Observational study of thrombosis and bleeding in COVID-19 VV ECMO patients

Introduction: COVID-19 has been associated with increased risk of thrombosis, heparin resistance and coagulopathy in critically ill patients admitted to intensive care. We report the incidence of thrombotic and bleeding events in a single center cohort of 30 consecutive patients with COVID-19 supported by veno-venous extracorporeal oxygenation (ECMO) and who had a whole body Computed Tomography Scanner (CT) on admission. Methodology: All patients were initially admitted to other hospitals and later assessed and retrieved by our ECMO team. ECMO was initiated in the referral center and all patients admitted through our CT scan before settling in our intensive care unit. Clinical management was guided by our institutional ECMO guidelines, established since 2011 and applied to at least 40 patients every year. Results: We diagnosed a thrombotic event in 13 patients on the initial CT scan. Two of these 13 patients subsequently developed further thrombotic complications. Five of those 13 patients had a subsequent clinically significant major bleeding. In addition, two patients presented with isolated intracranial bleeds. Of the 11 patients who did not have baseline thrombotic events, one had a subsequent oropharyngeal hemorrhage. When analyzed by ROC analysis, the area under the curve for % time in intended anticoagulation range did not predict thrombosis or bleeding during the ECMO run (0.36 (95% CI 0.10–0.62); and 0.51 (95% CI 0.25–0.78); respectively). Conclusion: We observed a high prevalence of VTE and a significant number of hemorrhages in these severely ill patients with COVID-19 requiring veno-venous ECMO support.

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The effectiveness and safety of the use of antithrombotic therapy in COVID-19

Ambulatornaya khirurgiya = Ambulatory Surgery (Russia) ◽

10.21518/1995-1477-2021-18-2 ◽

2021 ◽

Vol 18 (2) ◽

pp. 17-30

Author(s):

K. V. Lobastov ◽

O. Ya. Porembskay ◽

I. V. Schastlivtsev

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Increased Risk ◽

Severe Infections ◽

Thrombotic Complications ◽

Risk Of Disease ◽

Anticoagulant Prophylaxis ◽

Discharge From Hospital ◽

Outpatient Settings

The article is a non-systematic review of the literature, addressing the effectiveness, safety and appropriateness of antithrombotic drugs for COVID-19 in patients undergoing treatment in different settings: in the hospital phase, including the intensive care unit, in the outpatient phase after discharge from hospital, in primary outpatient treatment. The issues of thrombotic complications during vaccination and the necessity of their prevention are discussed. The studies confirm the importance of prophylactic doses of anticoagulants in all hospitalized patients. The use of increased doses has proven ineffective in patients with a severe course of the disease who are being treated in the intensive care unit. In moderately severe infections, there is a clear benefit of increased doses of anticoagulants in reducing the risk of organ failure, but definitive conclusions can only be drawn after the final results of the studies have been published. Prolonged pharmacological prophylaxis after hospital discharge may be useful in individual patients, but the overall risk of thrombotic complications in the long-term period does not appear to be high. The available data do not support the use of anticoagulants in the treatment of coronavirus disease in the outpatient settings, since the risk of thrombotic complications is not increased in such patients, and the safety of anticoagulant use has not been evaluated. Sulodexide may be useful in selected outpatients at increased risk of disease progression. Vaccination may provoke the development of atypical localized thrombosis by immune mechanisms, but the risk of such complications is lower in the coronavirus disease itself. Anticoagulant prophylaxis during vaccine administration is not indicated.

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Is PI-RADS 3/total lesion ratio associated with clinically-significant prostate cancer in patients with equivocal-risk lesions on multi-parametric MRI?

