Antithrombotic therapy in the management of hospitalised patients with COVID-19.

Hospitalised patients with coronavirus disease 2019 (COVID-19) are at a significantly higher risk of having thromboembolic events while in hospital and in the immediate post-hospital discharge period. Based on early data from observational studies, multiple high quality randomised controlled trials have been conducted worldwide to evaluate optimal thromboprophylaxis regimens to reduce thromboembolism and other COVID-19-related adverse outcomes in hospitalised patients. The International Society on Thrombosis and Haemostasis has published evidence-based guideline recommendations using established methodology for the management of antithrombotic therapy of COVID-19 patients, both in-hospital and in the immediate post-hospital discharge period. A good clinical practice statement supplemented these guidelines based on topics for which there was no or limited high-quality evidence. This review summarises the main recommendations of these documents to serve as a quick access tool for hospital doctors to use in their everyday practice when treating COVID-19 patients.

Clinical characteristics of COVID-19 associated vasculopathic diseases.

Coronavirus disease 19 (COVID-19) has shown to be an infectious disease affecting not only of the respiratory system, but also cardiovascular system leading to different COVID-19-associated vasculopathies. Venous and arterial thromboembolic events have been frequently described among hospitalized patients with COVID-19 and inflammatory vasculopathic changes have also been observed. Several of the reported COVID-19 associated vasculopathies exhibit differences on epidemiology, clinical characteristics and outcome compared to non-COVID-19 types. This review focuses on the epidemiology, clinical, diagnostic and therapeutic characteristics as well as outcome data of COVID-19 associated thromboembolic events and inflammatory vasculopathies, elaborating similarities and differences with non-COVID-19 cohorts.

A Joint Analysis of Two Randomized Controlled Trials on Enoxaparin for Covid-19

Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s): A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms: enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among: in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s): COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s): The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).

D-dimer-driven versus standard prophylactic anticoagulation with fondaparinux in critically ill patients with COVID-19 and coagulopathy: An open-label, randomized controlled trial

Background: Anticoagulation with fondaparinux (FPX) has shown benefit to improve clinical outcomes in hospitalized patients with COVID-19. However, optimal thromboprophylaxis dosing in critically ill patients remains unknown. Purpose(s): To evaluate the effects of D-dimer-driven (DDD) FPX compared with standard prophylactic-dose (SPD) FPX in critically ill patients with COVID-19 and associated coagulopathy. Method(s): This was a single-center, open-label, two-arms, parallel-group, randomized controlled trial conducted between April 1, 2021 and Feb 28, 2022. The eligible COVID-19 patients who were critically ill (defined as a presence of critical care-level organ support at enrollment) and presented with coagulopathy were randomly assigned (1:1 ratio) to receive pragmatically defined regimens of either DDD FPX or SPD FPX throughout hospitalization. The primary efficacy outcome was a composite of all-cause mortality (ACM), acute myocardial infarction (MI), confirmed arterial (ATE) or venous thromboembolisms (VTE), assessed up to 30 days. The secondary efficacy outcomes were 30-day ACM, composite thrombotic events, progression to invasive mechanical ventilation (IMV) or ARDS, and acute kidney injury (AKI). The safety outcomes included major bleeding and clinically relevant non-major bleeding (CRNMB). Outcomes were blindly adjudicated and analysed on a 30-day intention-to-treat basis. Result(s): During allocated period, 270 (58%) of 465 patients were eligible and were equally assigned to DDD and SPD groups. The baseline characteristics were well-matched between groups (all p>0.05). At 30 days, the primary efficacy outcome was met in 49 of 135 patients (36.3%) with DDD FPX versus 47 of 135 patients (34.8%) with SPD FPX (hazard ratio [HR], 1.32;95% CI, 0.89-1.98;p=0.17). DDD group compared with SPD group revealed no significant difference in 30-day ACM (22.9% vs 31.8%;HR, 0.73;p=0.17). At 30 days, DDD group demonstrated no significant reduction in thromboembolism, i.e. acute MI (14.1% vs 11.8%;HR, 1.53;p=0.21);ATE (3.0% vs 3.0%;HR, 1.27;p=0.74);and VTE (2.2% vs 4.4%;HR, 0.69;p=0.59) when compared with SPD group. Among those not on IMV at randomization, DDD group showed no significant reduction in the proportion of patients meeting the need for IMV (18.5% vs 32.6%;HR, 0.72;p=0.18) or progression to ARDS (17.8% vs 27.4%;HR, 0.81;p=0.43). Allocation to DDD FPX had no significant effect on the proportion of patients experiencing AKI within 30 days (17.8% vs 14.8%;HR, 1.36;p=0.39). There was no significant difference between DDD and SPD groups in terms of major bleeding (2.2% vs 0%;HR, 8.35;p=0.35) or CRNMB (3.0% vs 2.2%;HR, 1.70;p=0.48) at 30 days. Conclusion(s): In critically ill patients with COVID-19 and coagulopathy, D-dimer-driven anticoagulation with fondaparinux did not significantly improve clinical outcomes at 30 days as compared to standard prophylacticdose. The risk of bleeding was not significantly increased in this trial. (Table Presented).

