The Impact of Different Prophylactic Anticoagulation Doses on the Outcomes of Patients with COVID-19

Introduction As the COVID-19 pandemic spread throughout the world, it was seen that patients who presented with critical disease had a higher incidence of thrombotic complications, associated with a poor prognosis. Currently prophylactic anticoagulation is recommended for all patients with COVID-19 who require hospitalization as part of the supportive management. However, since a higher incidence of thrombosis despite prophylactic anticoagulation has been reported, some recommendations indicate that an increase to intermediate or therapeutic dosing should be considered. The full spectrum of complications and outcomes related to this strategy are still unknown. Methods We conducted a cross-sectional study using the COVID-19 registry of the ARMII study group, based in Centro Medico ABC, a private hospital in Mexico City. We included all patients admitted from March 12 to July 31, 2020, who received prophylactic anticoagulation at standard (enoxaparin 40mg QD), intermediate (0.5 mg/kg QD or 40 mg BID), or therapeutic doses (1mg/kg BID), a decision taken by the attending physician based on clinical and laboratory criteria. Patients with previous or presenting with thrombosis were excluded. We compared the three groups to identify baseline characteristics and conducted multivariable logistic regressions to measure the association of anticoagulation profiles and adverse outcomes. Results Out of total 322 patients, we identified 81 (25%) who received standard dose, 164 (51%) who received intermediate and 77 (24%) on therapeutic doses. Age and sex were distribuited similarly among groups; patients with intermediate and therapeutic doses were more overweight and obese, but this was not significant (p=0.052). On admission, patients who received intermediate and therapeutic doses had lower oximetry registry when compared with standard doses (89%, 88% and 92% respectively, p=0.008). Three severity scales, NEWS, MULBSTA and CALL, were higher in patients with intermediate and therapeutic doses (p=0.01, p=0.02 and p=0.005, respectively). Regarding laboratory values, patients on therapeutic doses had higher leucocytes on admission (median 6 x 109L, 6 and 8, p=0.05) but lower lymphocyte absolute counts (median 1240 cells/mm3, 935 and 920, p<0.001). Patients who were given higher doses of anticoagulation had higher levels of C-reactive protein, DHL, and ferritin (p<0.001) and higher levels of IL-6 (p=0.02). Levels of D-dimer were also higher in this group (p<0.001). Patients with therapeutic doses of anticoagulation were more likely to present major bleeding when compared to intermediate or standard prophylactic doses (9% vs 1% vs 0%, p=0.0006) and clinically relevant bleeding (12% vs 2% vs 5%, p=0.01). (Table 1) The incidence of pulmonary embolism (PE) in the entire cohort was 5%, while the incidence of major bleeding was 2.5%. There were no differences between the different doses of anticoagulation; no patients presented deep venous thrombosis. During follow-up, a total of 21 patients died, representing 6.5% of the study population. Independent factors that predicted death included age, CRP and D-dimer levels on admission, history of hypertension and requirement of mechanical invasive ventilation. When adjusting for these confounders, therapeutic anticoagulation was associated with a lower risk of death (OR 0.079 95% CI 0.008-0.76). When restricting the analysis for patients who required mechanical ventilation, anticoagulation was also associated with a lower risk of death (OR 0.031 95% CI 0.002-0.54) but not for intermediate doses (OR 0.10 95% CI 0.01-1.06). (Figure 1) Conclusions Anticoagulation might not play a causal role in the risk of requiring mechanical ventilation, but the decision to increase doses might reflect patients who present with more severe disease. In our cohort, the majority of the patients were receiving intermediate prophylactic doses and the incidence of PE is lower than in worldwide reports. Therapeutic doses of anticoagulation were not associated with a lower risk of PE, but were associated with lower risk of death. However, therapeutic doses were also associated with a higher risk of major and clinically significant bleeding. Randomized-controlled clinical trials are needed to understand the role of higher doses of prophylactic anticoagulation in COVID-19. Disclosures No relevant conflicts of interest to declare.

