Abstract MP4: Ticagrelor Plus Aspirin Versus Aspirin Alone in Acute Ischemic Stroke or TIA - Analysis of Bleeding Events in the THALES Trial

Introduction: In the THALES trial, ticagrelor and aspirin was superior to aspirin alone in reducing the primary endpoint of stroke or death, and subsequent disabling strokes, but increased risk of bleeding, as expected for dual antiplatelet therapy. Aim: Present the bleeding profile of ticagrelor in combination with aspirin in patients with acute cerebrovascular events. Methods: The THALES trial randomized patients with non-cardioembolic, non-severe ischemic stroke (NIHSS≤5) or high-risk TIA to ticagrelor (180mg loading dose on day 1 followed by 90mg twice daily until day 30) or placebo within 24h of symptom onset in 28 countries. All patients received aspirin 300-325mg on day 1 followed by 75-100mg daily until day 30. Primary safety endpoint was time to severe bleeding, defined by GUSTO criteria, within 30 days. Analyses were by intention to treat. (ClinicalTrials.gov number, NCT03354429). Results: Among 11016 patients randomized, 28 (0.5%) in the ticagrelor+aspirin group (T+A) and 7 (0.1%) in the aspirin group (A) had a severe bleeding event; HR 3.99 (1.74-9.14); p=0.001. Among these, 22 (0.4%) (T+A) vs 6 (0.1%) (A) were fatal or intracranial hemorrhages (ICHs) and 6 (0.1%) (T+A) vs 1 (<0.1%) (A) non-fatal events with hemodynamic compromise. ICHs included 10 (0.2%) (T+A) vs 2 (<0.1%) (A) hemorrhagic strokes and 4 (0.1%) (T+A) vs 2 (<0.1%) (A) symptomatic haemorrhagic transformations of ischemic stroke and other ICHs. Most severe bleeding events were spontaneous; 1 (T+A) and 2 (A) were traumatic and 1 in each treatment group were procedural. No predefined subgroup was associated with severe bleeding risk though analyses were limited by a small number of events. Moderate/severe bleeding events occurred in 36 (0.7%) (T+A) vs 11 (0.2%) (A) patients. Bleeding leading to discontinuation occurred in 152 (2.8%) (T+A) vs 32 (0.6%) (A) patients. Conclusion: While the rate of severe bleeding in the patients with acute ischemic stroke or TIA was low, patients randomized to receive ticagrelor more often experienced severe bleeding events. No subgroup with different bleeding risk could be identified. Given the high risk of disability following a subsequent stroke, the benefit of adding ticagrelor to aspirin in reducing subsequent stroke appears to outweigh the risk of bleeding.

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Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke

The Neurohospitalist ◽

10.1177/1941874419879813 ◽

2019 ◽

Vol 10 (3) ◽

pp. 176-180

Author(s):

Michael J. Erdman ◽

K. Erin Davidson ◽

J. Tyler Haller ◽

Samarth Shah ◽

Whitney Gross ◽

...

Keyword(s):

African American ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Bleeding Risk ◽

International Normalized Ratio ◽

Occurrence Rate ◽

Bleeding Events ◽

Point Increase ◽

Increased Risk ◽

African American Race

Background/Objective: Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. Methods: We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. Results and Conclusions: Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

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External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th16-10-0810 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1164-1170 ◽

Cited By ~ 33

Author(s):

