COMPARATIVE EFFICACY OF VARIOUS ANTICOAGULANTS IN COVID-19 INDIAN SUBJECTS: AN OBSERVATIONAL STUDY

Background: To assess the efficacy of various anticoagulants being prescribed in the COVID 19 induced hypercoagulability, so as to know optimally effective anticoagulant. Methods: This was a Indian observational study conducted in our covid centre at vijayawada,Andhra Pradesh between june 2020 to January 2021 . Results: A total of 100 COVID 19 subjects were included. The patients were found to be matched with respect to age, gender, diet and past history of various illnesses. Gender wise more males (60 patients)are affected when compared to females(40 patients). Age group more affected are less than or equal to 50yrs . Comorbidites like Diabetes(67patients),cardiac problems(62patients), dyslipidemia(62patients) were seen. Risk factors like smoking(52patients), alcoholism(50patients) noticed. Almost all subjects are RTPCR positive. IL- 6,CRP,LDH high in most subjects. Ferritin and PT/INR are normal in more subjects. Out of 100 patients oxygen is required in 48 subjects and BIPAP/CPAP required in 26 subjects. Death occurred in 24 patients (2 with CVA,22 with myocardial infraction). Mortality rate is more in vegetarians. More patients in our study belongs to CORADS score 4 and 5. D-dimer are increased in 67subjects. IL-6 are increased in 68patients . Frequency of subjects with raised D-dimer (p = 0.049) and CRP (p = 0.002) levels were found to be benefitted on receiving nattokinase. However, no other parameters such as IL-6 (p = 0.068) ferritin (p = 0.396), ESR (p = 0.278), PT/INR (p = 0.47) LDH (p = 0.34) or CORADS staging achieved such significant association. Also need of interventions such as Oxygen (p = 0.001), BIPAP/CPAP (p < 0.0001) were low in patients on nattokinase. No significant difference was noted in follow up investigations such as PT/INR (p = 0.31) and other markers (D-dimer, IL-6, LDH, CRP) (p = 0.55). No bleeding episodes were reported in subjects on nattokinase. Significant low rate of death was found in subjects who received nattokinase (p < 0.0001) and rivaroxaban (p < 0.0001). Also, significantly higher mortality rate was observed in subjects who required to be put on oxygen (p < 0.0001) as well as BIPAP/CPAP (p < 0.0001). Conclusions: Nattokinase simultaneously effects several key favourable benefits for thrombosis, hypertension, atherosclerosis, hyperlipidaemia, platelet aggregation, and neuroprotection in patients with COVID 19 infection. (Figure Presented).

Post-COVID-19 non-traumatic iliopsoas hematoma: A case report

Background: Critically ill COVID-19 patients have an elevated risk of experiencing hypercoagulable conditions. Currently, many COVID-19 patients have been administered anticoagulation or antiplatelet therapies to lower the risk of systematic thrombosis. Iliopsoas hematoma is a potentially fatal and rare complication of bleeding disorders or anticoagulation therapy which sometimes grows to become clinically significant. The main purpose of this case review is to emphasize the importance of diagnosing iliopsoas hematomas and the possibility of antiplatelet contribution to its development. Case Presentation: We are reporting a rare presentation of non-traumatic iliopsoas hematoma in a non-anticoagulated patient. The patient is a 59-year-old male, with known type-2 diabetes, on oral hypoglycemic medications, 3-weeks post-COVID-19. He had started aspirin 81 mg orally, once daily, to prevent thrombotic events associated with COVID 19 infection, with no anticoagulant use and no other medications. He came in through the ED, presenting with two weeks history of progressive right lower limb weakness in which an iliopsoas hematoma diagnosis was confirmed based on radiological investigation. Conclusion: The possibility of iliopsoas hematoma should be considered in non-anticoagulated patients with no inherited or acquired coagulation disorders presenting with limb weakness. The link between antiplatelet use in a COVID-19 patient and the development of soft tissue bleeding (e.g., iliopsoas hematoma) must be studied further. © 2022 [The Author/The Authors]

Treatment adherence of patients with rheumatoid arthritis during Covid-19 pandemic