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.149 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 149-149

Author(s):

Kamyar Ghabili ◽

Matthew Swallow ◽

Alfredo Suarez-Sarmiento ◽

Jamil Syed ◽

Michael Leapman ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Volume ◽

Area Under The Curve ◽

Lesion Volume ◽

Fusion Biopsy ◽

Grade Group ◽

Psa Density ◽

Increased Risk ◽

Positive Core ◽

Clinically Significant

149 Background: Prostate imaging reporting and data system (PI-RADS) category 3 (P3) provides an equivocal assessment of prostate cancer (PCa). We aimed to investigate imaging parameters including the ratio of P3-to-total regions of interest (ROI) that may assist in identifying P3 lesions harboring clinically-significant PCa (csPCa). Methods: We retrospectively queried our institutional MRI-ultrasound fusion biopsy database to identify patients without a prior diagnosis of PCa and with at least one P3 lesion on multi-parametric MRI (mpMRI) who underwent fusion biopsy during Feb 2015-Oct 2017. mpMRI findings were assessed, including prostate and P3 volumes, number of ROIs, and P3-to-total ROIs ratio (P3 lesion volume/total ROIs volumes). Logistic regression and area under the curve (AUC) were used to assess the ability of clinical and mpMRI characteristics to predict csPCa, defined as any grade group (GG)≥2 cancer or GG 1 cancer in > 2 cores or > 50% of any positive core from targeted biopsy of the P3 lesion. Results: Of 127 men with at least one P3 lesion, 29 (22.8%) had csPCa on the biopsy of P3 lesions. Patients with csPCa in P3 lesions had smaller prostate volumes (42.1mL vs 56mL, p = 0.003), lower P3/total ROIs ratios (0.46 vs 1.00, p < 0.001), and higher numbers of total ROIs (2 vs 1, p = 0.004). Compared with patients who had a P3/total ROIs ratio > 0.58, men with ratios < 0.58 were more likely to be diagnosed with csPCa in a P3 lesion (57.1% vs 9%, p < 0.001). Using a threshold of 0.58, P3/total ROIs ratio was 76.1% sensitive and 80.6% specific for csPCa in a P3 lesion. On multivariate analysis, smaller prostate volume (OR1.04, 95%CI 1.01-1.07, p = 0.01) and lower P3/total ROIs ratio (OR1.04, 95%CI 1.02-1.07, p = 0.003) were associated with an increased risk of csPCa in P3 lesions. P3/total ROIs ratio (AUC 0.73) and prostate volume (AUC 0.70) were superior to PSA density (AUC 0.65) for the prediction of csPCa in P3 lesions. Conclusions: Our data indicated that prostate volume and P3/total ROIs ratio outperformed PSA density in and were associated with detecting csPCa in P3 lesions. P3/total ROIs ratio could be used to avoid 80.6% of unnecessary biopsies of a P3 lesion in men with multiple ROIs.

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Staphylococcus pettenkoferi Bacteremia in an American Intensive Care Unit

Case Reports in Infectious Diseases ◽

10.1155/2021/5235691 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Cameron Strong ◽

Michael Cosiano ◽

Melanie Cabezas ◽

J. W. Barwatt ◽

L. Gayani Tillekeratne

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Case Reports ◽

Bloodstream Infections ◽

Signs And Symptoms ◽

The United States ◽

Coagulase Negative Staphylococci ◽

Prosthetic Devices ◽

Increased Risk ◽

Clinically Significant

Coagulase-negative staphylococci (CoNS) are considered the most common cause of nosocomial bloodstream infections; yet, these species are frequently designated as contaminants in the absence of systemic signs and symptoms of infection. Immunocompromised patients or those with prosthetic devices are at increased risk for clinically significant bacteremia. With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in clinical practice, there has been improved specificity of CoNS isolate identification and further elucidation of underrecognized pathogenic species. Staphylococcus pettenkoferi was a novel CoNS species first identified in 2002 and thought to be misdiagnosed as other CoNS due to limitations in biochemical identification. There is increasing identification of S. pettenkoferi isolates; however, there are limited case reports of clinically significant S. pettenkoferi bacteremia and no reported cases within the United States. We present the first known case of S. pettenkoferi from an American intensive care unit.