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Increasing Doses of Anticoagulation Are Associated with Improved Survival in Hospitalized COVID-19 Patients

Blood ◽

10.1182/blood-2020-134835 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-22

Author(s):

Filip Ionescu ◽

Girish B Nair ◽

Ioana Petrescu ◽

Anish S Konde ◽

Markie Sue Zimmer ◽

...

Keyword(s):

Major Bleeding ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Conflicts Of Interest ◽

Hazard Ratio ◽

Red Blood Cell Transfusion ◽

Packed Red Blood Cells ◽

Risk Of Death ◽

Hazards Model ◽

Higher Doses

Background: Hypercoagulability may contribute to COVID-19 pathogenicity. Evidence comparing clinical outcomes among patients with COVID-19 receiving therapeutic compared to prophylactic dose anticoagulation is limited. We evaluated whether therapeutic anticoagulation (tAC) is associated with improved survival compared to prophylactic (pAC) and no anticoagulation (AC) in hospitalized COVID-19 patients. Methods: This was a retrospective, multi-center cohort study of consecutive COVID-19 patients admitted between March 13th, 2020 and May 5th, 2020 to eight hospitals within a large academic system in Southeast Michigan, USA. Participants were assigned to three groups based on whether they received no AC, pAC throughout most of their hospitalization, or at least 3 days of tAC. Major bleeding was defined as transfusion of five or more units of packed red blood cells within 48 hours regardless of hemoglobin level, hemoglobin < 7g/dL and any red blood cell transfusion or a diagnosis code for major bleeding during the hospitalization or radiological evidence of intracranial hemorrhage Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n=642) were treated in the intensive care unit (ICU). 60.9% received pAC (n=2121), 28.7% received at least 3 days of tAC (n=998), and 10.4% (n=361) did not receive AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated a statistical difference in the 25-day survival probability in the tAC group compared to the pAC group (57.5% vs 50.7%, Figure). In a PS weighted multivariate proportional hazards model adjusting for age, body mass index and ICU status, AC was associated with a reduced risk of death at both prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently among tAC patients (81 [8.1%]) compared to those who received no AC (20 [5.5%]) or pAC (46 [2.2%]). Conclusions : Higher doses of AC are associated with lower mortality in hospitalized COVID-19 patients. The lowest hazard ratio was observed in ICU patients, but risk was also significantly lower in non-ICU hospitalized patients. Bleeding occurred more frequently with higher doses of anticoagulation. Ongoing randomized trials are warranted to prospectively evaluate efficacy and risk of tAC in patients with COVID-19. Figure Disclosures No relevant conflicts of interest to declare.

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Therapeutic Anticoagulation Delays Death in COVID-19 Patients: Cross-Sectional Analysis of a Prospective Cohort

TH Open ◽

10.1055/s-0040-1716721 ◽

2020 ◽

Vol 04 (03) ◽

pp. e263-e270 ◽

Cited By ~ 2

Author(s):

Filip Ionescu ◽

Giovi Grasso-Knight ◽

Edward Castillo ◽

Ehsun Naeem ◽

Ioana Petrescu ◽

...

Keyword(s):

Dependent Manner ◽

Cross Sectional ◽

Time To Death ◽

Cross Sectional Analysis ◽

Therapeutic Anticoagulation ◽

Prophylactic Anticoagulation ◽

Therapeutic Doses ◽

Sectional Analysis ◽

The Impact ◽

Higher Doses

AbstractA hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC (n = 67), pAC (n = 47), and no AC (n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.

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Survival in elderly glioblastoma patients treated with bevacizumab-based regimens in the United States

Neuro-Oncology Practice ◽

10.1093/nop/npy001 ◽

2018 ◽

Vol 5 (4) ◽

pp. 251-261 ◽

Cited By ~ 2

Author(s):

Jessica Davies ◽

Irmarie Reyes-Rivera ◽

Thirupathi Pattipaka ◽

Stephen Skirboll ◽

Beatrice Ugiliweneza ◽

...