Background: Covid-19 impacted not only people's lives but also slowed down the healthcare delivery system and supply chain leading to a global drug shortage.1 According to the Ministry of Statistics, India's growth in the year 2020 went down by 3.1% because of the pandemic, which impacted patient's capacity to continue with the expenditure related to chronic disease management. Rheumatoid arthritis (RA) for a patient comes with a out-of- pocket high cost long term immunosuppressive medicine and increased chances of secondary infections leads to non-adherence of patients. The current study is to observe the adherence to Janus Kinase (JAK) inhibitors in a hospital-based rheumatology service in Eastern India during the Covid-19 pandemic period. Method(s): Data of the patients enrolled physically and electronically under active follow-up in the Rheumatology Outpatient Department (OPD) of the hospital were analyzed.2 The patients with a confirmed diagnosis of RA, receiving JAK inhibitors for 6 months or more were included in the study from 21st March 2020 to 31st July 2020. A questionnaire was also administered to these patients to understand the impact of Covid-19 on the treatment of RA. Data related to demographic features, clinical, laboratory, drug history, and current treatment were collected and statistically analyzed. Result(s): Out of the total 42 patients (aged 38-76 years) who received JAK inhibitors, 24 (6 were COVID positive) were seen with the OPD during the Covid-19 pandemic. In our study, a higher proportion of patients with an annual income of INR 1M-1.5M had a 15% income decrement (Figure 1), though the patient adherence to JAK inhibitors was high compared to biologics, even in the patients who faced up to 25% reduction in annual income. Out of 24, only 4 patients stopped the treatment with JAK inhibitors due to the limited availability during the initial period of the lockdown. Overall patient adherence to JAK inhibitor treatment was 85% and was higher compared to the biologics (previous data). There was higher non-adherence in the biologic group at lower-income slabs (5-10 Lacs & 10-25 Lacs group) than in the higher income slabs, compared to JAK inhibitors inspite of better availability. Higher-income groups showed lower non-adherence in both groups. Conclusion(s): In the milieu of the Covid-19 pandemic, the treatment adherence in patients with RA was driven by the cost and availability of the medication amidst the pandemic. The association of injectable biologics with higher immunosuppression in patients perception during pandemic also affected the treatment adherence in patients. Thus it can be concluded that patient perception and availability were the main driving factor in adherence to RA therapy.

It's not the shunt: an atypical cause of fever in an infant with hydrocephalus

Case Report:We present a 5-year-old male with two days of fever, cough, vomiting, and loose stools. His history is significant for premature birth (35 weeks gestational age) and shunted hydrocephalus. A ventriculoperitoneal (VP) shunt was placed 6 days prior to presentation. Parental report included episodes of post-tussive, nonbloody, non-bilious emesis, poor oral intake, tachypnea, and increased work of breathing. Physical examination demonstrated a dehydrated infant with sunken fontanelles. He had no notable rash, no lymphadenopathy, and clear conjunctiva. His VP shunt site appeared normal without swelling or erythema. Initial evaluation showed elevated inflammatory markers -ESR 51 and CRP 12.32 mg/dL. A viral respiratory PCR panel returned positive for coronavirus (not SARS-CoV-2). A head CT scan and shunt radiography series showed no abnormalities with his shunt. The following morning, Radiology reported an incidental retropharyngeal fluid collection on a re-read of the patient's initial CT scan. A neck CT was obtained and demonstrated a fluid pocket with secondary mass effect in addition to bilateral cervical lymphadenopathy. Screening blood cultures were negative. The patient remained febrile (tmax 103.6F) and developed a transaminitis (ALT 264.9, AST 654), elevated fibrinogen 476, elevated INR 1.4, and low albumin 2.1. Abdominal ultrasound showed a normal the liver and biliary tract. His transaminitis resolved without treatment. The next day, the patient developed lip erythema and conjunctival injection. An echocardiogram showed a dilated right coronary artery (z-score of 3.59) and his inflammatory markers (ESR 26, CRP 9.63) remained elevated. Treatment was initiated with IVIG and moderate-dose aspirin. The patient defervesced, and he remained afebrile for over 48 hours prior to discharge. A repeat echocardiogram 2 days later showed a slight reduction in coronary artery dilatation (z-score 3.39). Hewas discharged on lowdose aspirin, and followed up with cardiology as an outpatient. Kawasaki's Disease (KD) is most common in children from ages 1 to 4 years and is classically characterized by persistent fever with a constellation of symptoms including limbal sparing conjunctivitis, cervical lymphadenopathy, polymorphous rash, strawberry tongue, oral changes, and extremity changes. Our patient presented at a younger age with a concurrent diagnosis of coronavirus upper respiratory tract infection. His atypical hospital course and incidental finding of retropharyngeal edema and transaminitis increased the clinical suspicion for KD. His symptoms rapidly improved after administration of IVIG. Younger patients are at an increased risk for severe complications of KD including coronary aneurysm. KD has been shown in the literature to have an association with coronavirus infection as well as presentation with retropharyngeal edema. Clinicians should consider KD in their differential even if patients do not meet all criteria for diagnosis on initial presentation. Copyright © 2023 Southern Society for Clinical Investigation.

