic impact of low-dose prasugrel (3.75 mg/day), which the dose was determined by phase II trial, is different from that of clopidogrel, depending on patient’s bleeding risk. Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI. We analyzed 1,001 patients who received the combination of aspirin and prasugrel or clopidogrel after PCI. The primary endpoint was a composite of major bleeding event and major adverse cardiovascular and cerebrovascular events (MACCE) including any death, acute coronary syndrome, stent thrombosis, stroke and heart failure hospitalization. Results: There were 490 patients with high bleeding risk (HBR) and 511 patients with low bleeding risk (LBR), based on ARC-HBR criteria. In HBR patients, the Low-dose prasugrel group had significantly lower rates of MACCE (Log-rank, p=0.003) and the composite endpoint than the Clopidogrel group (p=0.001). While, in LBR patients, there was no significant difference in rates of MACCE or the composite endpoint between the groups (p=0.76, p=0.15, respectively), and a higher rate of major bleeding event in the Low-dose prasugrel group (p=0.002). With Cox proportional hazards analysis, low-dose prasugrel has still retained the superiority to clopidogrel regarding with the composite endpoint in HBR patients, even after adjusting with diverse covariates (hazard ratio: 0.33, 95% confidence interval: 0.16-0.65). Conclusion: In the multicenter cohort study in Japan, low-dose prasugrel showed a long-term prognostic superiority to clopidogrel only in HBR patients undergoing contemporary PCI.

Major Bleeding Outcomes for Admitted Immune Thrombocytopenia Patients with Platelets Less Than 10K: A Single Center Experience

Introduction Immune thrombocytopenia (ITP) is one of the most common causes of thrombocytopenia in adults. Majority of patients are asymptomatic or might have symptoms primarily related to mucocutaneous or minor bleeding events, while severe bleeding is uncommon. ITP patients who develop severe bleeding require urgent hospitalization, but asymptomatic/minor bleeding patients might be successfully treated as outpatient. In several occasions, the latter group of patients are admitted to the hospital to initiate treatment when their platelets are very low (i.e. less than 10K). In this study we aimed to evaluate the incidence of major bleeding and medical necessity for admitting this group to the hospital. Methods We conducted a retrospective chart review of 559 charts with an ICD code of ITP between March 2017 to March 2020. We excluded all patients who presented with a platelet above 10K, other co-existing hematological disorders or malignancies, first presentation with platelets less than 10K with no prior known history of ITP, and charts of patients who left against medical advice prior to initiation of treatment. The definition of major bleeding included intracranial hemorrhage, or any bleeding with more than 1 gm hemoglobin drop. Minor bleeding included epistaxis, gum bleeding, hematuria, vaginal or minor GI bleeding that didn't result in hemoglobin drop. We found a total of 66 ITP patients who were admitted to the hospital because of platelet count of less than 10K, of which 54 had minor or no bleeding episode, while 12 patients presented with major bleeding episode. Results Between the period of March 2017 to March 2020, a total of 66 patients with a known history of ITP were admitted to the hospital with platelet count of less than 10K, of which 54 patients (82%) had either only minor bleeding (n=10), or no evidence of bleeding (n=44) and 12 patients (18%) presented with major bleeding. The major bleeding events were distributed as follows: Hematuria due to kidney stone (n=1), traumatic ICH ((n=4), spontaneous ICH (n=1), and GI bleed (colon mass (n=1), erosive gastropathy(n=1), angiodysplasia (n=1), esophageal varices (n=2), and gastric ulcer (n=1)). None of the asymptomatic/minor bleeding patients developed any major bleeding event before, during or after hospitalization. The average LOS for asymptomatic/minor bleeding patients was 4.65 days (range 1-45 days), compared to 9.14 days (range 2-20 days) for patients with major bleeding. All the 12 patients (100%) with major bleeding received platelet transfusions during hospitalization, while 23 asymptomatic/minor bleeding patients (42%) received platelet transfusion. Discussion Major bleeding in patients with acute ITP is usually a clear indication for hospitalization, however there is lack of data to support admitting asymptomatic/minor bleeding ITP patients when platelets are less than 10K. Our data showed that no major bleeding event has developed in asymptomatic/minor bleeding patients at time of presentation, during hospitalization or after discharge. All 12 patients with major bleeding presented with a bleeding event that warranted their admission, of which 1 patient had spontaneous bleeding, while the rest had a clear medical reason for the major bleeding, which was likely exacerbated by thrombocytopenia. Since assessing the risk of bleeding is an important step in considering prophylactic platelet transfusion for those with platelets less than 10K, 42% of asymptomatic/minor bleeding patients received platelet transfusion during admission indicating that more than half didn't have high risk features. Inpatient hospitalization carries a high financial burden on both the patient and the healthcare system, increases the risk of hospital acquired infections and in-hospital complications. Asymptomatic/Minor bleeding patients in our study had average LOS of 4.65 days, and all were treated with regimens that can be given as an outpatient including steroids, IVIG, and in some occasions Rituximab and/or thrombopoietin stimulating agents increasing the cost of their hospital stay. Based on our observation, we are able to conclude that this particular group of patients would possibly benefit from close monitoring of signs and symptoms, labs, and treatment all in the outpatient setting. Further studies are needed to evaluate the cost effectiveness and long-term outcome in these patients. Disclosures No relevant conflicts of interest to declare.

