OCCUCON 2021 Abstracts

The proceedings contain 31 papers. The topics discussed include: occupational health risk assessment (OHRA) tool for estimating occupational health risk;OH IH emerging risk preparedness - shutdown activities;annoyance among staff and noise in a tertiary care hospital in New Delhi, India: a pilot study;epidemiological study on occupational health psychology in doctors, nurses and physiotherapists in Anand, Gujarat;psychological impact and educational challenges of Covid-19 pandemic among teachers in Goa;practices during Covid-19 pandemic - a case study of refinery in oil and gas exploration industry;respiratory and auditory impairment among sponge iron plant workers, Goa, India: a comparison study;suspected trauma at work place causing axillary vein thrombosis: a case report;health status of workers and their families in selected brick kilns in Anekal Taluk, Bangalore Urban District, Karnataka;and occupational health problems and perceived health hazards among dairy farmers residing in Mugalur gram panchayat, Karnataka: a mixed method study.

THE CLOT THICKENS: THE CASE OF A YOUNG MALE WITH RECURRENT PULMONARY EMBOLISMS

SESSION TITLE: Rare Cases with Masquerading Pulmonary Symptoms SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Paget-Schroetter (PS) syndrome, also known as venous thoracic outlet syndrome, is a primary thromboembolic sequela of compression of the subclavian vein. CASE PRESENTATION: A previously healthy 24 year old male presented with shortness of breath and cough. He had recently been exposed to COVID. He denied fever, diarrhea, vomiting, leg swelling, and rashes. On physical exam he was tachycardic, had no murmurs or JVD, and was CTAB with no wheezing or rales. Labs were significant for a WBC of 17k, and troponin of 0.033. CTA of the chest showed multiple filling defects in the pulmonary arteries consistent with Pulmonary Embolism (PE). He was started on a heparin drip. All COVID testing was negative. Lower extremity venous doppler ultrasounds (US) were negative for DVT. His respiratory status improved, and he was discharged on apixaban with the diagnosis of PE provoked by possible COVID infection. He returned approximately 2 months later with exertional dyspnea and upper extremity swelling and was found to have recurrent PE despite having been compliant with his apixaban. Upper extremity venous doppler US was significant for DVT in his right subclavian vein. He was placed on warfarin. At this time his hypercoagulable workup was also negative. Symptoms persisted despite being on warfarin with outpatient monitored INR. A venogram was ordered to evaluate upper torso blood flow. The venogram was remarkable for high-grade stenosis of the right subclavian vein. This finding led to the consideration of thoracic outlet syndrome aka Paget-Schroetter (PS). DISCUSSION: PS is a rare clinical entity that results from stress placed on the endothelium of the subclavian vein as it passes between the junction of the first rib and the clavicle. It can predispose otherwise healthy patients to recurrent venous thromboembolisms that are refractory to anticoagulation. The clinical features usually include upper extremity swelling and pain which is exacerbated by repetitive or strenuous exercise. Venous collaterals can also be seen in some patients. Evaluation should include some form of upper extremity Doppler and a CT/MR venogram or venography to make the final diagnosis. Treatment may involve anticoagulation, thrombolysis, and/or surgical decompression. Best results are seen with early thrombolysis and surgical decompression. If caught early and treated appropriately, PS has a good outcome with few long-term sequela. CONCLUSIONS: Our goal was to describe a patient with an uncommon cause for recurrent venous thromboembolisms that were refractory to anticoagulation. Our patient's presentation of PS serves to describe many aspects of the disease process, evaluation, diagnosis, and management as seen in the case presentation. The patient's demographic fit the epidemiological profile age of 20s-30s with typical imaging findings and pertinent negative workup which would lead providers to this rarer diagnosis. Reference #1: Saleem T, Baril DT. Paget Schroetter Syndrome. [Updated 2022 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK482416/ Reference #2: Alla VM, Natarajan N, Kaushik M, Warrier R, Nair CK. Paget-schroetter syndrome: review of pathogenesis and treatment of effort thrombosis. West J Emerg Med. 2010;11(4):358-362. Reference #3: Karl A. Illig, Adam J. Doyle, A comprehensive review of Paget-Schroetter syndrome, Journal of Vascular Surgery, Volume 51, Issue 6, 2010,Pages 1538-1547,ISSN 0741-5214, https://doi.org/10.1016/j.jvs.2009.12.022. DISCLOSURES: No relevant relationships by Jonathan Marks No relevant relationships by Zachary Stachura