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A 10 Year Retrospective Analysis of Carotid Stenosis in Patients with Polycythemia Vera or Essential Thrombocythemia

Blood ◽

10.1182/blood.v124.21.5554.5554 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5554-5554

Author(s):

Arun Nagarajan ◽

Rahul Lanka ◽

Aravinda Nanjundappa ◽

Stephanie Thompson

Keyword(s):

Carotid Stenosis ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Conflicts Of Interest ◽

Thrombotic Event ◽

Tertiary Care ◽

Cell Counts ◽

Increased Risk ◽

Stenosis Severity ◽

Clinically Significant

Abstract Patients with polycythemia vera (PV) or essential thrombocythemia (ET) are at an increased risk for thrombotic events. The pathophysiology of hyperviscosity, leukocyte-induced endothelial damage, and the over-expression of JAK2 and STAT5 genes contributing to the development of atherothrombosis is poorly understood. As such, the goal of our study was to retrospectively examine carotid stenosis severity in patients with PV or ET and to determine if carotid stenosis is associated with thrombotic events in this patient group. We examined patients in a ten year period (2004 to 2014) who were under the care of a hematologist at our tertiary care-teaching hospital for either PV or ET, and, having one or more carotid duplex. Patients having diagnoses of secondary polycythemia or secondary thrombocytosis were excluded. Data obtained from patient charts included demographics, cardiovascular risk factors, thrombotic events, platelet and hematocrit levels, medications, and carotid stenosis severity. Clinically significant carotid stenosis was defined as >50 % stenosis. We compared patients with carotid stenosis to those without stenosis using Fisher exact tests. Of the 31 patients meeting study inclusion, only 9 (29%) presented with clinically significant carotid stenosis with 1 (3%) patient having increasing carotid stenosis severity during the study period. Elevated cell counts did not correlate with carotid stenosis. Elevated hematocrit levels of >45% or elevated platelet counts >400x 109/L, had no stasticial difference in the incidence of carotid stenosis versus no stenosis (50% vs. 18%, P = 0.16) and (63% vs. 64%, P = 1.00) respectively. There was no difference between the two groups with the use of either anti-platelet therapy (P = 0.68) or cytoreduction medications (P = 1.00) at the time of duplex. A total of 21 patients had 1 or more thrombotic event during the 10 year period. A total 35 thrombotic events occurred, with the distribution of events being 29% deep venous thrombosis, 28% stroke, 23% transient ischemia attack (TIA), 11% myocardial infarction, 3% peripheral arterial thrombosis, 3% pulmonary embolism and 3% retinal artery or vein occlusion. Rates of thrombotic events were comparable between ET and PV patients, with 10 of 15 patients with PV, 10 of 15 patients with ET and 1 patient with ET + PV experiencing a thrombotic event (P = 0.75). Carotid stenosis did not associate with increased rates of stroke or other thrombotic events. Stroke/TIA after duplex occurred in 22% of patients with carotid stenosis versus 9% of patients with no carotid stenosis (P = 0.56). Likewise, the rate of all thrombotic events after duplex was similar in patients with and without carotid stenosis (33% and 41%, respectively, P = 1.00). Two patients received carotid revascularization during the study period. Carotid endarterectomy appeared to be successful in one asymptomatic patient who presented with severe bilateral internal carotid artery stenosis. The other patient who received angioplasty for fibromuscular dysplasia and found to have carotid stenosis of <30% stenosis, later required neurological consults months post procedure due to TIA like symptoms. Thus, in this patient’s case, the underlying cause of the recurring symptoms may have been related to ET. This preliminarily study suggests that carotid stenosis may not predict thrombotic events in patients with ET or PV. Furthermore, patients with suspected carotid stenosis and/or presenting with stroke and having sustained elevated platelet/hematocrit levels may need to be evaluated for an underlying hematological disorder. Disclosures No relevant conflicts of interest to declare.