Frederikus A. Klok ◽

Stefano Barco ◽

Stavros V. Konstantinides

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Major Bleeding ◽

External Validation ◽

Chronic Phase ◽

Bleeding Risk ◽

Bleeding Events ◽

Risk Of Bleeding ◽

Increased Risk ◽

Study Population

SummaryOne of the main determinants of establishing the optimal treatment duration of patients with venous thromboembolism (VTE) is the risk of major bleeding during long-term anticoagulant therapy. The 6-variable VTE-BLEED score was recently developed to enable estimation of this bleeding risk. This study aimed at externally validating VTE-BLEED. This was a post-hoc study of the randomised, double-blind, double-dummy, Hokusai-VTE study that compared edoxaban versus warfarin for treatment of VTE. VTE-BLEED was calculated in all 8,240 study patients. The numbers of adjudicated major bleeding events during ‘stable anticoagulation’, i. e. occurring after day 30, in patients with low (total score <2 points) and high risk of bleeding (total score ≥2 points) were compared for the overall study population, patients randomised to edoxaban or warfarin, and for important patient subcategories. During ‘stable’ anticoagulation, major bleeding occurred in 1.02% (40/3,903) and 0.82% (32/3,899) of patients treated with warfarin and edoxaban, respectively. For the overall study population, the risks of bleeding in the low and high risk groups were 0.51% and 2.03%, respectively, for an odds ratio (OR) of 4.04 (95% confidence interval [CI]: 2.51–6.48). ORs were 5.04 (95%CI: 2.62–9.69) and 3.09 (95%CI: 1.54–6.22) for warfarin and edoxaban, respectively. VTE-BLEED was consistently able to identify patients at a 2.5- to 11-fold higher bleeding risk across all the predefined subcategories, as well as for the treatment period between day 30 to day 180, and beyond day 180. In conclusion, patients identified as high risk by VTE-BLEED had a four-fold increased risk of bleeding during the chronic phase of treatment.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Abstract P25: Safety of Ticagrelor in Moderate to Severe Acute Ischemic Stroke: A Single-Center Retrospective Review

Stroke ◽

10.1161/str.52.suppl_1.p25 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Stephen W English ◽

David Landzberg ◽

Nirav Bhatt ◽

Michael Frankel ◽

Digvijaya Navalkele

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Major Bleeding ◽

Mechanical Thrombectomy ◽

Categorical Variables ◽

Severe Bleeding ◽

Large Artery ◽

Inpatient Stay ◽

Increased Risk

Introduction: Ticagrelor with aspirin has been recently shown to reduce the risk of stroke or death compared to aspirin alone in patients with high risk TIAs and mild strokes. However, this benefit is offset by increased risk of severe bleeding. We sought to evaluate the safety of ticagrelor in patients with moderate to severe ischemic stroke. Methods: This was a retrospective cohort study of adults discharged on ticagrelor after presenting with acute ischemic stroke and NIHSS > 5 from January 2016 to December 2019 at a large, urban, academic comprehensive stroke center. Patients were excluded if they underwent carotid or intracranial angioplasty and/or stenting, or carotid endarterectomy during admission. Baseline clinical characteristics, imaging, and outcomes were reviewed. Data was organized into continuous and categorical variables. Results: Sixty-one patients met inclusion and exclusion criteria. Median age was 61 (IQR, 52-68) years; 33 (54%) were men, and 33 (54%) were African American. Median NIHSS was 11 (IQR, 8-15). Fourteen (23%) patients received IV Alteplase and 35 (57%) patients underwent mechanical thrombectomy. Five (8%) patients received both IV Alteplase and mechanical thrombectomy. Median ticagrelor start date was hospital day 1 (IQR, 0-3). Large artery atherosclerosis was presumed etiology in 53 (87%) patients. No patients experienced neurologic worsening, recurrent stroke, sICH, or major bleeding during inpatient stay. Sixty (98%) patients were on aspirin and ticagrelor at discharge. Follow-up information was available for 53 (87%) patients for a median duration of 3 (IQR, 2-6) months. Following discharge, 3 (5%) patients experienced recurrent ischemic stroke despite being compliant. One (2%) patient experienced major bleeding—gastrointestinal hemorrhage requiring transfusion—two months after hospital discharge. Conclusions: This study highlights the potential expanding role for ticagrelor in secondary stroke prevention in patients with moderate to severe stroke. Early ticagrelor use did not result in sICH during inpatient stay—and only 1 major bleeding event on follow-up—in our cohort. While further research in this area is needed, these findings present an exciting opportunity for future prospective studies.

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P1558Clinical utility of the PRECISE-DAPT score in the prediction of hemorrhagic events in elderly patients with acute coronary syndrome

European Heart Journal ◽

10.1093/eurheartj/ehz748.0318 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Rioboo ◽