Thrombosis in unvaccinated and Gam-COVID-Vac-vaccinated patients with COVID-19

Aim. To analyze the incidence of thrombotic events in unvaccinated and Gam-COVID-Vac-vaccinated patients with coronavirus disease 2019 (COVID-19). Material and methods. This prospective study included 316 patients (group 1) vaccinated with two doses of Sputnik V (Gam-COVID-Vac) hospitalized between November 20, 2020 and June 1, 2021 for COVID-19. Group 2 included 754 unvaccinated patients with a positive polymerase chain reaction test for SARS-CoV-2. Results. During inhospital period, deaths were recorded only in unvaccinated patients (group 1 — 0%;group 2 — 10,7% (n=87);p<0,0001). Among unvac-cinated patients, the following thrombotic events were more common: upper-extremity deep vein thrombosis (group 1 — 0,63% (n=2);group 2 — 5,4% (n=41);p=0,0003), lower-extremity deep vein thrombosis (group 1 — 2,21% (n=7);group 2 — 11,4% (n=86);p<0,0001), pulmonary embolism (PE) (group 1 — 0%;group 2 — 3,4% (n=26);p=0,0008), lower limb arterial thrombosis followed by thrombectomy (group 1 — 0,31% (n=1);group 2 — 12% (n=91);p <0,0001), lower limb arterial retrombosis after retrombectomy (group 1 — 0,31% (n=1);group 2 — 8,7% (n=66);p<0,0001), lower limb amputation (group 1 — 0%;group 2 — 8,7% (n=66);p<0,0001), composite endpoint (group 1 — 3,8% (n=12);group 2 — 55,2% (n=416);p<0,0001). In the long-term follow-up period (125,5±26,5 days), recurrent COVID-19 developed significantly more often in unvaccinated patients (group 1 — 0,63% (n=2);group 2 — 3,6% (n=24);p=0,007). All arterial and venous thromboses, limb amputations were diagnosed only among unvaccinated patients. Conclusion. Vaccination with Sputnik V (Gam-COVID-Vak) prevents the severe COVID-19 with the development of deaths, pulmonary embolism, venous and arterial thrombosis.