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Rates of Thrombotic Events in Hypereosinophilic Syndrome and the Effect of Molecular Aberrations in Thrombotic Risk

Blood ◽

10.1182/blood-2020-137311 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-14

Author(s):

Orly Leiva ◽

Olesya Baker ◽

Andrew M. Brunner ◽

Hanny Al-Samkari ◽

Rebecca Karp Leaf ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Hypereosinophilic Syndrome ◽

Thrombotic Event ◽

Advisory Committees ◽

Thrombotic Risk ◽

Risk Of Death ◽

Increased Risk ◽

Thrombotic Complications ◽

Molecular Aberrations

Background: Idiopathic hypereosinophilia and hypereosinophilic syndrome (HES) comprise a rare, heterogeneous group of hematologic disorders characterized by the overproduction of eosinophils leading to tissue eosinophilic infiltration and damage. Hypereosinophilia can be primary - due to a clonal or malignant process - or secondary to a non-clonal process. Primary eosinophilia can be accompanied by clonal markers, such as in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA/B, FGFR1 or PCM1-JAK2, genetic mutations or chromosomal abnormalities leading to a diagnosis of chronic eosinophilic leukemia. Without easily identifiable clonal markers, a diagnosis of idiopathic HES is made after secondary causes are excluded. Thrombotic complications in clonal eosinophilic disorders have been described in case reports but the prevalence of thrombosis has not been extensively studied. We hypothesized that HES is associated with an increased thrombotic risk compared to the general population. Additionally, given the known increased thrombotic risk in patients with clonal hematopoiesis of indeterminate potential, we also hypothesized that the risk of thrombosis is greatest in HES patients with evidence of an underlying clonal process. Methods: Using an institutional database, we retrospectively analyzed 44 patients with HES who had undergone molecular testing with a DNA based next generation sequencing (NGS) assay (Heme SnapShot) and an RNA based NGS assay (Heme fusion) as part of their work up for HES at Massachusetts General Hospital from 2016 to 2020. Patients with secondary eosinophilia were excluded. We used Fisher's exact test to compare rates of thrombotic events or death between patients with and without molecular aberration. Relative risk and corresponding 95% CI was estimated by fitting a log-binomial regression model. Results: Among the 44 patients analyzed, 16 (36.4%) had a molecular aberration detected on NGS. Of the patients with molecular aberrations detected, 4 (25%) had PGFRA, PGFRB, or FGFR1 fusions. Other pathogenic mutations were as follows - 1 (6.3%) JAK2 mutation, 3 (18.8%) TET2, 1 (6.3%) DNMT3A and 9 (56.4%) had mutations in other genes. White blood cell count, absolute eosinophil count, hematocrit, platelet count, tryptase and vitamin B12 levels at diagnosis of HES were similar between the two groups. After a median follow-up time of 29 months (IQR 19.3, 52), 9 (20.5%) of all HES patients had a thrombotic event after diagnosis of HES (4 venous and 5 arterial) with a median time to first thrombotic event of 14.0 months (IQR 3.5, 28.0). HES patients with a molecular aberration had increased number of thrombotic events compared to HES patients with no molecular aberrations, 37.5% versus 10.7% respectively (p = 0.053, risk ratio 3.5, 95% CI 1.01 - 12.12). Three patients with molecular aberrations died versus 1 patient with no molecular aberrations (p = 0.129, risk ratio 5.25, 95% CI 0.59 - 46.36). Among patients with at least 12 months of follow-up (n = 40, 14 with and 26 without molecular aberrations), the one-year cumulative incidence of thrombotic events was 42.9% in patients with molecular aberrations vs 11.5% without (p = 0.044, RR 3.7 95% CI 1.2-12.0). HES patients who had thrombotic events had an increased risk of death compared to those without thrombotic events (p = 0.0226, RR 11.7, 95% CI 1.8 - 75.2). Conclusions: Thrombotic complications are common in the current study of patients with HES and are associated with an increased risk of death. Although our patient cohort was small, presence of molecular aberrations had increased rates of thrombotic events and mortality, suggesting an area of further study including possible therapeutic trials. Figure 1 Disclosures Brunner: Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Al-Samkari:Argenx: Consultancy; Amgen: Research Funding; Dova: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Rigel: Consultancy. Rosovsky:Bristol-Myers Squibb, Janssen: Research Funding; Bristol-Myers Squibb, Dova, Janssen, Portola: Consultancy. Fathi:PTC Therapeutics: Consultancy; Takeda: Consultancy; TrovaGene: Consultancy; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Astellas: Consultancy; Novartis: Consultancy; NewLink Genetics: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; Forty Seven: Consultancy; Jazz: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Trillium: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy; Kura: Consultancy; Boston Biomedical: Consultancy; Blue Print Oncology: Consultancy; AbbVie: Consultancy; Agios: Consultancy, Research Funding; Amphivena: Consultancy, Honoraria. Weitzman:Abbvie: Consultancy. Hobbs:Incyte: Research Funding; Bayer: Research Funding; Novartis: Honoraria; Celgene/BMS: Honoraria; Merck: Research Funding; Constellation: Honoraria, Research Funding; Jazz: Honoraria.