Arterial thromboembolism (ATE) and mortality among COVID-19 patients in the intensive care unit (ICU): prevalence and risk factors

Objective: To investigate the prevalence of arterial thromboembolic (TE) complications including stroke, peripheral arterial disease (PAD) and myocardial infarction (MI) and mortality among COVID-19 patients admitted to an ICU at a single centre hospital in the area of Klang Valley, Malaysia. The proportions of patients with ATE complication who died, and factors associated with the occurrence of ATE were explored. Method(s): Patients admitted to a single centre ICU with PCR confirmed of SARS-CoV-2 virus and received adequate thromboprophylaxis within February 2020-2021 were included in this retrospective Malaysian cohort study. ATE event is a combination of >=1 stroke, PAD and MI. Result(s): Mean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU admission, 64.2%, 53.2 % and 20.9% had underlying hypertension, diabetes and obesity respectively. Of 534 patients, 21 (3.9%) developed stroke, 39 (7.3%) MI, 1(0.2%) PAD and 22.8% died despite adequate thromboprophylaxis. In total, only 58 (10.9%) developed ATE event during their ICU admission. Significantly higher proportions of COVID-19 patients admitted to ICU who developed complications of stroke (12.3% vs. 1.5;p<0.001) and MI (16.4% vs. 4.6%;p<0.001) died. Age, duration of ICU admission, proportion of underlying hypertension, stroke, IHD, diabetes, kidney disease, troponin, D-Dimer were significantly greater among those with ATE events. Predictors of ATE event on multivariate logistic regression analysis were duration of ICU admission [OR 1.0 (95% CI 1.00-1.04)] and troponin [OR 1.3 (95% CI 1.1-1.4)] level. Conclusion(s): The overall prevalence of ATE complication among the severely ill COVID-19 patients was low (10.9%) with the overall mortality of 22.8% despite adequate thromboprophylaxis. Key predictors of ATE events included increased troponin level and duration of ICU admission. Perhaps a more aggressive preventive strategies can be undertaken to prevent further increase in the prevalence of arterial thromboembolism and death.

Oral contraceptives and stroke: Foes or friends.

Incidents of strokes are increased in young women relative to young men, suggesting that oral contraceptive (OC) use is one of the causes of stroke among young women. Long-term exposures to the varying combinations of estrogen and progestogen found in OCs affect blood clotting, lipid and lipoprotein metabolism, endothelial function, and de novo synthesis of neurosteroids, especially brain-derived 17ß-estradiol. The latter is essential for neuroprotection, memory, sexual differentiation, synaptic transmission, and behavior. Deleterious effects of OCs may be exacerbated due to comorbidities like polycystic ovary syndrome, sickle cell anemia, COVID-19, exposures to endocrine disrupting chemicals, and conventional or electronic cigarette smoking. The goal of the current review is to revisit the available literature regarding the impact of OC use on stroke, to explain possible underlying mechanisms, and to identify gaps in our understanding to promote future research to reduce and cure stroke in OC users.

Virology, clinical features and diagnosis of covid 19: Review analysis

COVID-19 requires unprecedented mobilization of the health systems to prevent the rapid spread of this unique virus, which spreads via respiratory droplet and causes respiratory disease. There is an urgent need for an accurate and rapid test method to quickly identify many infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of the patients. This article aims as an outcome of review of the evidence on viral load and its virulence of SARS-CoV2,so that it will help in further understanding the fact useful for investigating and managing the COVID-19 cases. A search of available evidence was conducted in pub-med "COVID-19 viral load and virulence" and its associated characters world-wide and Google Scholar to capture the most recently published articles. The WHO and Centre for Disease Control and Prevention (CDC) database of publications on novel coronavirus were also screened for relevant publications. s of 55 articles were screened by two authors and 15 were included in this study based on the inclusion criteria. SARS-coV2, the causative agent of COVID-19 falls under the coronavirus family but it has higher infectivity compared to SARS and MERS with higher reproduction numbers(Ro). Virulence has been found to be different throughout the world,however lower compared to SARS and MERS,till date. The most common clinical features have been found to be cough and fever. RT - PCR remains the most sensitive and specific method for the diagnosis of COVID-19 although it is time consuming, costly and requires highly skilled human resources. Hence, newer modalities like RT-LAMP can be alternative for point of care diagnosis as this is both cost effective and requires less skilled human resources. Despite recent advances in disease diagnosis and treatment outcomes using latest technological advances in molecular biology, the global pandemic COVID-19 remains a major headache for governments across the world due to limited testing capacity and lack of appropriate treatment and vaccine. Copyright © 2020, Kathmandu University. All rights reserved.