UPPER EXTREMITY DEEP VENOUS THROMBOSIS AFTER BNT162B2 MRNA COVID-19 VACCINE

CASE: A 60-year-old woman with past medical history including hypertension, nephrolithiasis, and Covid-19 4 months prior presented to the emergency department with 3 days of substernal chest pain radiating toward the back and shoulders 6 days after receiving her second dose of the BNT162b2 mRNA Covid-19 vaccine (Pfizer/BioNTech) in her left deltoid. The patient tested negative for Covid-19 and denied shortness of breath, cough, fever, or dyspnea on exertion. Her ECG was notable for more pronounced t-wave inversions in III and aVF, but further cardiac workup was unremarkable, and she was discharged the next day. The patient re-presented to care 6 days later with left arm pain, erythema, edema, and warmth. Her left bicep circumference was 31cm versus 28cm on the right. Upper extremity duplex ultrasound (US) was remarkable for deep venous thrombosis (DVT) of the left internal jugular, subclavian, axillary, and basilic veins. MRI angiogram was confirmatory. Other than her occupation as a hairdresser, the patient did not have known risk factors for DVT: no personal or family history of thromboembolism, no tobacco use, took no prescription medications, and had received all ageappropriate cancer screening. Her thrombophilia workup was negative. The patient was discharged on apixaban. Eleven days later, a venogram showed persistent clot burden in the left axillary, mid-subclavian, and brachiocephalic veins. Thrombectomy, overnight tPA infusion, and left subclavian vein stenting were performed and the patient was discharged on daily apixaban and aspirin. IMPACT/DISCUSSION: As of December 10th, 2021, the vaccine adverse event reporting system yielded 464 reports of “thrombosis” after the Pfizer/ BioNTech vaccine in individuals with no reported current illness, 32 of which occurred in the upper extremity. To our knowledge, our patient represents the first report of upper extremity deep venous thrombosis (UEDVT) shortly after receipt of the Pfizer vaccine in an otherwise healthy person. UEDVT is relatively rare: it occurs in about 0.4 to 1 per 10,000 people per year and less than 20% of incidents are idiopathic. Given the scarcity of potential causes, our case may simply reflect expected background incidence. Nevertheless, the literature includes multiple case reports of DVT after mRNA Covid-19 vaccination, including cases of lower extremity DVT and DVT with pulmonary embolism (PE) after the Pfizer vaccine, and cases of lower extremity DVT, PE, and UEDVT after the mRNA-1273 (Moderna) vaccine. Given the similar mechanism of action between the Moderna and Pfizer vaccines, it is possible that the same pathophysiology underlies the reports of DVT in these vaccine recipients. CONCLUSION: Upper extremity deep venous thrombosis after Covid-19 mRNA vaccination should remain on the differential as clinicians assess chest and arm pain following vaccination. There is a possible association between the BNT162b2 mRNA Covid-19 vaccine and upper extremity deep venous thrombosis that requires further research.

Covid-19 pfizer-biontech vaccine induced vte

Case Report Between December 2019 and May 2021, there were around 200 million cases of COVID-19, with more than 3.5 million deaths all over the world. In the United States alone, there were more than thirty million cases, with around six hundred thousand deaths attributed to COVID-19. Incidents of hypercoagulability after receiving different types of COVID-19 vaccine have been reported. The incidence of deep vein thrombosis (DVT) is about 1 in 1000, and about 50% of these patients with DVT develop pulmonary embolism (PE). The incidence of DVT affecting the upper extremity exceedingly rare with an approximate incidence of 1 in 10,000. While patients receiving anticoagulation are still at risk of DVT, data on apixaban reflects a 98% protection from recurrent thrombosis. Hypercoagulability including DVT and PE is always a rising concern in patients with COVID-19 pneumonia. We are reporting a case of a hypercoagulability state in 73-year-old lady after receiving first and second dose of Pfizer vaccine;despite being on apixaban. she has a past medical history of COPD on 2 L home oxygen. She presented with acute hypoxic respiratory failure few days after receiving the first dose of COVID-19 Pfizer vaccine. Imaging revealed right interlobar pulmonary embolism and right superficial femoral vein thrombosis without any provoking factors. She improved clinically and was discharged on apixaban. Few months later she came in with right upper extremity DVT, 7 days after receiving a second dose of Pfizer vaccine. Transesophageal Echo revealed a round mass in the left atrial appendage, which was likely a thrombus, she was discharged on warfarin. Incidence venous thromboembolism is about 1 in 1000 individuals in the United States. Several factors can increase the hypercoagulable state. SARS-COV-2 is hypothesized to increase the risk of thromboembolism by infecting cell expressing surface receptors of ACE-2 by binding the SARCOV-2 spike protein and activating cell pyroproptosis which activates neighboring cells inflammatory response and then activate coagulation pathway. BioNTECH mRNA vaccine induces immune response by engulfing S protein mRNA into the cell to produce spike protein and induce antibody production against SARS-COV-2 spike protein. At this time, this is the Third reported Vaccine related VTE after reporting a Pfizer BioNTech vaccine induced DVT on January 2021 After ruling out other causes of VTE in this case as well as the time between receiving the vaccine and the onset of symptoms, vaccine-induced thrombosis is the most likely cause for our patient's thrombosis, including venous thrombosis, pulmonary embolism, and left atrial appendage thrombosis. The mechanism remains unknown but may possibly be due to enhanced immune response to the vaccine. In patients at increased risk of thrombosis, BioNTech mRNA vaccination may induce Intravascular Coagulation, venous thromboembolism, possibly due to enhanced immune response to spike protein production.

Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI)

Introduction Hemophilia A and B are rare bleeding disorders characterized by ineffective clot formation due to impaired thrombin generation as a result of deficiency of FVIII or FIX, respectively. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic targeting antithrombin to restore thrombin generation and rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Here, we present the safety and efficacy of fitusiran prophylaxis for PwHI in a phase 3 study (ATLAS-INH;NCT03417102). Methods The ATLAS-INH study is a randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of fitusiran in PwHI. Eligible males ≥12 years receiving on-demand treatment with bypassing agents (BPA) were randomized in a 2:1 ratio to receive once monthly 80 mg SC fitusiran prophylaxis or continue with on-demand BPA. The primary endpoint is annualized bleeding rate (ABR) in PwHI on fitusiran prophylaxis compared to those on BPA on-demand in the efficacy period. The secondary endpoints include spontaneous ABR, joint ABR, and quality of life (QoL) measured by Haem-A-QoL. Results 57 subjects were randomized into the study. Mean (range) age of the study participants at screening was 28.4 (13-63) yrs. Statistical significance was achieved for primary and all secondary endpoints with significant reduction in ABRs of treated bleeds: all, spontaneous and joint bleeds for fitusiran vs on-demand BPA arm (Table 1). A total of 25 patients in fitusiran arm (65.8%) had zero treated bleeding events. Efficacy of fitusiran prophylaxis treatment was seen in both hemophilia A and hemophilia B patients with inhibitors. Statistical significance was also achieved for improvement in physical health domain score, with a difference (95% CI) of -28.72 (-39.07 to -18.37, p-value <0.0001) as well as overall HRQoL and between fitusiran and on-demand BPA arms. Overall, 38 patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm experienced at least 1 treatment emergent adverse event (TEAE). A total of 13 treatment emergent serious adverse events (TESAEs) were reported in 7 patients (17.1%) in the fitusiran arm and 8 TESAEs were reported in 5 patients (26.3%) in the on-demand BPA arm. All TESAEs were reported in 1 patient each;in the fitusiran prophylaxis arm these included events of device related infection, hematuria, spinal vascular disorder, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis and asymptomatic COVID-19. One patient (2.4%) in the fitusiran arm experienced TEAEs that resulted in study drug discontinuation (spinal vascular disorder and thrombosis). There were no fatal TEAEs reported. Conclusions This Phase 3 study demonstrated the efficacy of the 80 mg monthly subcutaneous prophylaxis dose of fitusiran in people with hemophilia A or B with inhibitors. Specifically, fitusiran significantly reduced bleeding with a median ABR of zero and significant proportion of people with zero bleeds, resulting in a meaningful improvement in health-related quality of life. Reported TESAEs were generally consistent with what is anticipated in an adult and adolescent population with severe hemophilia A or B with inhibitors, or with the previously identified risks of fitusiran. A revised fitusiran dosing regimen with reduced dose and dose frequency is currently being evaluated in ongoing clinical studies. [Formula presented] Disclosures: Young: Genentech/Roche, Grifols, and Takeda: Research Funding;Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy. Kavakli: Roche: Consultancy, Other: Clinical Trial Support;Novo Nordisk A/S: Consultancy, Other: Clinical Trial Support;Takeda: Consultancy, Other: Clinical Trial Support. Poloskey: Sanofi: Current Employment, Current equity holder in publicly-traded company. Qui: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kichou: Sanofi: Current Employment, Current equity holder in publicly-tr ded company. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company;WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Mei: Sanofi: Current Employment, Current equity holder in publicly-traded company. Rangarajan: Sanofi: Other: Advisory Board;Pfizer: Other: Advisory Board;Reliance Life Sciences: Consultancy;Takeda: Other: Advisory Board, Conference Support, Speakers Bureau.