Keyword(s):

Elderly Patients ◽

Lower Risk ◽

Karnofsky Performance Status ◽

The United States ◽

Cox Proportional Hazards Model ◽

Sensitivity Analyses ◽

Primary Analysis ◽

Risk Of Death ◽

Initial Surgery ◽

The Impact

AbstractBackgroundThe efficacy of bevacizumab (BEV) in elderly patients with glioblastoma remains unclear. We evaluated the effect of BEV on survival in this patient population using the Survival, Epidemiology, and End Results (SEER)-Medicare database.MethodsThis retrospective, cohort study analyzed SEER-Medicare data for patients (aged ≥66 years) diagnosed with glioblastoma from 2006 to 2011. Two cohorts were constructed: one comprised patients who had received BEV (BEV cohort); the other comprised patients who had received any anticancer treatment other than BEV (NBEV cohort). The primary analysis used a multivariate Cox proportional hazards model to compare overall survival in the BEV and NBEV cohorts with initiation of BEV as a time-dependent variable, adjusting for potential confounders (age, gender, Charlson comorbidity index, region, race, radiotherapy after initial surgery, and diagnosis of coronary artery disease). Sensitivity analyses were conducted using landmark survival, propensity score modeling, and the impact of poor Karnofsky Performance Status.ResultsWe identified 2603 patients (BEV, n = 597; NBEV, n = 2006). In the BEV cohort, most patients were Caucasian males and were younger with fewer comorbidities and more initial resections. In the primary analysis, the BEV cohort showed a lower risk of death compared with the NBEV cohort (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89; P < .01). The survival benefit of BEV appeared independent of the number of temozolomide cycles or frontline treatment with radiotherapy and temozolomide.ConclusionBEV exposure was associated with a lower risk of death, providing evidence that there might be a potential benefit of BEV in elderly patients with glioblastoma.

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Abstract MP35: The American Heart Association’s Life’s Simple 7 and Mortality by Race and Sex in the U.S.: the REasons for Geographic And Racial Differences in Stroke (REGARDS) Cohort

Circulation ◽

10.1161/circ.129.suppl_1.mp35 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Mary Cushman ◽

Suzanne E Judd ◽

Virginia J Howard ◽

Neil A Zakai ◽

Brett Kissela ◽

...

Keyword(s):

Racial Differences ◽

Mortality Risk ◽

Lower Risk ◽

Population Sample ◽

White Men ◽

The United States ◽

Risk Of Death ◽

Life’S Simple 7 ◽

Life's Simple 7 ◽

The Impact

Background: The Life’s Simple 7 (LSS) metric is being used by AHA to track the cardiovascular health of the United States population and move toward a 2020 impact goal for improvement. Levels of LSS are associated with mortality risk but there are limited data on whether this association differs by race or sex. Hypothesis: There will be sex and race differences in the association of LSS with mortality in the REGARDS cohort study. Methods: We studied 29,692 REGARDS participants; a population sample of black and white men and women aged 45-98 from across the US, enrolled in 2003-7. Extensive baseline risk factor data were measured in participants’ homes. The 7 LSS components (blood pressure, cholesterol, glucose, body-mass index, smoking, physical activity, diet) were each scored in AHA-defined categories of poor (0 points), intermediate (1 point) and ideal (2 points), and were summed to yield scores ranging from poor for all (0) to ideal for all (14). With 6.4 years follow up there were 3709 deaths. Results: The LSS score was normally distributed with mean (SD) of 7.9 (2.0) in whites and 6.9 (2.0) in blacks. The age, region, income and education adjusted hazard ratio (HR) of death for a 1-unit worse LSS score, stratified by race and sex, are shown in the table. Race and sex interactions were tested individually in separate models. While better scores for LSS were strongly associated with lower mortality, associations differed by race and sex, being weaker in blacks than whites and in men than women. Conclusion: There were large associations of LSS with mortality risk in the REGARDS national sample; 1 point difference in score, corresponding to movement from poor to intermediate or intermediate to ideal for 1 of the 7 factors, was associated with a 16% lower risk of death in white women, 14% lower risk in white men or black women, but only an 11% lower risk in black men. Observed differences in the association of LSS with mortality by race and sex should be considered in efforts to gauge the impact of LSS interventions on health disparities.