Acute Limb Ischemia in COVID-19 Patients: A Single University Center Experience.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently known to lead to high rates of thrombotic complications. Of those, acute limb ischemia (ALI) was most frequently reported. Several case reports or case series had already described high mortality and amputation rates. The purpose of our study was to highlight the epidemiological, clinical, and management characteristics of coronavirus disease 2019 (COVID-19)-related ALI patients. Methods This was a monocentric, observational, and retrospective study. Records of all patients ≥18 years of age admitted with ALI and a confirmed diagnosis of COVID-19 infection between March 2020 and December 2021 were retrospectively examined. Data collected included demographics, co-morbidities, biological findings, COVID-19 pneumonia and ALI severity, anatomical location of arterial thromboembolism, treatments, and outcomes. Results During the study period, 22 patients with ALI infected with COVID-19 were evaluated. The median age was 67 years (45-88) and 18 (81.8%) were men. The main comorbidities were diabetes mellitus (36.4%), smoking (22.7%), and arterial hypertension (18.2%). All 22 patients were already diagnosed positive for SARS-CoV-2. The median duration between COVID-19 diagnosis and ALI symptom onset was six days (1-13 days). The computed tomography (CT) extent of pulmonary lesions was assessed according to the French Society of Chest Imaging. The ischemic syndrome was classified on Rutherford Stage IIA (30.4%) and IIB (43.5%). Regarding thrombotic locations, ALI had occurred essentially in the lower limbs (95% vs. 5%). A revascularization procedure was performed in 14 patients (63.6%) of the patients, and primary amputation was unavoidable in five patients (22.7%). Three patients (13.6%) did not undergo operative management, two because of their hemodynamic instability and one rejected surgery. We performed 23 revascularization procedures for 14 patients and three primary amputations. Thromboembolectomy (TE) was the technique of choice (92.8%). Below-the-knee (BTK) femoropopliteal bypass was performed in one patient. Selective tibial vessel thrombectomy was performed in four patients (28.6%). The mortality rate was 27.3%. Among survivors, two secondary amputations were needed with a limb salvage rate of 68.2%. Conclusion By the apparent end of the pandemic, our study further supports the increased risk of ALI in COVID-19-positive patients. Moreover, the results affirm the unfavorable outcomes highly impacted by rethrombosis, reinterventions, and consequently high rates of amputations and mortality.

Prophylaxis of Venous Thromboembolism in Patients Who Recovered from COVID-19

Background: Although COVID-19 has been mainly identified as a viral respiratory tract infection, studies have reported that severe COVID-19 is often complicated with coagulopathy resulting in high risk of venous thromboembolism (VTE) and mortality. In addition, COVID-19 has been regarded as a risk factor for thromboembolic events. Accumulating evidence indicates the necessity of diagnostic and prophylactic strategies against thromboembolic events in COVID-19. Currently, subcutaneous injectable drugs such as enoxaparin are widely used for prophylaxis of thromboembolic events. However, although these drugs are recommended to be used for 6 months, they are usually discontinued after 7-10 days because of administration difficulties. On the other hand, new generation anticoagulants are oral form of these drugs and can be safely used for a longer time. Since there is still not an indication of these drugs for the prophylaxis of thromboembolic events following COVID-19, they are not routinely used in clinical practice. Method(s): COVID-19 patients discharged from inpatient clinic between 01.06.2021 and 01.12.2021 were referred to our outpatient clinic due to regulation of anticoagulant medication. We administered new generation oral anticoagulants for prophylaxis against thromboembolic events in 50 patients. For this purpose, we used 30 mg 1x1 edoxaban, 15 mg 1x1 rivaroxaban or 2.5 mg 2x1 apixaban for 6 months. On the other hand, it was noticed from hospital medical records that 100 patients followed-up in inpatient clinic during that period received enoxaparin injections for 10 days during hospitalization and no further anticoagulant medication was given. short term or long term Results: In general, we obtained successful outcomes in patients who were administered oral anticoagulants.On the contrary, some of the patients who did not use these drugs developed thromboembolic events following COVID-19 disease. None of the patients receiving oral anticoagulants developed thromboembolic events during 6-month followup. On the other hand, among the patients who received enoxaparin injections, three patients developed venous thromboembolism(deep vein thrombosis in two patients and pulmonary embolism in one patient, all of them nearly one month later), and two patients arterial thromboembolism Method of prophylaxis Conclusion(s): We compared long-term oral anticoagulant medications and short term injections and found that thromboembolic events were not encountered in longterm oral medication. We suggest routine use of new anticoagulants as prophylactic agents against thromboembolic events following COVID-19 disease..