Determining the Rate of Anti-PF4 Antibody Positive Results in Patients Presenting with Venous Thrombosis but a Normal Platelet Count Following ChAdOx1 Ncov-19 Astrazeneca Vaccination: An Australian Combined State Testing Centre Experience

Introduction The CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed “Thrombosis with Thrombocytopenia Syndrome” (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to platelet factor 4 (PF4)[4, 5]. TTS commonly presents with cerebral venous sinus thrombosis (CVST) or splanchnic vessel thrombosis (SVT), but outside of TTS, CVST and SVT are uncommon, with an overall incidence of less than 0.5 per 100,000 [5-7]. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are also associated with TTS, however the background incidence of venous thromboembolism (VTE) is much higher, with 1-2 events per 1000 patients per year[7, 8]. Therefore, many patients will present with new VTE and a recent exposure to the AZ vaccine, requiring consideration of investigation for TTS. Recent data suggests that PF4 antibodies can be seen in up to 8% of patients without thrombosis but following AZ vaccination[9]. We hypothesised in patients with recent AZ vaccination, new VTE but with a normal platelet count, that the incidence of a PF4 antibody is similar to this background rate of PF4 positivity. If confirmed, then presence of a normal platelet count despite new VTE and recent vaccination may exclude TTS without the need for PF4 antibody testing. We present our preliminary data on the rates of PF4 antibody positivity amongst patients with VTE, recent AZ vaccination and a normal platelet count at presentation. Aim and Methods To assess the incidence of PF4 ELISA positive results in patients with confirmed VTE, recent vaccination (within 4-42 days) with the first dose of AZ vaccine, and platelet count greater than 150x10 9/L. A retrospective audit of cases referred with suspected TTS to Monash Pathology, Melbourne, Victoria, and New South Wales Health Pathology at Royal Prince Alfred Hospital and St George Hospital sites Sydney, New South Wales, Australia, for testing for anti PF4 antibodies from 1 st April to 31 st July 2021. Patient sera were tested for the Anti-PF4 antibody using the STAGO Asserachrom HPIA IgG ELISA (Asnières sur Seine, France). For patients with a positive PF4 antibody test additional testing was sought for either the presence of platelet activating antibodies with a flow cytometry-based assay or the presence of spontaneous serotonin release without heparin in the serotonin release assay. Results From April 1 st to July 31 st 350 tests were run on 332 patients. 91 patients met our criteria, of whom 51 were female and 40 male, with a median age of 73 years. Median platelet count at presentation was 226x10 9/L, and median D dimer values were 10 times the upper limit of normal. 86 patients had either DVT, PE or both, including 2 with upper limb DVT, and 5 patients had PE with concurrent arterial events (1 axillary artery thrombosis, 3 arterial strokes, 1 coronary artery thrombosis). Further details are presented in table 1. 82 patient samples tested negative for anti-PF4 antibodies by ELISA, 5 were positive, and were 4 weak positive/equivocal (see table 2 for further details). Of the positive results, 3 had functional testing available, of which 2 were negative, and 1 showed discordant results, with a positive SRA but negative flow cytometry. None of the weak positive/equivocal cases had functional testing results available. Of the negative ELISA results, 5 patients had functional testing results available, of which 4 were negative. One of these cases had positive testing by flow cytometry, but negative by SRA (case included in table 2). Conclusion In our Australian cohort of patients with their first dose of AZ vaccine and new VTE within 4-42days, but a normal platelet count (therefore not fulfilling the clinical criteria of TTS), the incidence of a positive PF4 antibody test was 9/91 (9.9%, 95% CI 3.7-15.9%) and only one had evidence of platelet activating antibodies. This observed rate is similar to that observed in healthy patients wi hout thrombosis who received AZ vaccination as described by Thiele et. al., 2021. Further confirmation in a larger cohort of VTE patients is required, but if confirmed, then PF4 ELISA testing in patients with VTE and normal platelet count post AZ vaccine may not be required, and should give clinicians confidence to institute routine management. [Formula presented] Disclosures: No relevant conflicts of interest to declare.