Prognostic implication of baseline and 30-day anemia in patients with coronary artery disease undergoing percutaneous coronary intervention

Background Anemia correlates with the risk of ischemic and bleeding event in coronary artery disease (CAD) following percutaneous coronary intervention (PCI). Methods We defined anemia by World Health Organization criteria (hemoglobin <13 g/dL in men and <12 g/dL in women). Major bleeding event was defined as Bleeding Academic Research Consortium (BARC) 3 or 5. Major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, non-fatal myocardial infarct, and revascularization. The primary end-point was the MACE rate and the major bleeding rate. Results Among the 5,809 patients who underwent the PCI, 32.1% of the baseline anemia and 33.5% of the 30-day anemia were identified. With a median follow-up of 26.8 [15.9–42.3] months, and the MACE rate was 11.6% and the major bleeding event rate was 2.2%. 30-day anemia rather than baseline anemia showed a significant risk of MACE and major bleeding event (MACE, adjusted HR 1.28, p=0.036 vs. adjusted HR 1.09, p=0.389; major bleeding event, adjusted HR 2.72, p<0.001 vs. adjusted HR 1.73, p=0.006) (Figure). The MACE and major bleeding event rate at 5-year was significantly increased in patients with 30-day anemia (18.4% vs. 12.1%, p<0.001; 10.4% vs. 2.3%, p<0.001). Conclusion Anemia during the first 30-day was strongly associated with higher rate of long-term MACE and major bleeding event. These findings could have a clinical relevance in making a pharmacologic strategies to avoid the future ischemic and bleeding event following PCI. Funding Acknowledgement Type of funding source: None

LO94: Evaluation of stroke and bleeding outcomes among patients managed in the emergency department for newly diagnosed atrial fibrillation