E Abuassi Alnakeeb ◽

S Raposeiras Roubin ◽

I Munoz Pousa ◽

M Cespon Fernandez ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

High Risk ◽

Elderly Patients ◽

Age Groups ◽

Bleeding Event ◽

Bleeding Risk ◽

The Elderly ◽

Coronary Syndrome ◽

Risk Of Bleeding ◽

Risk Patients

Abstract Introduction The clinical utility and validity of the PRECISE-DAPT bleeding risk score for elderly patients with acute coronary syndrome (ACS) is unknown. We investigated the previous aspect in a contemporary population treated with percutaneous coronary intervention (PCI) and dual antiplatelet therapy (DAPT) at discharge. Methods Retrospectively, from 2010 to 2016, we studied 3,814 consecutive patients with the diagnosis of ACS. All patients were treated with in-hospital PCI and DAPT at discharge. Elderly was defined if patients aged ≥75 years. Patients were categorized into three risk strata according to their PRECISE-DAPT score (very low-low: <17 points, moderate: 18–24 points, and high risk: ≥25 points). We included the first bleeding event occurred during the first year after discharge. Bleeding events were defined according to the BARC classification system, and divided into two subgroups: BARC 2–5 and BARC 3–5. The ability to separate high bleeding risk patients from lower bleeding risk patients was checked by the cumulative incidence function curves and compared using the Fine-Gray test, thus adjusting for death (non-bleeding related) as a competing risk. Discrimination (C statistic) and calibration (Hosmer-Lemeshow test) were used to test the predictive capacity of the score in pts aged ≥75 years and <75 years. Results 25.2% (n=961/3814) were ≥75 years old, 38.4% of them were women. DAPT duration was 11.5 (interquartile range [IQR] 2.5–13.7) vs. 12.0 (RIQ 8.2–14.1) months in the elderly vs. younger; (p<0.001). 92.5% (n=889) of the elderly were at high risk of bleeding (PRECISE-DAPT≥25 points), compared to 21.3% (n=607) of the youngest. The incidence of BARC 2–5 and BARC 3–5 was 7.4% and 2.7% in the elderly compared to 5.1% and 1.4% among the younger patients (p<0.001). The figure shows the ability of the PRECISE-DAPT score at capturing the risk of BARC 2–5 bleeding (panel A and B), in both age groups. Using the cut-off point ≥25, the effect in the prediction of BARC 2–5 bleeding and BARC 3–5 did not differ significantly between the elderly and those <75 years: sHR = 1.9 (95% CI: 1.2–6.00) in the elderly vs. 1.8 (95% CI: 1.3–2.5) in the other group (p=0.99) and sHR = 3.3 (95% CI: 1.9–6.0) vs. 3.6 (95% CI: 1.9–6.7) (p=0.83), respectively. There were no significant differences between the elderly and those under 75 years in terms of statistical C values either for BARC 2–5 bleeding (0.60 vs. 0.58) or BARC 3–5 bleeding (0.64 vs. 0.67). The score performed well in term of calibration in both groups (all p-values >0.3). Conclusion Although the use of PRECISE-DAPT resulted in classifying the majority of elderly patients at high risk of bleeding and despite exhibiting modest discriminative power, it performed well at classifying patients according to their risk of 1-year out-of-hospital bleeding in both age groups. PRECISE-DAPT appears to identify the truly low risk patients among the elderly, as compared to the younger group.

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Clinical impact of CREDO-kyoto risk score on in-hospital bleeding in patients with acute coronary syndrome

European Heart Journal ◽

10.1093/eurheartj/ehab724.1412 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

Y Minematsu ◽

M Natsuaki ◽

G Yoshioka ◽

K Shinzato ◽

Y Nishimura ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

High Risk ◽

Risk Score ◽

Major Bleeding ◽

Bleeding Risk ◽

Risk Groups ◽

University Hospital ◽

Severe Bleeding ◽

Bleeding Events ◽

Coronary Syndrome

Abstract Background/Introduction CREDO-Kyoto bleeding risk score was developed to predict the post-discharge bleeding events in patients with percutaneous coronary intervention. However, there were limited reports of the effectiveness of this score to predict the in-hospital bleeding events in patients with acute coronary syndrome (ACS). Methods We evaluated 562 consecutive ACS patients in Saga university hospital between 2014 and 2019. Primary outcome was major bleeding during hospitalization. Major bleeding was defined as the GUSTO moderate/severe bleeding. Patients were classified into three groups according to the CREDO-Kyoto bleeding risk score (low, intermediate and high). Results Major bleeding events occurred in 12.1% of all patients during hospitalization. Patients in the high risk group (n=22) had significantly higher incidence of major bleeding than those in the intermediate (n=113) and the low risk groups (n=427) (22.7%, 18.6%, versus 9.8%, respectively, p=0.018, see figure). Multivariate analysis showed that intermediate and high risk groups were independent predictors for the in-hospital major bleeding. Conclusions CREDO-Kyoto risk score successfully identified high risk ACS patients for the major bleeding during hospitalization. FUNDunding Acknowledgement Type of funding sources: None. Results