Low incidence of thromboembolism in hospitalized COVID-19 patients despite a very low thromboprophylaxis rate in Thailand

Background: International guidelines recommend thromboprophylaxis for hospitalized coronavirus disease 2019 (COVID-19) patients due to high prevalence of thromboembolism (TE). However, thromboprophylaxis is uncommonly prescribed in Thailand. Aim(s): To determine the incidence of TE and the mortality rate of hospitalized COVID-19 patients in Thailand. Method(s): We retrospectively reviewed medical records of COVID-19 patients admitted to King Chulalongkorn Memorial Hospital between February 2020 and August 2021. Result(s): There were 7452 hospitalized COVID-19 patients with 460 (6.2%) intensive care unit (ICU) patients. The decision of thromboprophylaxis was based on the discretion of attending physicians. Only 85 (1.14%) patients received anticoagulants due to new TE without thromboprophylaxis (43;0.58%), thromboprophylaxis (36;0.48%) or preexisting conditions (6;0.08%). Of 43 newly identified TE, there were 33 (0.44%) venous TE and 10 (0.14%) arterial TE. Among 43 TE, 29 were treated in ICU with an estimated incidence of 6.3% (29 of 460). The incidence of TE in non-ICU patients was very low (0.2 %;14 of 6992). Of 36 receiving standard-dose enoxaparin thromboprophylaxis, 3 (8.3%) developed venous TE. The overall mortality rate was 1.7% (126 of 7452), while the mortality rate in patients with TE was as high as 41.3% (19 of 46). Compared to patients without TE, patients with TE had a substantially increased risk of death (odds ratio of 48.0, 95% confidence interval, 25.9, 89.0;p < 0.0001). Conclusion(s): The incidence of TE in hospitalized COVID-19 patients was lower than those reported from Western countries despite a very low thromboprophylaxis rate in Thailand. Routine thromboprophylaxis for hospitalized COVID-19 Thais may not be cost-effective. However, ICU patients were at higher risk of TE. Patients who developed TE were at greater risk for death.

Convalescent plasma therapy does not increase the risk of thromboembolism in the treatment of COVID-19: A systematic review and meta-analysis

Background: Convalescent plasma therapy (CPT) has been issued emergency use authorization for the treatment of SARS-CoV-2 (COVID-19) by the United States Food and Drug Administration. The presence of coagulation factors in CPT in combination with the pro-thrombotic state COVID-19 patients are in may potentiate their risk of thrombotic events. Aim(s): To assess the risk of venous thromboembolisms (VTE) and arterial thromboembolisms (ATE) in COVID-19 patients undergoing CPT. Method(s): MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials that investigated the safety and efficacy of CPT and standard of care (SOC) against placebo or SOC alone in adult COVID-19 patients. Study selection and data extraction were done in duplicate. The primary outcome was the development of VTE and ATE. The secondary outcomes were 30-day mortality, clinical improvement, length of hospitalization (LOH), sepsis/fever, and major adverse cardiovascular events (MACE). Meta-analysis was conducted using the Mantel-Haenszel random effects model. Binary endpoints and continuous endpoints were synthesized using odd ratios (OR) and mean differences respectively with 95% confidence intervals (CI). Result(s): 17 randomized controlled trials including 18566 patients were included (Table 1). The risk of VTE and ATE did not differ between the CPT and the control group. There were also no significant differences in 30-day mortality, clinical improvement, LOH, risk of sepsis/fever, and MACE. A summary of outcomes is illustrated in Table 2. Conclusion(s): Treatment of COVID-19 with CPT does not appear to be associated with an increased risk of VTE, ATE, or adverse events but also does not appear to provide mortality or clinical benefit.

Arterial thromboembolism risk assessment model in hospitalized COVID-19 patients

Background: Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications portending an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke (AIS) and myocardial infarction (MI). Aim(s): We propose to develop risk assessment model (RAM) that can risk stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). Method(s): This multicenter, retrospective study included adult patients admitted with PCR proven SARS-CoV-2 infection between 3/1/2020 and 9/5/2021. The composite outcome was in-hospital ATE events, including AIS, MI, and other ATE identified by ICD-10 codes. 49 variables, including baseline demographics, past medical history, presenting vitals and laboratory values, were categorized with multiple imputation to impute missing values. Variables selected by LASSO regression were used to build the final RAM. Result(s): Among 3531 patients from training cohort (admitted before 12/31/2020), 548 (15.5%) patients developed acute ATE, compared to 285 of 2508 (11.4%) in the validation cohort (admitted after 12/31/2020). The final score included 16 items: Male gender (1);Non-African American race (1);Age 40-59 (2), Age 60+ (4);Systolic blood pressure > = 160mmHg (1);History of cerebrovascular accident (1), Coronary artery disease (1), Smoking (1);Leukocytes > 11 K/uL (1), B-type natriuretic peptide > 100 pg/ mL (1), Lactate dehydrogenase > 192 U/L (1), Creatinine > 1.4 mg/ dL (1), Aspartate aminotransferase > 41 U/L (1), Troponin-I > 0.03 ng/mL (1), Troponin-I > 0.09 ng/mL (3), Interleukin-6 > 5 pg/mL(1), Potassium < 3.5 mEq/L(1), Magnesium < 1.8 mg/mL (1). RAM had a good discrimination for ATE (training AUC 0.777, 95% CI 0.756-0.797;validation AUC 0.749, 95% CI 0.721-0.778). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13) and high-risk groups (score 14+), with the incidence of ATE 2.1%, 11.3%, and 31.1%, respectively. Conclusion(s): Our prediction model based on 16 parameters commonly available at hospital admission showed moderate performance in identifying hospitalized COVID-19 patients at low and high risk for ATE.