Introduction: Atrial Fibrillation (AF) is the most common arrhythmia seen in patients presenting to the emergency department (ED). AF increases the risk of ischemic stroke which can be mitigated by anticoagulant prescription. National guidelines advise that emergency physicians initiate anticoagulation when AF is first diagnosed. We aimed to evaluate the 90-day incidence of stroke and major bleeding among emergency patients discharged home with a new diagnosis of AF. Methods: This was a health records review of patients diagnosed with AF in two EDs. We included patients ≥ age 18, with a new diagnosis of AF who were discharged from the ED, between 1st May 2014 and 1st May 2017. Using a structure review we collected data on CHADS65 and CHADS2 scores, contraindications to direct oral anticoagulant (DOAC) prescription and initiation of anticoagulation in the ED. Patient charts were reviewed for the diagnosis of stroke, transient ischemic attack (TIA), ischemic gut, ischemic limb or other systemic embolism within 90 days of the index ED presentation. We extracted data on major bleeding events within 90 days, defined by the International Society of Thrombosis and Haemostasis criteria. All data were extracted in duplicate for validation. Results: We identified 399 patients fulfilling the inclusion criteria, median age 68 (IQR 57-79), 213 (53%) male. 11 patients were already prescribed an anticoagulant for another indication and 19 had a contraindication to prescription of a DOAC. 48/299 (16%) CHADS65 positive patients were initiated on an anticoagulant, 3 of whom had a contra-indication to initiation of anticoagulation in the ED (1 dual antiplatelet therapy, 2 liver cirrhosis). 1/100 CHADS65 negative patients was initiated on anticoagulation. The median CHADS2 score was 1 (IQR 0-2). Among the 49 patients initiated on anticoagulation, 3 patients had a stroke/TIA within 90 days, 6.1% (95% CI; 2.1-16.5%). There were no bleeding events 0.0% (95% CI; 0.0-7.3%). Among the 350 patients who were not initiated on anticoagulation in the ED, 4 patients had a stroke/TIA 1.1% (95% CI; 1.1-2.9%) within 90 days and 2 patients had a major bleeding event. Conclusion: Prescription of anticoagulation for new diagnoses of AF was under-utilized in these EDs. The 90-day stroke/TIA rate was high, even among those given an anticoagulant prescription in the ED. No patient had an anticoagulant-associated bleeding event.

Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis: risk factors and antithrombotic treatment

Introduction The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events.The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event.All patients performing an bioSAVR or a TAVI 2008–2014 were identified in the SWEDEHEART registry and included in the study (n = 10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry.The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy.Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.

Patient Harm from Repetitive Blood Draws and Blood Waste in the ICU: A Retrospective Cohort Study

Introduction: Frequent blood testing in the intensive care unit (ICU) is instrumental to patient diagnosis, monitoring, and titration of invasive therapies. However, there is a growing appreciation that a significant proportion of ICU blood tests are reflexive and unnecessary.1,2 Serial phlebotomy is associated with extended hospital length of stay and acquired anemia in the general hospital population.3 Since patients in the ICU are prone to developing anemia,4,5 they are likely at increased risk of harm from serial phlebotomy. In response, multiple recent campaigns advocate for physician restraint in laboratory test ordering.6,7 However, relatively little is known about the effect of excessive phlebotomy on outcomes in critically ill patients. Better understanding of ICU phlebotomy practices, and harms associated with serial testing, is important in planning, implementing, and evaluating phlebotomy reduction interventions. Objectives: 1) Quantify average daily phlebotomy volume for ICU patients including blood discarded as waste when accessing vascular devices. 2) Identify if average daily phlebotomy volume is an independent risk factor for ICU acquired anemia (hemoglobin < 80 g/L) or the need for red blood cell transfusion. 3) Explore the relationship between daily phlebotomy volume and hospital mortality. Methods: This was a retrospective cohort study at an academic tertiary care center in Toronto, Ontario, utilizing hospital administrative data, laboratory data, and select chart review. Index Medical Surgical ICU admissions between September 2014 and August 2015 with an ICU stay of three days or greater were included. Major bleeding events were defined as a hemoglobin drop of 30 g/L within a 24 hour period. Average daily phlebotomy volumes were calculated using the number of samples received by the lab multiplied by standard blood volumes required for each sample type. A bedside prospective audit was conducted in March 2018 to quantify average blood volume discarded as waste during phlebotomy. Blood discard/waste data were summarized with descriptive statistics, but not included in further analysis. Multivariable logistic regression was used to study the association between average daily phlebotomy volume and each of: nadir hemoglobin (< 80 g/L), the need for red blood cell transfusion, and hospital mortality. Patients with a major bleeding event were excluded from the regression. Control variables included sex, age, ICU length of stay, admission hemoglobin, and admission Sequential Organ Failure Assessment (SOFA) score. Results: There were a total of 525 index patient admissions, mean age 62.1 yr, 41% female (Table 1). Fifty-two (52) patients had a major bleeding event in the ICU. Mean phlebotomy volume per patient day was 28.3 mL (95% CI 27.4 - 29.1 mL, stdev 10.1 mL). Mean bedside waste during the phlebotomy audit (total of 144 blood draws) varied by vascular access: 3.9 mL for arterial, 5.5 mL for central venous, and 6.25 mL for peripherally inserted catheters. The mean estimated daily bedside waste for phlebotomy was 14.8 mL per patient day. Outcomes of logistical regression, excluding patients with major bleeding events, are summarized in Table 2. Average daily phlebotomy volume (mL) was predictive of nadir hemoglobin < 80 g/L (parameter estimate 0.091, p <0.001), the need for red blood cell transfusion (0.092, p<0.001), and inpatient mortality (0.053, <0.001). For every 5 mL increase in average daily phlebotomy, the odds ratio (OR) for nadir hemoglobin < 80 g/L was 1.58 (95% CI 1.31 - 1.90) and the OR for a red cell transfusion was 1.58 (95% CI 1.33 - 1.87). Conclusion: Daily ICU phlebotomy volume is associated with ICU acquired anemia and the need for red blood cell transfusion, including in a multivariable model with patient demographics, major bleeding events, and severity of illness as estimated by day 1 SOFA score. However, the ICU admission SOFA score was only weakly predictive of mortality, and the unexpected association between average daily phlebotomy and mortality needs to be further explored. It is possible that in this data set day 1 SOFA score did not completely control for severity of illness. Our findings support the need for ongoing phlebotomy stewardship interventions in the ICU. We suggest ICU acquired anemia and the need for red blood cell transfusion are appropriate patient outcome measures to evaluate stewardship interventions. Disclosures No relevant conflicts of interest to declare.