Clinical profile and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection: a single-center observational study from South India

Background: Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious sequelae of acute COVID-19 infection affecting children. This study was done over a period of 12 months from December 2020 to November 2021 to describe the clinical presentation, laboratory abnormalities, and outcome of children with MIS-C. Method(s): Seventy-eight children below 12 years of age who satisfied the WHO diagnostic criteria for MIS-C were included in the study. Clinical parameters were recorded at admission. Relevant laboratory investigations, radiological studies, and outcome were documented. Result(s): The most commonly affected age group was 6-12 years with a female predominance. COVID RTPCR was negative in all patients. Most cases presented 2-6 weeks after the onset of acute COVID-19 infection. Lethargy, poor feeding, vomiting, abdominal pain, loose stools, cough, and cold are common symptoms of MIS-C syndrome in children and the common signs were rash, conjunctival congestion, hypotension, tachycardia, tachypnea, and hypoxemia. Gastrointestinal system was the commonly affected followed by the hepatic, renal, and cardiovascular systems. Coronary artery abnormalities were seen in 20% of cases. IVIg was the mainstay of therapy used in 95% of patients. Mortality was 1.3%. Cases responded well to IVIg and steroids. Conclusion(s): Overall, the short-term outcome was favorable with low mortality in our study cohort. One-fifth of children had coronary artery abnormalities during acute phase underscoring the need for long-term follow-up. Copyright © 2022, The Author(s).

A Series of Catastrophic Events

Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.

Cardiac tamponade as the first presentation of thymoma: A case report during COVID-19 pandemic

We report a case of neoplastic cardiac tamponade, a life-threatening condition, as the initial presentation of an anterior mediastinal malignancy. A 69-year-old gentleman with no known history of malignancy presented to the emergency department with shortness of breath, reduced effort tolerance and chronic cough. Clinically, he was not in distress but tachycardic. He was subjected to echocardiography which revealed large pericardial effusion with tamponade effect. Pericardiocentesis drained 1.5 L of haemoserous fluid. CECT thorax, abdomen and pelvis revealed an anterior mediastinal mass with intrathoracic extension complicated with mass effect onto the right atrium and mediastinal vessels. Ultrasound-guided biopsy histopathology examination revealed thymoma. Due to locally advanced disease, tumour resection was not possible, and patient was referred to oncology team for chemoradiotherapy. We report this case study not only due to the rarity of the case but also to highlight its diagnostic challenge due to the COVID-19 pandemic. Copyright © The Author(s) 2022.

Decentralised point-of-care testing for acute, chronic and infectious disease - benefits and challenges

The COVID-19 pandemic has reinforced Australia's need for diagnostic testing frameworks that are well-prepared, well-resourced, responsive, appropriately governed, scalable, interdisciplinary and collaborative.1 Point-of-care (POC) technologies offer diagnostic solutions capable of delivering individual, community and public health benefits in settings where: a) laboratory testing is not available, b) rapid turn-around time is needed, c) high loss to follow-up occurs in high-risk populations with standard of care cascades and/or d) disease transmission rates exceed laboratory response capacity. Key translational research derived from collaborative point-of-care testing networks for a) diabetes management (238 remote health services;3,233 operators;172,069 HbA1c and 51,379 urine albumin:creatinine ratio tests), b) acute care (106 remote health services;2,279 operators;32,950 blood gas, 32,689 cardiac troponin, 46,418 urea/electrolytes, 48,193 international normalised ratio tests), c) hepatitis C virus (HCV) (41 sites;110 operators;5,733 HCV tests;4,978 RNA, 755 antibody), d) syphilis screening (156 sites;1,412 operators), e) chlamydia, gonorrhea or trichomonas (51 sites;795 operators;>50,000 tests) or f) COVID-19 (101 remote health services, 733 operators, 72,624 tests) will be used to highlight operational, clinical, public health, and economic benefits of POC testing. Challenges associated with scale-up and accreditation pathways for decentralised POC testing will be discussed. Reference 1. Revised Testing Framework for COVID-19 in Australia, March 2022 Version 2.1. Communicable Disease Network Australia and Public Health Laboratory Network. Copyright © 2022