Inflammatory and Hemostatic Markers in COVID-19 Patients with Arterial Thrombosis Are Significantly Lower at Hospital Admission than in COVID-19 Patients without Thrombosis.

Patients with Coronavirus disease 2019 (COVID-19) are at increased risk of venous thromboembolism (VTE); however, data on arterial thromboembolism (ATE) is still limited. We report a case series of thromboembolic events (TE) in 290 COVID-19 patients admitted between October and December 2020 to a Portuguese hospital. Admission levels of various laboratory parameters were evaluated and compared between COVID-19 patients with (TE) and without thrombotic events (non-TE). The overall incidence of isolated ATE was 5.52%, isolated VTE was 2.41% and multiple mixed events was 0.7%. A total of 68% events were detected upon admission to the hospital with 76% corresponding to ATE. Admissions to the Intensive Care Unit were higher in patients with TE, when comparing with the non-TE group (44% vs. 27.2%; p = 0.003). Patients with ATE presented significantly lower levels of CRP (p = 0.007), ferritin (p = 0.045), LDH (p = 0.037), fibrinogen (p = 0.010) and higher monocyte counts (p = 0.033) comparatively to the non-TE patients. These results point to an early occurrence of TE and an increased incidence of ATE over VTE. The less prominent inflammation markers in patients with TE and the early presence of TE in patients with otherwise no reason for hospitalization, may suggest a direct role of SARS-CoV-2 in the thrombotic process.

CLOTTING AND COVID-19: IT IS NOT ALWAYS VTE

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an enveloped positive stranded RNA virus that affects multiple organ systems in the body. COVID-19 venous and thromboembolic events are well documented;however, few reports of arterial thrombosis exist. Arterial embolism is reported to occur in one to five percent of patients. We present a case of a patient who experienced arterial thromboembolism. CASE PRESENTATION: A 38-year-old woman with a history of diabetes, hypertension, and recent COVID-19 pneumonia three weeks prior presented to the hospital for lower extremity weakness, paresthesias, and pain in her bilateral lower extremities. Upon examination, she was found to have bilateral cold feet, lack of sensation to toes or plantar aspect of feet, nondopplerable pedal or dorsalis pedis pulses bilaterally, dopplerable femoral pulses bilaterally. A CT angiogram of the abdomen with bilateral runoff revealed distal abdominal aortic and bilateral iliac artery thrombus, thrombus in bilateral runoff arteries. She was evaluated by vascular and started on a heparin drip. She underwent bilateral iliofemoral thromboembolectomy and bilateral iliac stents. Surgery recommended allowing demarcation in the outpatient setting, however, due to intractable pain vascular surgery determined that bilateral below the knee amputations were necessary. She underwent testing for possible hypercoagulable state and was found to have an elevated cardiolipin antibody and lupus anticoagulant (LA) screen positive which are reported in 50% of critically ill COVID-19 patients, though the clinical or pathological value of these results are unclear at this time. DISCUSSION: Several mechanisms for hypercoagulability in COVID-19 infection have been postulated. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to host angiotensin converting enzyme 2 (ACE2) proteins. ACE2 receptors can be found throughout multiple organs and specifically on endothelial cells. ACE2 maintains the endothelial integrity of vessels. Coagulation testing in COVID-19 patients reveal increased prothrombin, activated partial thromboplastin time (aPTT), platelet counts, fibrinogen levels. Increased inflammation and cytokine release lead to a hypercoagulable state. Studies have shown that cardiolipin antibodies and LA positivity are higher in patients with COVID-19 which predispose patients to venous and arterial thrombosis. CONCLUSIONS: Venous thrombosis is often considered in patients with COVID-19 and clotting complications, however, due to the growing number of case reports regarding arterial thrombosis – arterial complications must be considered in the differential. Further research regarding the mechanism of arterial thrombosis are required to better understand the pathogenesis and develop targeted therapies to prevent occurrence of arterial thrombosis. Reference #1: Cheruiyot I, Kipkorir V, Ngure B, Misiani M, Munguti J, Ogeng'o J. Arterial Thrombosis in Coronavirus Disease 2019 Patients: A Rapid Systematic Review. Ann Vasc Surg. 2021;70:273-281. doi:10.1016/j.avsg.2020.08.087 Reference #2: Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium ;Nature Reviews Cardiology Reference #3: Taha, M., & Samavati, L. (2021). Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review. RMD open, 7(2), e001580. https://doi.org/10.1136/rmdopen-2021-001580 DISCLOSURES: No relevant relationships by Gretchen Grosch No relevant relationships by Stephanie Link No relevant relationships by Soophia Naydenov No relevant relationships by Tanner Wallen