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Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽

10.1136/bmj.m2980 ◽

2020 ◽

pp. m2980 ◽

Cited By ~ 49

Author(s):

Reed AC Siemieniuk ◽

Jessica J Bartoszko ◽

Long Ge ◽

Dena Zeraatkar ◽

Ariel Izcovich ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Standard Care ◽

Interferon Beta ◽

Meta Analysis ◽

Risk Of Bias ◽

Drug Discontinuation ◽

Duration Of Symptoms ◽

Risk Of Death ◽

The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

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Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance

Open Heart ◽

10.1136/openhrt-2021-001619 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001619

Author(s):

Gema Miñana ◽

Julio Núñez ◽

Jose V Monmeneu ◽

Maria P López-Lereu ◽

Jose Gavara ◽

...

Keyword(s):

Cardiovascular Magnetic Resonance ◽

Magnetic Resonance ◽

Lower Risk ◽

Potential Effect ◽

Vasodilator Stress ◽

P Value ◽

Risk Of Death ◽

Coronary Syndrome ◽

The Impact ◽

Stress Cardiovascular Magnetic Resonance

ObjectiveWe assessed the influence of the ischaemic burden (IB) as derived from vasodilator stress cardiovascular magnetic resonance (CMR) on the risk of death and the effect of revascularisation across sex.MethodsWe evaluated 6237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischaemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used.ResultsA total of 2371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularisation. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived IB across sex (p value for interaction=0.039). Women exhibited an adjusted lower risk of death and only equaled men’s risk when extensive ischaemia was present. Likewise, CMR-related revascularisation was shown to be differentially associated with the risk of mortality across sex (p value for interaction=0.025). In patients with non-extensive ischaemia, revascularisation was associated with a higher risk of death, with a greater extent in women. At higher IB, revascularisation was associated with a lower risk in men, with more uncertain results in women.ConclusionsCMR-derived IB allows predicting the risk of death and gives insight into the potential effect of revascularisation in men and women with CCS. Compared with men, women with non-extensive ischaemia displayed a lower risk and a similar risk with a higher IB. The impact of CMR-related revascularisation on mortality risk was also significantly different according to IB and sex. Further research will be needed to confirm these hypothesis-generating findings.

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Graft-Versus-Leukemia (GVL) Effect After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Treatment for Acute Myeloid Leukemia (AML): a Survey From the Acute Leukemia Working Party of the EBMT.

Blood ◽

10.1182/blood.v114.22.3313.3313 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3313-3313

Author(s):

Frederic Baron ◽

Myriam Labopin ◽

Mohamad Mohty ◽

Nadezda Basara ◽

Dietger Niederwieser ◽

...

Keyword(s):