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Bleeding Risk in a Cohort of Ambulatory Cancer Patients Receiving Outpatient Prophylactic Anticoagulation for Venous Thrombosis Prevention

Blood ◽

10.1182/blood-2019-128831 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 709-709

Author(s):

Andrew B Wilks ◽

Daniel Douce ◽

Steven Ades ◽

Mary Cushman ◽

Neil A. Zakai ◽

...

Keyword(s):

Lung Cancer ◽

High Risk ◽

Cancer Patients ◽

Major Bleeding ◽

Bleeding Risk ◽

Bleeding Events ◽

Major Bleed ◽

Prophylactic Dose ◽

Increased Risk ◽

Prophylactic Anticoagulation

Background: Recent clinical trials have evaluated the safety and efficacy of direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) prophylaxis in cancer outpatients at high risk for thrombosis. Bleeding risk in these trials were approximately 2% over the first 6 months of therapy. For individual patients, the utility of prophylactic anticoagulation (AC) depends on an acceptable safety profile between bleeding and thrombosis. We investigated whether ambulatory cancer patients on contemporary cancer-directed therapies and prophylactic AC had an increased risk of major bleeds over the first 6 months of therapy. Methods: As part of a single-center prospective cohort study, we assessed consecutive ambulatory patients initiating cancer-directed treatment, risk-stratified these patients for VTE using the Khorana score and educated them about VTE. High risk patients (Khorana score ≥3) were offered prophylactic AC. Major bleeding events and minor bleeding events (based on ISTH standard definitions) were prospectively captured via billing code screening and confirmed by physician review of the medical record. Logistic regression was used to compare the odds of developing a major bleed within 6 months in those who received prophylactic AC compared to those that did not. Results: A total of 1,210 patients were enrolled from October 2015 - June 2018, of which, 640 were women (52.9%). The most common cancers were gastrointestinal 270 (22%), lung 213 (18%), and breast 198 (16%). There were 393 patients (32%) with a Khorana score of 0, 706 (58%) with a Khorana score of 1-2, and 111 (9%) with a score of ≥3. A total of 421 patients received any AC (LMWH or DOAC). Of these, 282 received a prophylactic dose anticoagulant and 139 were receiving a full dose anticoagulant prior to enrolling for other medical reasons. Prophylactic dose anticoagulants prescribed included apixaban in 107 (41%), rivaroxaban in 6 (2.3%), enoxaparin in 119 (45.7%), and other heparin products in 50 (19.2%). A total of 27 (2.33%) major bleeds and 22 (1.81%) minor bleeds occurred within the first 6 months of starting therapy. Of these bleeding events, 8 (2.8%) occurred in those on prophylactic AC, and 6 (4.3%) occurred in those on full dose AC. The odds ratio (OR) of developing a major bleed on any type of AC was 1.78 [CI 0.817-3.88]. The OR of major bleeding on prophylactic AC was 1.49 [CI 0.64-3.479]. The OR of major bleed was highest in lung cancer patients on prophylactic AC (OR 2.81, CI 1.27-6.25). Men, when compared to women, were more likely to bleed on prophylactic AC in the first six month (OR 0.2; CI 0.07-0.52). The OR for major bleed with each 1 year increase in age was 1.02 (CI 0.99, 1.06). The OR of bleeding with a high risk Khorana score (≥3) compared to a lower score was 1.04 (CI 0.73-1.50). Conclusion: During the first six months of therapy, prophylactic AC was associated with an increased risk of major bleeding events in patients on cancer-directed therapy. In this study, the rate of major bleeding was similar as compared to published clinical trials. Neither age nor higher Khorana score were associated with an increased risk of major bleeds in patients on prophylactic AC. The finding that men, when compared to women, and patients with lung cancer may have an increased risk of major bleeding while on prophylactic AC and cancer-directed chemotherapy suggests these groups may warrant both increased education and monitoring to ensure safety while on prophylactic AC. Disclosures No relevant conflicts of interest to declare.