P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p<0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p<0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p<0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p<0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

P5009The major bleeding event is the stronger predictor of long term mortality rather than the coronary event in the secondary prevention of ischemic heart disease in Japan

Background/Introduction Secondary prevention for ischemic heart disease (IHD) is important part in health care. To improve the risk factor control with general practitioners, we decided to set up a unique referral system to connect the hospital and outpatient clinics. Purpose Long term prognosis of IHD patients is unknown. The aims of this study are introducing our unique audit referral system and showing the long term prognosis of IHD patients with optimal second prevention therapy. Methods IHD patient registry was established in 2009 to connect cardiologists in the core hospitals and more than 200 general practitioners in Shizuoka city. To audit the treatment of general practitioners, we adopted a circulation type cooperative form. Target values of risk factors are as follows; low-density-lipoprotein cholesterol (LDL-C) concentration less than 100 mg/dl, HbA1c in diabetic patients less than 7%, systolic blood pressure (SBP) less than 130mmHg, and diastolic blood pressure (DBP) less than 80mmHg. General practitioners are required to introduce registered patients at least once a year even there is no event. Mean follow-up interval was 2001±794 days. Results We could follow 1240 patients who were registered from May 2009 to December 2013 and followed by at least one visit to the hospital in the prescribed manner until September 2018. Mean age was 77.3±10.6 years old, and 39.6% of them had old myocardial infarction. Latest risk factor controls are as follows; LDL-C 88.0±21.3mg/dl, HbA1c control in diabetic patients 7.0±1.1%, SBP and DBP 133.7±16.5 and 75.0±11.8mmHg respectively. Cumulative incidence of all-cause death was 10.8%, cardiac death was 1.5%, and coronary event (combination of cardiac death, myocardial infarction, angina pectoris which need hospitalization, and any lesion revascularization) was 15.8%. Cumulative incidence of major bleeding was 2.6%. The patients were divided into three groups without overlapping; major bleeding group (n=34), coronary event group (n=195), and event-free group (n=1049). The nonparametric test showed significant differences between three groups concerning age (p=0.026), the rate of using antithrombotic drugs (p<0.001) and mortality (p=0.017). Kaplan-Meier method concerning all-cause death showed a significant difference between event-free group and major bleeding group (log rank p=0.002), and coronary event group and major bleeding group (p=0.026), while no statistical difference between event-free group and coronary event group. Cumulative survival rate Conclusions Our unique referral system revealed long term events in the stable IHD patients in Japan. The major bleeding event is a strong predictor of long term mortality in IHD patients rather than the coronary event.