High Risk ◽

Lower Risk ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Working Party ◽

Cox Models ◽

Landmark Analysis ◽

Factors Associated ◽

The Impact ◽

Risk Of Relapse

Abstract Abstract 3313 Poster Board III-201 RIC allo-SCT has been increasingly used as treatment for AML patients (pts) ineligible for myeloablative allo-SCT. Previous studies have observed a lower risk of relapse in pts who experienced chronic GVHD after RIC allo-SCT versus in those who did not. The objective of the current study was to further investigate the association between chronic GVHD and relapse in a large cohort of pts given RIC allo-SCT as treatment for AML. Data from 1188 AML pts in first or second CR transplanted between 2000 and 2008 following a RIC regimen at EBMT affiliated centers were analyzed. Patients were given PBSC from HLA-identical sibling (MRD, n=879), or from HLA-matched unrelated donors (MUD, n=309). RIC was defined as Busulfan conditioning regimens containing ≤ 8mg/kg total dose, or TBI <6 Gy. Median pt age at transplantation was 55 (range, 18-76) yrs in pts given grafts from MRD, versus 57 (range, 19-72) yrs in those given grafts from MUD. 54 pts had good risk (4.5%), 564 standard-risk (47.5%), and 116 high-risk (9.8%) cytogenetics, while cytogenetic was unknown in 454 pts (38.2%). The impact of chronic GVHD on relapse risk, non-relapse mortality (NRM) and leukemia-free survival (LFS) was assessed by time-dependent multivariate Cox models and in a landmark analysis. Three-yr incidences of relapse, NRM and LFS were 35 ± 2%, 14 ± 2%, and 50 ± 2%, respectively, while 2-yr incidence of chronic GVHD was 49 ± 2%. In a landmark analysis at 18 months after allo-SCT, 5-year relapse rates were 10 ± 2% versus 19 ± 3% for patients with or without chronic GVHD (P=0.04), respectively. In multivariate Cox models, CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.008), alemtuzumab use in the RIC (P=.048), TBI-based RIC (P=.006), high-risk cytogenetics (P=.001), and absence of chronic GVHD (P=.015) were each associated with higher risk of relapse. Factors associated with high NRM were MUD versus MRD (P=.003), grade II-IV acute GVHD (P<.001), and chronic GVHD (P=.002). Factors associated with lower LFS were CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.007), alemtuzumab use in the RIC (P=.012), and high-risk cytogenetics (P=.003). In conclusion, in this cohort of AML patients transplanted in remission, chronic GVHD was associated with a lower risk of relapse while profound in-vivo T cell depletion with alemtuzumab was associated with higher relapse rate suggesting that GVL effects play a role in preventing AML relapse in patients given RIC allo-SCT. Therefore, closed surveillance of patients in this setting not presenting chronic GVHD such as decreasing of immunosuppression should be further investigated. Disclosures No relevant conflicts of interest to declare.

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Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry

Blood ◽

10.1182/blood.v126.23.1677.1677 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1677-1677

Author(s):

Louise De Swart ◽

Tom Johnston ◽

Alexandra Smith ◽

Pierre Fenaux ◽

Argiris Symeonidis ◽

...

Keyword(s):

Lower Risk ◽

Research Funding ◽

Control Group ◽

Rapid Decline ◽

Prognostic Impact ◽

Platelet Counts ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival. Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up. Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p<0.001). The risk of death was increased in the intermediate IPSS-R risk group compared to low risk. Patients with RARS and 5q- syndrome had a better outcome compared to RCMD. Increased RBCT intensity in 1yrPD (Table, Figure) was strongly associated with an increased risk of death (p<0.001). In the 1660 patients no significant decline in platelet counts was observed (0.16x109 platelets/l average monthly decline, p=0.16) among patients who were not RBC transfused at any time during follow-up. However platelet counts of patients receiving RBCT declined more quickly (p<0.0001) at an average rate of 1.14x109 platelets/l/month. Among the 920 RBCT dependent patients, lower platelet counts were associated with receiving more RBCT units in the preceding six months. 185 Patients had at least 2 observations both before and after becoming RBCT dependent, defined as 1st RBCT. 50% of these patients had a decreasing trend of platelets prior to their 1st RBCT and 67% had a decreasing slope of platelets after their 1st RBCT. In the control group of RBC untransfused patients, decreasing slopes of platelets occurred in around 50% of the patients throughout the whole observation period of 4 visits. Logistic regression of the risk of having a post-1st RBCT decreasing trend in platelets showed that transfused patients were at a greater risk (OR=1.7, 95% CI: 1.1-2.7) of having a post-1st RBCT decreasing trend in platelets than untransfused patients. Conclusion These multivariate regression models including age, sex, country, IPSS and WHO classification showed that more intensive RBCT treatment is associated with poor prognosis and a more rapid decline of platelets. This indicates that the intensity of RBCT should be incorporated in the regular prognostic scoring systems and the choice of therapeutic interventions. (1): De Swart L et al. Br J Haematol 2015; 170: 372-83. Disclosures Fenaux: NOVARTIS: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding. Hellström-Lindberg:Celgene Corporation: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau. Mittelman:Roche: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Research Funding. Almeida:Bristol Meyer Squibb: Speakers Bureau; Shire: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Itzykson:Oncoethix: Research Funding. de Witte:Novartis: Research Funding.