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Abstract 159: Evaluation of Clinical Outcomes among Nonvalvular Atrial Fibrillation Patients Treated With Warfarin or Rivaroxaban Stratified by Presence or Absence of CKD in a Claims Database

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.10.suppl_3.159 ◽

2017 ◽

Vol 10 (suppl_3) ◽

Author(s):

Matthew R Weir ◽

Lloyd Haskell ◽

Jeffrey S Berger ◽

Veronica Ashton ◽

François Laliberté ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Bleeding Event ◽

Data Availability ◽

Thromboembolic Events ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Claims Database ◽

Increased Risk

Introduction: Renal functional impairment is linked to an increased risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF) treated with warfarin and rivaroxaban. Anticoagulants such as warfarin and rivaroxaban are often recommended to reduce the risk of stroke in NVAF patients. The purpose of this study was to evaluate and compare thromboembolic and bleeding event rates for warfarin and rivaroxaban patients stratified by presence of chronic kidney disease (CKD). Methods: Claims from the IMS Health Real-World Data Adjudicated Claims database from 05/2011-6/2015 were analyzed. Adult patients with NVAF who had ≥6 months of baseline data prior to the first dispensing of warfarin or rivaroxaban after 11/2011 were included. Patients were followed until the end of index therapy or end of data availability/insurance coverage. Outcomes were stratified by presence of CKD for ischemic stroke, major bleeding, and a composite measure of thromboembolic events (ischemic stroke, myocardial infarction (MI) or venous thromboembolism (VTE)) and analyzed using hazard ratios (HRs). Adjustments for confounding were made with inverse probability of treatment weights (IPTW). Results: The analysis included 39,872 rivaroxaban (9.0% [3,572 of 39,872] with CKD) and 48,637 warfarin patients (16.9% [8,230 of 48,637] with CKD). As expected, thromboembolic and bleeding events were more common in patients with CKD than those without CKD. Rivaroxaban patients had significantly lower risk of ischemic stroke, both in the overall population (HR = 0.79 [0.68-0.90], p=0.0008) and for those with CKD (HR = 0.55 [0.40-0.77], p=0.0004). A composite of thromboembolic events were lower with rivaroxaban irrespective of CKD. Major bleeding rates were comparable across all groups. Table 1 reports incidence rates and HRs stratified by presence of CKD. Conclusions: This study suggests that, in an adult population with NVAF, rivaroxaban-treated patients had fewer ischemic strokes across all patients, including patients with renal impairment. Rivaroxaban-treated patients also had significantly better outcomes for the composite (VTE, MI, or stroke) measure across all groups. Bleeding rates were comparable across all groups.

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Abstract 17598: More Than One in Five Older Veterans are Hospitalized for Bleeding Following Initiation of Warfarin for Atrial Fibrillation

Circulation ◽

10.1161/circ.132.suppl_3.17598 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

John A Dodson ◽

Andrew Petrone ◽

David Gagnon ◽

Mary E Tinetti ◽

Harlan M Krumholz ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Bleeding Event ◽

Bleeding Risk ◽

Bleeding Events ◽

Time Period ◽

Increased Risk ◽

Anticoagulation Clinics ◽

Comorbidity Burden

Introduction: Clinicians are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation (AF) due to concerns over bleeding risk. Hypothesis: As many data on bleeding events are from trials of rigorously selected patients, we hypothesized that major bleeding events (requiring hospitalization) would be more common than previously reported. Methods: We created a retrospective cohort of 31,951 Veterans with AF aged ≥75 years who were new referrals to VA anticoagulation clinics (warfarin) from 1/1/02 - 12/31/12. Patients with comorbid conditions requiring warfarin (e.g. pulmonary embolus) were excluded. Data were extracted from the VA electronic medical record and linked with Medicare claims data for subsequent hospitalizations. The primary outcome was any hospitalization for bleeding. We identified bleeding subtypes by source, and compared characteristics of patients with and without bleeding hospitalizations. Results: Mean population age was 81.1 years, 98.1% were male, and 8.4% were nonwhite. Over a median follow-up period of 2.62 years, 7288 patients (22.8%) were hospitalized for bleeding. There were 12,004 total bleeding events; overall, 980 (13.4%) patients experienced multiple events. The most common bleeding sources (first event) were gastrointestinal (50.8%), genitourinary (21.6%), and intracranial (9.4%) (Figure). The median time to first bleeding event was 1.59 years. Patients hospitalized for bleeding were more likely to have coronary disease (48.4% vs. 40.9%, P<0.01); COPD (28.4% vs. 24.7%, P<0.01); chronic kidney disease (17.8% vs. 16.0%, P<0.01); CHF (34.7% vs. 29.5%, P<0.01), and labile INR (63.3% vs. 53.7%, P<0.01). The rate of hospitalization for stroke over the same time period was 5.0%. Conclusions: After initiating warfarin, over one in five older Veterans are hospitalized for bleeding, most commonly from a gastrointestinal source. Comorbidity burden and labile INR place these patients at increased risk.