A Comparison of Pediatric Icu Presentation of Mis-C, Kawasaki Disease, Toxic Shock, and Septic Shock

INTRODUCTION: With the COVID19 pandemic there has been a rise of Multisystem Inflammatory Syndrome in Children (MIS-C) cases that have similar symptoms to Kawasaki Disease Shock Syndrome (KDSS), Toxic Shock Syndrome (TSS) and Septic Shock (SS). To differentiate between presenting clinical symptoms, laboratory values and vasoactive requirements would aide in the proper early diagnosis of these diseases. METHOD(S): This was a single center retrospective review of MIS-C, KDSS, TS, and SS patients admitted to the PICU. Mann-Whitney U testing compared each patient population to each other using admission laboratory values, VIS, fluid resuscitation, day of illness admitted, and physical exam findings. RESULT(S): SS and TS patients presented earlier to the ICU compared to MIS-C and KDSS (2 and 2 vs 4.5 and 5, p< 0.001). TS had the highest VIS compared to MIS-C (p=0.005), KDSS (p=0.009), and SS (p=0.008). MIS-C was found to utilize the least fluid resuscitation but only found to be different between MIS-C and TS (p< 0.001). MIS-C had the lowest ejection fraction compared to KDSS (p=0.02), TS (p< 0.001), and SS (p< 0.001). MIS-C patients presented with a highest CRP (24.8 mg/dL) but only found to be different from SS (p=0.01). MIS-C appeared to have a lower WBC (11.4 TH/ uL) compared to KDSS (13.3 TH/uL, p=0.004) and TSS (14.4 TH/uL, p=0.04). KDSS was found to have a greater platelet count (249 TH/uL) compared to MIS-C (128 TH/uL, p< 0.001), TSS (169 TH/uL, p=0.003), and SS (186 TH/uL, p=0.03). TSS had the largest presenting INR (1.50) compared to KDSS (1.25, p=0.009), SS (1.25 TH/uL, p =0.04) and MIS-C (1.13 TH/uL, p< 0.001). MIS-C had a lower sodium (132mmmol/L) compared to TSS (135mmol/L, p< 0.0001) and SS (138mmol/L, p< 0.0001). Patients with KDSS were found to have oral and extremity changes compared to MIS-C (p=0.02, p=0.002). KDSS likely had a cervical lymph node on presentation compared to TSS and SS (p=0.03, p=0.02). MIS-C and KDSS were more likely to have conjunctivitis compared to TSS and SS. CONCLUSION(S): MIS-C was found to have a lower WBC, lower sodium, lower ejection fraction, and required less fluid resuscitation. TSS had the highest VIS and had the highest INR. KDSS and MIS-C had more conjunctivitis and presentation than SS and TSS. KDSS had more oral and extremity changes compared to MIS-C.