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Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Blood ◽

10.1182/blood-2021-154088 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1960-1960

Author(s):

Azza Ahmed ◽

Ahmed Pasha ◽

David O. Hodge ◽

Ana I Casanegra ◽

Lisa Peterson ◽

...

Keyword(s):

Major Bleeding ◽

Low Dose ◽

Conflicts Of Interest ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Venous Thromboembolic Event ◽

Low Doses ◽

Cox Models ◽

Therapeutic Anticoagulation ◽

Therapeutic Doses

Abstract Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown. Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis. Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02). Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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SUN-620 Gender Difference in the Outcome of Patients with Diabetes Admitted for Hyperosmolar Hyperglycemia. from the National Inpatient Sample

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1048 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Fatima Ahmed ◽

Ashraf Abugroun ◽

Manar Elhassan ◽

Berhane Seyoum

Keyword(s):

Mechanical Ventilation ◽

Length Of Stay ◽

Lower Risk ◽

Female Gender ◽

Secondary Outcome ◽

National Inpatient Sample ◽

Patients With Diabetes ◽

Hyperosmolar Hyperglycemic State ◽

The Mean ◽

The Impact

Abstract Objective: There is paucity of literature on the impact of gender on outcomes of hyperosmolar hyperglycemic state (HHS) among adult patients with diabetes. The aim of this study was to evaluate the effect of gender on the outcome of these patients. Methodology: The National Inpatient Sample (NIS) was queried for all patients who were admitted with a diagnosis of hyperosmolar hyperglycemic state (HHS) during the years 2005-2014. The primary outcomes of the study were all-cause mortality, acute myocardial infarction (MI), and acute stroke. The secondary outcomes were acute kidney injury (AKI), rhabdomyolysis, acute respiratory failure (ARF), need for mechanical ventilation (MV), length of stay (LOS), and total cost of stay. Results: Overall, 188,725 patients were admitted for HHS. Mean age of males was 53.7, standard error of the mean (SEM: 0.13), and of females was 58.5 (SEM: 0.15), p<0.001. Females were (43.9%), Caucasians were 37.4% while African Americans were 35.2%. Total mortality was 1.1%, MI was 1.3% and stroke was 1.1%. Most common secondary outcome was AKI seen in 31.3% followed by ARF seen in 2.9% of total. The mean cost was 7887 $ (SEM: 84.6) and mean LOS was 4.1 days (SEM: 0.03). Both males and females had equivalent rates of mortality, stroke, ARF and need for mechanical ventilation. Compared to males, females had significantly higher risk for MI 1.6% vs 1.1%, p<0.001, lower risk for AKI 29.3% vs 32.9%, p<0.001, lower risk for rhabdomyolysis 1.1% vs 2%, p<0.001 and higher LOS 4.3 vs 3.9 days, p<0..01 and higher total costs 8165.6 $ vs 7669.3 $, p < 0.001. On multivariable analysis, female gender was independently predictive for higher risk for MI with adjusted odds ratio (aOR) 1.34 [95%CI: 1.08-1.67] p=0.01 and lower risk for rhabdomyolysis with aOR 0.52 [95%CI: 0.42-0.63] p<0.001 and lower risk for AKI with aOR 0.74 [95%CI: 0.7-0.78] p<0.001. In addition, female gender correlated with higher cost and length of stay. Conclusion: Females with hyperosmolar hyperglycemic state are at higher risk for MI and lower risk for AKI and rhabdomyolysis.

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