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Hospitalization As a Risk Factor for Bleeding: The Medical Inpatients Thrombosis and Hemostasis (MITH) Study

Blood ◽

10.1182/blood-2021-151536 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1915-1915

Author(s):

Mansour Gergi ◽

Katherine Wilkinson ◽

Insu Koh ◽

Jordan Munger ◽

Hanny Al-Samkari ◽

...

Keyword(s):

Primary Care ◽

Predictive Value ◽

Research Funding ◽

Absolute Risk ◽

Bleeding Event ◽

Bleeding Risk ◽

Bleeding Events ◽

The Past ◽

Increased Risk ◽

Age And Sex

Abstract Introduction: Bleeding risk is understudied in recently discharged medical patients and often less appreciated than venous thrombosis risk. Knowledge of both absolute and relative bleeding risk in people recently discharged from medical hospitalizations is needed to balance the risks of thrombosis and bleeding. We therefore quantified the relative and absolute risk of bleeding requiring hospitalization in patients recently discharged (up to 3 months) after a bleeding-free medical admission. Methods: We followed all primary care patients aged ≥18 at the University of Vermont Medical Center's primary care clinics from July 2010 to September 2019, capturing all hospitalizations and bleeding events that followed these hospitalizations for 3 months after discharge. Using International Classification of Disease (ICD) 9 and 10 discharge diagnoses, laboratory values, current procedure terminology (CPT) codes and flowsheet data for transfusion support, we developed and validated computable phenotypes to identify bleeding events. Validation was performed manually by abstracting 150 charts with bleeding events detected by the phenotype and 40 charts without a bleeding event. Present on admission (POA)-bleeding was defined if bleeding occurred <24 hours after admission, and hospital-acquired (HA) if it occurred ≥24 hours after admission. For this analysis, our outcome was POA-bleeding. Bleeding risk was estimated using successive 1-month intervals after discharge as a time-varying covariate in age- and sex-adjusted Cox proportional hazard models. The reference group was bleeding risk in people with no hospitalization in the prior 3 months. HA-bleeding occurring within 3 months of a previous hospitalization were not grouped with the prior hospitalization. Results: From 2010-2019, among 67,571 people with a mean age of 48 years (56.7% female) followed for a median of 6.2 years, there were a total of 14,266 medical hospitalizations and 1,784 hospitalized bleeding events (568 HA and 1216 POA). The bleeding computable phenotype had a positive predictive value of 79% and a negative predictive value of >99%. The rate of bleeding in people with no hospitalizations within the past 3 months was 2.88 per 1000 person-years. Over the 1 month after discharge, the rate was 153.8 per 1000 person-years decreasing to 61 per 1000 person-years in the second month after discharge and 29 per 1000 person-years in the third month after discharge. The age- and sex-adjusted HR for bleeding was 26.9 the first month after discharged and decreased respectively to 15.3 and 8 over successive 1-month intervals after discharge, relative to those with no hospitalization in the past 3 months (Table). Conclusion: In this northern Vermont population, the three months after a medical hospitalization was associated with dramatically increased risk of hospitalization for bleeding compared to people with no recent hospitalizations. Findings demonstrate how common bleeding is after hospitalization and emphasize on the need to develop methods to quantify bleeding risk. Figure 1 Figure 1. Disclosures Al-Samkari: Novartis: Consultancy; Moderna: Consultancy; Argenx: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding.