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Appropriateness of using vitamin K for the correction of INR elevation secondary to hepatic disease in critically ill patients: An Observational Study

10.21203/rs.3.rs-623623/v3 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Mashael Al Mutairi ◽

Omar Al Harbi ◽

Alanoud Al Duraihim ◽

Sara Aldosary ◽

...

Keyword(s):

Liver Disease ◽

Critically Ill ◽

Vitamin K ◽

Critically Ill Patients ◽

Thrombotic Event ◽

Bleeding Events ◽

Hepatic Diseases ◽

Increased Risk ◽

Severity Scores ◽

Tertiary Teaching

Abstract Background: Hepatic diseases have been associated with an increased risk of coagulopathy and increased odds of secondary thrombosis and bleeding. Using vitamin K for correction of coagulopathy in critically ill patients is controversial with limited evidence. This study aims to evaluate the efficacy and safety of vitamin K in the correction of international normalized ratio (INR) elevation secondary to liver disease in critically ill patients.Method: A retrospective study of adult ICU patients with coagulopathy secondary to liver disease admitted to a tertiary teaching hospital in Saudi Arabia. The primary outcome was to evaluate the association between vitamin K administration and the incidence of new bleeding events in critically ill patients with INR elevation secondary to liver disease. Secondary outcomes were to evaluate the incidence of a new thrombotic event, and the degree of INR correction with vitamin K. Patients were divided into two groups based on vitamin K administration to correct INR elevation. The propensity score was generated based on disease severity scores and the use of pharmacological DVT prophylaxis. Results: A total of 98 patients were included in the study. Forty-seven patients (48%) received vitamin K during the study period. The incidence of the new bleeding event was not statistically different between groups (OR 2.4, 95% CI 0.28-21.67, P=0.42). Delta of INR reduction was observed with a median of 0.63 when the first dose is given (p-value: <.0001). However, other subsequent doses of vitamin K were not statistically significant.Conclusion: Using vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower incidence of new bleeding events. Vitamin K was efficient in reducing INR level at the first dose, and other subsequent doses were not.

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Differential timing for programming of glucose homoeostasis, sensitivity to insulin and blood pressure by in utero exposure to dexamethasone in sheep

Clinical Science ◽

10.1042/cs0980553 ◽

2000 ◽

Vol 98 (5) ◽

pp. 553-560 ◽

Cited By ~ 28

Author(s):

Kathryn L. GATFORD ◽

E. Marelyn WINTOUR ◽

Miles J. DE BLASIO ◽

Julie A. OWENS ◽

Miodrag DODIC

Keyword(s):

Amino Acid ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Acid Metabolism ◽