ACUTE DIGITAL GANGRENE TRIGGERED BY COVID-19 COAGULOPATHY

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: As the coronavirus pandemic continues to burden the global health care system, strong associations have emerged with hypercoagulability. Recent reports of Covid-19 support both venous and arterial thromboembolism, thus coagulopathy emerging as one of the most severe sequelae of the disease, which has also been associated with poorer outcomes. CASE PRESENTATION: A 71-year-old female with a past medical history of hypertension, type 2 diabetes, and obesity presented with progressively worsening shortness of breath and cough. She was found to be hypoxic to 80% on arrival and tested positive for COVID-19. She was subsequently intubated and admitted to the ICU. Her D-dimer was noted to be 9.04mcg/mLFEU (0-0.55mcg/mLFEU), ferritin 256ng/mL(10-291ng/mL), LDH 707 U/L(130-270U/L), CRP 138mg/L (< 10mg/L). She was treated with a ten-day course of dexamethasone and a five-day course of Remdesivir. On Day 7, purple discoloration was noted in the second to fifth digits of the left hand, concerning acute ischemia. Left upper extremity ultrasound revealed intraluminal heterogeneous echogenicity likely occlusive ulnar arterial thrombus with no flow to mid or distal segment and normal flow in the radial artery into a complete palmar arch. This was seen to be classical for micro-embolic phenomenon attributable to the hypercoagulable state associated with Covid-19 infection. Treatment with Heparin drip was initiated along with the local application of nitro paste. The patient was subsequently discharged home but re-presented a month later for gastrointestinal bleeding. At this admission, her left second digit was noted to express purulent drainage. Imaging confirmed osteomyelitis in the second through fifth digits and was referred to a tertiary center for definitive treatment. DISCUSSION: Covid-19 has been shown to provoke catastrophic inflammatory responses by triggering a dysfunctional cascade of thrombosis in the pulmonary vasculature leading to both micro and macroangiopathic manifestations. The quick progression of ischemia to digital gangrene, despite collateral circulation and early intervention, indicates severe microangiopathy. CONCLUSIONS: Thus physicians must always have a high index of suspicion for thromboembolic complications in patients with Covid-19. The development of severe complications despite prompt anticoagulation highlights the need for alternative or newer therapies like targeted immunotherapy that would effectively manage these complications of SARS-CoV-2. Reference #1: Digital Gangrene as a Sign of Catastrophic Coronavirus Disease 2019-related Microangiopathy Jessica S. Wang, MD,* Helena B. Pasieka, MD, MS,† Vesna Petronic-Rosic, MD, MSc, MBA,† Banafsheh Sharif-Askary, MD,* and Karen Kim Evans, MDcorresponding author Reference #2: Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, Navarro Fernández I, Ruiz-Villaverde R, Falkenhain-López D, Llamas Velasco M, García-Gavín J, Baniandrés O, González-Cruz C, Morillas-Lahuerta V, Cubiró X, Figueras Nart I, Selda-Enriquez G, Romaní J, Fustà-Novell X, Melian-Olivera A, Roncero Riesco M, Burgos-Blasco P, Sola Ortigosa J, Feito Rodriguez M, García-Doval. Classifications of the cutaneous manifestations of Covid-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Jul;183(1):71-77. doi: 10.1111/bjd.19163. Epub 2020 Jun 10. Reference #3: Mouhamed Yazan Abou-Ismail 1, Akiva Diamond 2, Sargam Kapoor 3, Yasmin Arafah 2, Lalitha Nayak 4.The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management Thromb Res. 2020 Oct;194:101-115. doi: 10.1016/j.thromres.2020.06.029. Epub 2020 Jun 20. DISCLOSURES: No relevant relationships by Navyamani Kagita No relevant relationships by ABHIGNA KULKARNI No relevant relationships by Rajesh Thirumaran