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Incidence of Bleeding in Patients with Sickle Cell Disease: A Population Based Study

Blood ◽

10.1182/blood-2018-99-114223 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 10-10

Author(s):

Nisha Hariharan ◽

Ann M Brunson ◽

Theresa H.M. Keegan ◽

Ted Wun

Keyword(s):

Ischemic Stroke ◽

Cumulative Incidence ◽

Hemorrhagic Stroke ◽

Severe Disease ◽

Bleeding Event ◽

Gi Bleeding ◽

Gross Hematuria ◽

Bleeding Events ◽

Risk Of Death ◽

Increased Risk

Abstract Background: Bleeding in patients with sickle cell disease (SCD) occurs at a number of sites, often with significant morbidity and mortality. The increased risk of hemorrhagic stroke, hematuria, and vitreous hemorrhage in SCD patients is well known. However, the overall cumulative incidence of both major and clinically relevant, non-major bleeding events in SCD patients has not been well-described. Therefore, we determined the cumulative incidence of and risk factors for bleeding amongst patients with SCD. We also determined the association between bleeding and overall mortality. Methods: We utilized the California Patient Discharge Dataset (PDD) and Emergency Department (ED) Dataset to identify patients with SCD between 1991-2014. We then used specific ICD-9 CM codes to identify the first admission (PDD or ED) for bleeding events: intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, hemophthalmos, gross hematuria, and "other" bleeding (including hemopericardium, pulmonary bleed, and hemarthrosis). The cumulative incidence of bleeding was adjusted for the competing risk of death using age as the time scale and stratified by disease severity (severe disease was defined as requiring an average of ≥ 3 hospitalizations or ED visits per year). Cox proportional hazards regression models were used to determine factors associated with bleeding (all, ICH and GI) and the association of bleeding with mortality. Models included age, race, SCD related complications (ischemic stroke, venous thromboembolism [VTE], osteonecrosis of the femoral head [ONFH], renal failure, and liver failure) and disease severity. Complications and bleeding were included as time-dependent covariates. Results: Of the 6,423 SCD patients identified, 15.9% had an index bleeding event. Of these, 65.6% were GI bleeding, 14.2% were ICH, 7.1% were hemophthalmos, 4.3% were gross hematuria, and 8.8% were other types of bleeding. The top six diagnoses of GI bleeding were GI hemorrhage not otherwise specified, melena, hematemesis, rectal and anal hemorrhage, chronic gastric ulcer with hemorrhage, and Mallory-Weiss syndrome. Figure 1 shows the cumulative incidence of bleeding overall and by bleeding type. The incidence of all bleeding was 15.5% (95% confidence interval (CI) 14.4 - 16.6) at age 40 years and 33.6% (CI 31.5 - 35.8%) at age 60. The incidence of bleeding was higher among SCD patients with severe disease. For example, the cumulative incidence of GI bleeding at age 40 was 15.8% (CI 14.2-17.4%) among severe SCD patients compared to 4.8% (CI 3.9-5.8%) for those with less severe disease. In multivariable models, a higher risk of all bleeding was associated with severe SCD, VTE within 180 days prior to bleeding event, ONFH, ischemic stroke, renal failure and liver failure (Table 1). In multivariable models by bleeding type, there was a strong association between VTE and ischemic stroke with risk of ICH. In addition, ONFH was positively associated with risk of GI bleed. Bleeding was associated with a two-fold increased risk of death (hazard ratio =2.28; CI 1.97-2.64), adjusted for other SCD related complications. Bleeding had a similar negative effect on mortality as other complications. Conclusion: The findings from our study indicate that SCD patients have a high cumulative incidence of bleeding. While the increased incidence of intracranial, urological, and retinal bleeding has been previously described and are confirmed here, we present the novel finding that SCD patients also have a high incidence of GI bleeding, the majority of which are from an upper GI source. The association of hemorrhagic stroke with a history of ischemic stroke is also confirmed. The association of bleeding with VTE is likely due, at least in part, to anticoagulation. Further studies on the causes and risk factors for GI bleeding in patients with SCD are warranted, and possibilities include gastritis from increased use of non-steroidal anti-inflammatory drugs (hence the association of ONFH with GI bleeding) and stress ulcerations from frequent hospitalizations. Such data could inform preventive strategies. Disclosures No relevant conflicts of interest to declare.

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