Area Under The Curve ◽

Whole Body ◽

Acid Uptake ◽

Critical Periods ◽

Fetal Sheep ◽

Increased Risk

Numerous epidemiological studies have related an increased risk of adult-onset cardiovascular and metabolic disease to an adverse intra-uterine environment at critical periods. We have shown that fetal sheep exposed to dexamethasone for only 2 days at 27 days of gestation (term ≈ 150 days) became hypertensive adults, whereas those exposed at 64 days of gestation remained normotensive, as did controls. In the same sheep, now nearly 5 years old, we performed glucose tolerance tests and hyperinsulinaemic euglycaemic clamps to study the insulin sensitivity of glucose, amino acid and non-esterified fatty acid metabolism. Glucose tolerance, calculated as the area under the curve, after intravenous administration of bolus glucose and insulin secretion in response to a glucose challenge were not altered in any group. There were no significant differences in the insulin sensitivity of net whole-body glucose or amino acid uptake. However, suppression of lipolysis by insulin, measured as the proportional decrease in the circulating concentration of non-esterified fatty acids during the hyperinsulinaemic clamp, was 69±1.2% at steady-state plasma insulin levels (≈ 1000 m-units/l) in the group exposed to dexamethasone at 27 days of gestation, but only 50.8±6.5% in the controls (P < 0.05). In the group exposed to dexamethasone at 64 days of gestation, the decrease was 66.4±5.1%, which did not reach significance compared with the controls (P = 0.10). Thus brief dexamethasone exposure during early gestation programmed hypertension independently of insulin resistance of glucose or amino acid metabolism; however, it did lead to increased insulin sensitivity of the inhibition of lipolysis, which may increase susceptibility to the development of obesity postnatally.

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Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.3.556 ◽

1990 ◽

Vol 8 (3) ◽

pp. 556-562 ◽

Cited By ~ 324

Author(s):

S Cortelazzo ◽

P Viero ◽

G Finazzi ◽

A D'Emilio ◽

F Rodeghiero ◽

...

Keyword(s):

Risk Factors ◽

Essential Thrombocythemia ◽

Thrombotic Event ◽

Historical Cohort ◽

Hemorrhagic Event ◽

Long Duration ◽

Increased Risk ◽

Hemorrhagic Complications ◽

Historical Group ◽

Thrombotic Complications

The purpose of this study was to determine which factors were associated with an increased risk of thrombo-hemorrhagic complications in a historical cohort of 100 consecutive and unselected patients with essential thrombocythemia (ET) in whom busulfan treatment was given when platelets were more than 1,000 x 10(9)/L and/or a major thrombotic or hemorrhagic event occurred. The incidence of major hemorrhagic complications was very low (0.33%/person-time at risk [pt-yr]) in comparison with that of thrombotic episodes (6.6%/pt-yr). In an adequate and appropriate control historical group of 200 patients, no severe hemorrhages were recorded and the incidence of thrombotic events was 1.2% pt-yr. Thus, the analysis of risk factors was restricted to this latter group of events. Age, a previous thrombotic event, and long duration of thrombocytosis were identified as major risk factors for thrombosis, while smoking, diabetes mellitus, hyperlipidemia, and hypertension did not influence the rate of thrombotic episodes.

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Use Of Fondaparinux For Venous Thromboembolism Prophylaxis In Critically Ill Adult Patients With Moderate Renal Insufficiency

Blood ◽

10.1182/blood.v122.21.4806.4806 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4806-4806

Author(s):

Anjan J Patel ◽

Marc Zumberg ◽

Jessica Cope ◽

Jennifer Bushwitz ◽

Abigail D Antigua

Keyword(s):