Critical leg ischemia related to COVID 19 in doubly vaccinated patients

Background: COVID and venous thromboembolism in unvaccinated population is now a well-established entity but this case is unique as the 1) patient had both COVID vaccines and then tested positive for COVID and 2) presented with vague symptoms and had minimum oxygen requirement 3) developed arterial thromboembolism and acute leg ischemia after 4 days of admission leading to limb amputation ultimately. Data on COVID and COVID vaccine's association with Arterial thromboembolismstill needs to be explored. In our case it was challenging to establish whether the thromboembolism was a complication of vaccine, COVID or was that the result of synergistic interaction of both. Case Presentation: 61 Years old gentleman presented to Emergency Department with vague history of lethargy ongoing for 3-4 weeks and no significant prior co-morbid except sickle cell trait. He had received both doses of COVID vaccine 2 months before presentation and denied any shortness of breath, cough, fever or pain. On presentation he was de-saturating to 77% on Room air and had bilateral crepitations in his chest with PO2 of 7.4 kPa on ABG and raised inflammatory markers on bloods. His CXR showed changes consistent with COVID and he was started on Dexamethasone. His COVID test came back as positive. Throughout his staymaximumamount of oxygen required by him was 36% day1 which improved to 28-32% later, he had not been tachypneic or tachycardiac. His d-dimer was raised at 3000 which was thought to be COVID related, and the decision was taken to perform CTPA to rule out Pulmonary embolism if oxygen requirement worsens. His oxygen requirement continued to remain static with a little improvement or worsening. His inflammatory markers also got better. On Day 4 Patient complained of Right Leg pain. On further enquiry he revealed pain has been ongoing for last 2-3 weeks. His legs were bilaterally ice cold to touch and had hair loss in bilateral legs, pulses in both legs down the femoral artery were not palpable bilaterally. His blood gas Lactate was 2.6 with worsening inflammatory markers but no fever spikes or worsening in oxygen requirement or any other symptoms apart from leg pain. He was immediately seen by vascular Surgery team and was started on therapeutic anticoagulation suspecting acute leg ischemia. CT Angio report showed: Occlusion of Right iliac system, common femoral artery part of the SFA and all the popliteal artery and tibial vessels and unstable thrombus in the left common iliac artery causing severe stenosis and occluded left TP trunk. He was continued on therapeutic anticoagulation and then underwent Right iliofemoral embolectomy, on table angiogram, left common iliac angioplasty via left groin approach and right above knee amputation. Postoperatively he remained well and was tested COVID negative later. He was then discharged to Rehab from hospital for further care. Discussion and conclusion: We suggest that COVID patients with significantly raised d-dimers should be investigated for hidden thromboembolic focus in same way in non COVID patients and not just in lungs but in other organ systems as well. There should be some guidelines regarding increased dose prophylaxis or a flowchart to investigate for these thromboembolic association in COVID.

Tolerability of abiraterone (abi) combined with olaparib (ola) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Further results from the phase III PROpel trial

Background: The Phase III PROpel (NCT03732820) trial demonstrated at interim analysis a statistically significant clinical benefit from combining ola + abi in the first-line (1L) mCRPC setting vs placebo (pbo) + abi. Benefit was seen irrespective of a pt's homologous recombination repair mutation (HRRm) status;median radiographic progression-free survival (rPFS) 24.8 for ola + abi vs 16.6 months for pbo + abi (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54-0.81;P<0.0001). The safety profile of ola + abi was shown to be consistent with that for the individual drugs. We report additional interim safety analysis from PROpel. Methods: Eligible pts were ≥18 years with mCRPC, had received no prior chemotherapy or next-generation hormonal agent treatment at mCRPC stage, and were unselected by HRRm status. Pts were randomized 1:1 to abi (1000 mg qd) plus prednisone/prednisolone with either ola (300 mg bid) or pbo. Primary endpoint was investigator-assessed rPFS. Safety was assessed in all pts receiving ≥1 dose of study treatment by adverse event (AE) reporting (CTCAE v4.03). Results: 398 pts received ola + abi and 396 pbo + abi (safety analysis set). At data cut-off (July 30, 2021), median total duration of exposure for ola was 17.5 vs 15.7 months for pbo, and for abi 18.2 months in the ola + abi arm and 15.7 in the pbo + abi arm. Anemia (n=183) was the most common AE in the ola + abi arm, and 34% of these 183 events were managed by dose interruption, 23% by dose reduction, and 8% resulted in treatment discontinuation. Anemia and pulmonary embolism (PE) were the only Grade ≥3 AEs in ≥5% of pts (anemia: ola + abi, 15.1% vs pbo + abi, 3.3%;PE: 6.5% vs 1.8%, respectively). Most PEs were detected incidentally on radiographic imaging (69.2% and 71.4% in the ola + abi and pbo + abi arms, respectively) and no pts discontinued. More pts in the ola + abi arm experienced venous thromboembolism (Table). Arterial thromboembolism and cardiac failure AEs were balanced between the treatment arms. No AE of myelodysplastic syndrome/acute myeloid leukemia was reported in either treatment arm. COVID-19 was reported more frequently with ola + abi (8.3% vs 4.5%). Conclusions: PROpel demonstrated a predictable safety profile for ola + abi given in combination to pts with 1L mCRPC unselected by HRRm status. AEs of cardiac failure and arterial thromboembolism were reported at similar frequency in both treatment arms. The majority of PEs were asymptomatic. The safety profile of abiraterone was not adversely impacted by its combination with olaparib.

Outcomes of acute limb ischemia in COVID-19.