Venous Thromboembolism ◽

Renal Insufficiency ◽

Dose Reduction ◽

Critically Ill ◽

Bleeding Events ◽

Data Set ◽

Risk Of Bleeding ◽

Increased Risk ◽

Clinically Significant ◽

Dose Reductions

Introduction Fondaparinux, a selective activated Factor Xa inhibitor, is a parenteral anticoagulant primarily excreted by the kidneys. Renal insufficiency (RI), commonly encountered in the critically ill, has been shown to portend an increased risk of bleeding than in normal healthy adults. In comparison to the low molecular weight heparin dalteparin, fondaparinux has been shown to be superior for the prevention of post-surgical venous thromboembolism (VTE), however an increased rate of nonfatal bleeding has been observed. Recently, data has emerged supporting empiric dose reductions in patients with moderate RI, defined as a creatinine clearance (CrCl) between 30 and 50 mL/min. Overall, the data supporting appropriate use of fondaparinux in patients with RI is lacking. This retrospective, single center study describes our experience using prophylactic fondaparinux in critically ill patients with moderate RI. Methods We report our experience utilizing fondaparinux in a mixed medical and surgical, critically ill adult population with moderate RI. The site examined was UF Health; an 852-bed sized tertiary care hospital in Gainesville, Florida between 2006 and 2012. Moderate RI was defined as a CrCl between 30 and 50 mL/min calculated by the Cockcroft/Gault equation. Only patients treated with fondaparinux for prophylaxis of VTE were included, patients treated for other indications were excluded. Doses, dose frequency and dose adjustments were documented. If patients had anti-Xa level monitoring these values were recorded. Timing of anti-Xa levels drawn with respect to fondaparinux dosing was also noted. The primary end point of the study was the rate of clinically significant bleeding events in patients receiving at least 72 hours of fondaparinux. Clinically significant bleeding was defined as transfusion of at least two units of packed red blood cells within 48 hours of a documented bleeding event or the workup of bleeding with endoscopy or imaging. Bleeding events were screened by ICD-9 codes and validated via chart review, incidence of VTE was also noted. Results Sixty-fourpatients met inclusion criteria between October 2006 and November 2012. Two patients (3.1%) experienced clinically significant bleeding events as per our definition, both in the form of gastrointestinal bleeding. Empiric dose reductions occurred in 8 (12.5%) patients, this occurred in the form of every other day administration or dose reduction using fondaparinux 1.25mg daily. Nine (14%) patients were monitored with anti-Xa levels, none of these patients encountered bleeding events. The median anti-Xa level was 0.5 mcg/mL, which is in the target prophylactic range for in our lab. The median time interval after last dose of fondaparinux to anti-Xa level measurement was 4 hours. Seven (10.9%) patients had VTE diagnoses prior to the initiation of prophylactic fondaparinux. No patients suffered a VTE event after treatment with prophylactic fondaparinux in our data set. Conclusion We report a cohort of patients with moderate RI receiving fondaparinux for the prevention of VTE. The incidence of clinically significant bleeding was 3.1%. The risk of VTE was low, no patients suffered from a VTE after treatment with fondaparinux in our data set. The rate of bleeding is slightly higher compared to patients with normal renal function. Our experience over this 6 year period supports the notion that RI portends an increased risk of bleeding with the use of fondaparinux. Further prospective studies are needed to determine the safety and efficacy of empiric fondaparinux dose reductions in patients with RI and end stage renal disease. Anti-Xa monitoring may help reduce the risk of bleeding in this patient population by identifying those patients in whom a dose reduction may be beneficial. Disclosures: No relevant conflicts of interest to declare.

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MO721THROMBOTIC EVENTS AFTER COVID-19 INFECTION IN HEMODIALYSIS PATIENTS*

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab097.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Amir Shabaka ◽

Enrique Gruss ◽

Eugenia Landaluce-Triska ◽

Eduardo Gallego-Valcarce ◽

Clara Maria Cases Corona ◽

...

Keyword(s):

Pulmonary Embolism ◽

Thrombotic Event ◽

Kidney Injury ◽

Hemodialysis Patients ◽

Infected Group ◽

Maintenance Hemodialysis ◽

Stroke Incidence ◽

Increased Risk ◽

Thrombotic Complications

Abstract Background and Aims There is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19. Method We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes. Results 185 prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was 38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the follow-up period. The median time from diagnosis of SARS-CoV-2 to the first thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-CoV-2 compared to non-infected patients (see Figure 1). Mean survival from thrombotic event was 6.1±0.4 months in the COVID-infected group, compared to 6.97±0.04 months in the non-infected group (p<0.001). Multivariate regression analysis showed that COVID-19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment and previous thrombotic events (OR 26.4, 95% CI 2.5-280.6, p=0.01). Clinical and laboratory markers did not predict thrombotic events. Conclusion There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

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