OBJECTIVE: The inflammatory cascade caused by severe acute respiratory syndrome coronavirus 2 infection may result in arterial thrombosis and acute limb ischemia (ALI) with devastating consequences. The aims of this study were to compare outcomes of ALI in the lower extremities in patients with and without coronavirus disease 2019 (COVID-19), and to determine if ALI development in the context of COVID-19 portends a worse prognosis compared with COVID-19 without ALI. METHODS: Queries were built on TriNetX, a federated network of health care organizations across the United States that provides de-identified patient data. International Classification of Diseases, 10th revision diagnostic codes were used to identify patients with acute limb ischemia of the lower extremities and COVID-19. The study timeframe was defined as January 20, 2020 to May 20, 2021. Statistical analyses, including propensity-score matching, were done through TriNetX's internal software. Outcomes looked at are rates of mortality, stroke, myocardial infarction, major adverse limb events, re-intervention, respiratory failure, sepsis, mental health complications, and acute renal failure. Baseline cohort characteristics were also collected. RESULTS: Patients with ALI with COVID-19 (ALI C19+; n = 526) were significantly less likely than patients with ALI without COVID-19 (ALI; n = 14,131) to have baseline comorbidities, including nicotine dependence (18% vs 33%; P < .0001). In contrast, ALI C19+ patients had significantly more comorbidities than hospitalized patients with COVID-19 without ALI (n = 275,903), including nicotine dependence (18% vs 10%; P < .0001). After propensity matching was performed, ALI C19+ patients had significantly higher rates of mortality (24.9% vs 9.2%; P < .0001), major adverse limb events (5.8% vs 2.9%; P = .0223), and acute renal failure (22.2% vs 14.9%; P = .0025) than patients with ALI. Compared with hospitalized patients with COVID-19 without ALI, ALI C19+ patients had higher propensity-matched rates of respiratory failure and being placed on assisted ventilation (32.9% vs 27%; P = .0369), sepsis (16.9% vs 12.2%; P = .0288), acute renal failure (22.1% vs 14.6%; P = .0019), and mortality (24.7% vs 14.4%; P < .0001). CONCLUSIONS: Patients who developed ALI following COVID-19 present with significantly different demographics and comorbidities from those who develop ALI without COVID-19. After controlling for these variables, higher rates of major adverse limb events, acute renal failure, and mortality in patients with ALI with COVID-19 suggest that not only may COVID-19 precipitate ALI, but it may also exacerbate ALI sequelae. Furthermore, development of ALI in COVID-19 portends worse prognosis compared with patients with COVID-19 without ALI.

COVID Coagulopathy and Thrombosis: A Systematic Review

Introduction: Since the onset of the SARS-CoV-2 pandemic, haematological laboratory abnormalities and thrombotic complications have been observed among infected patients. We aimed to highlight key pathophysiological mechanisms of COVID-19-associated coagulopathy and to summarize incidence rates of venous and arterial thrombotic events, comorbidities conferring risk, and current treatment guidelines including data from ongoing clinical trials. Methods: A systematic review was performed according to PRISMA recommendations of case–control studies, cohort studies, observational studies and randomized clinical trials (RCTs) published between 1 December 2019 and 30 September 2021 within PubMed and Web of Science. Inclusion criteria were English language, adult patients and at least one coagulation parameter described. Results: 2,554 records were screened, from which 59 studies were included. Abnormalities in several laboratory parameters were associated with worse clinical outcomes including elevations in prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen, von Willebrand factor antigen/activity and lupus anticoagulant antibodies. Rates of venous and arterial thromboembolism varied significantly among studies performed early in the pandemic and across different nations. Pathophysiological mechanisms included vascular endotheliopathy, increased inflammation and macrophage activation, neutrophil extracellular traps, antiphospholipid antibody production and obesity/adipose tissue signalling. Current recommendations for management of COVID coagulopathy from various societies include the use and dosing of systemic anticoagulation to prevent thrombotic sequelae in the outpatient, inpatient and critical care settings. The optimal anticoagulant dose for thromboprophylaxis in the inpatient and critical care settings is currently not well established. Conclusions: SARS-CoV-2 infection can cause a distinct form of coagulopathy, with thromboembolic complications leading to significant morbidity and mortality. The optimal treatment requires further refinement pending the results from key ongoing RCTs.

Severe arterial thromboembolism associated with COVID-19 infection

Purpose: The purpose of our report is to present two patients with acute peripheral arterial thrombosis as a result of COVID-19 infection and discuss the unique features of arterial thrombosis in patients suffering from COVID-19. Case Report: We present a 66-year-old female and a 53-year-old male with proven COVID-19 infection who developed acute lower limb ischemia. Common features in both patients were a multi-segment arterial occlusion in previously healthy arteries, developing despite prophylactic anticoagulation about 15 days after the onset of COVID-19 symptoms. Limb salvage was achieved by early diagnosis and expedited thrombectomy. Conclusion: COVID-19 associated arterial thromboembolism has several unique features reflecting the underlying pathogenetic mechanism which involves a combination of coagulopathy and endothelial dysfunction. Clinical vigilance allowing early diagnosis and expedited surgery remains the key to a successful outcome.