Purpura Trombocitopenica Trombotica Pos-Covid-19

O objetivo deste relato de caso e disseminar, para a comunidade medica, o caso abordado, a fim de relacionar a purpura trombocitopenica trombotica e a COVID-19. Foi realizado um estudo observacional descritivo baseado na analise de um prontuario do caso de uma paciente internada no Hospital da UNIMED de Volta Redonda-RJ, onde as informacoes foram tratadas e analisadas, e, foram levados em conta os dados das condutas e das prescricoes realizadas no periodo da internacao. Mulher de 22 anos, deu entrada no pronto socorro com quadro de agitacao psicomotora de inicio subito, associado a relato de fala desconexa, com utilizacao de sedacao progressiva sem eficiencia. No exame fisico a paciente se encontrava confusa, levemente agitada, eupneica sob cateter nasal de O2, hemodinamicamente estavel, acianotica, levemente icterica, afebril, hipocorada, hidratada e sem deficit motor. A ausculta cardiovascular com ritmo cardiaco regular em dois tempos, bulhas normofoneticas, sem sopros ou extrassistoles. Foi monitorizada, apresentando taquicardia sinusal com frequencia cardiaca de 154bpm. Escala de coma de Glasgow de 14 pontos. Glicemia capilar de 131mg/dl. Sem evidencia de sangramento atipico. Exames laboratoriais: Hemacias 1.47milhoes/mm3, hemoglobina 4.7 g/dL, hematocrito 14.3%, VCM 97fl, plaquetas 9.000/mm3, reticulocitos 14,2%, creatinina 0.58, bilirrubina indireta 1,26mg/dl, haptoglobina <8 mg/dL, LDH 1228U/l, PCR <5 mg/dL, INR 1,23. As sorologias de Citomegalovirus, Epstein-Barr, Herpes, HIV, Hepatites A, B e C foram realizadas e com resultados inespecificos para a sintomatologia da paciente. Esfregaco de sangue periferico com presenca de esquizocitos(3+/4+). Tomografia de cranio normal, tomografia de torax com opacidades em vidro fosco nos segmentos pendentes dos pulmoes, um pouco mais evidente a esquerda, fina lamina liquida junto ao recesso pericardico superior. Apos 1 semana o teste rapido e o Swab nasal (RT-PCR) para COVID-19 foram realizados ambos apresentaram resultados negativos, porem a sorologia IgG para COVID-19 retornou reagente. Posteriormente foi realizado o exame de Perfil de atividade e inibidor da ADAMTS13, e pela baixa atividade do ADAMTS13 (<7%) e com o teste reagente para inibidores anti-ADAMTS13, pode-se confirmar o diagnostico de PTT. Foi transferida para a UTI, recebeu plasmafereses, pulsoterapia com metilprednisolona, posteriormente iniciou tratamento com Rituximabe ate evoluir com alta hospitalar. A PTT constitui um disturbio hematologico caracterizada pela oclusao disseminada na microcirculacao no qual as infeccoes em geral estao entre os principais fatores que desencadeiam o transtorno por meio da ativacao endotelial. A ocorrencia de uma infeccao previa por COVID-19 na paciente do caso corrobora a hipotese de que essa condicao hematologica esteja relacionada a uma complicacao da infeccao pelo coronavirus. A COVID-19 e uma das varias causas possiveis de PTT adquirida. A desregulacao imunologica causada pela infeccao tardia por SARS-CoV-2 pode ter precipitado esse disturbio hematologico. Mais estudos devem ser publicados para confirmar se de fato existe o fator causal entre essas duas condicoes. Copyright © 2022

The IDEAL (ISPAE diabetes education and learning) virtual pediatric diabetes educator training model is affordable and accessible in limited-resource settings. Can it be sustainable and replicable as well?

Introduction: Structured diabetes education (DE) is vital to manage pediatric diabetes (PD) but educators are scarce in developing countries. Due to familiarity with virtual teaching in the COVID pandemic, a virtual PDE course was planned for India. Objective(s): Evaluate outcomes of a virtual PDE course in a limitedresource (LR) setting. Method(s): A 9-member ISPAE (Indian Society for Pediatric & Adolescent Endocrinology) committee, with 47 experienced volunteer faculty planned a 12-week comprehensive curriculum (delivered in English, fee INR 5000 = US$65) basic & advanced skills: diagnosis, pathophysiology, insulin, SMBG, CGMS, CSII, MNT, exercise, psychology, toddlers, adolescents, type 1&2, other special situations: 17 teaching +5 feedback sessions, exit exam;practical assignments for each session. Result(s): Trainees working with T1D selected from across India: semiurban were preferred. Lengthy course with 90%-95% attendance (highly motivated) possible as no leave, travel, or stay costs needed. Easier for women to join. Significant rise in post-test scores that is, knowledge improved. Certification was based on stringent criteria. Other advantages: intense interaction, personal commitment, continued networking, and awareness of resources. Challenges: widely varied resource, language, and social settings: language barriers, limited resources, variable baseline knowledge. Conclusion(s): The IDEAL PDE training model being virtual & intensive is an affordable & accessible alternative to a physical program in LR settings. We hope to make it high quality, sustainable, and replicable.

Level of coagulation aberrations among COVID-19 patients in Ethiopia, Findings from the Horn of Africa

Background: Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19). Abnormal coagulation parameters in COVID-19 patients are important prognostic factors of disease severity. Aim(s): To analyze coagulation profiles of hospitalized COVID-19 patients in Addis Ababa, Ethiopia, the Horn of Africa. Method(s): This prospective cross-sectional study was conducted among 455 Covid-19 patients admitted at Millennium COVID 19 care and treatment center, Addis Ababa, Ethiopia from July 1-October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOTDUEPLUS coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p < 0.05 was defined as statistically significant. Result(s): A prolonged prothrombin time was found in 46.8% of study participants with COVID-19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients.Thrombocytopenia was detected in 22.1% of COVID-19 patients. 50.5% and 51.3% of COVID-19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. Conclusion(s): Inthisstudy, prolonged prothrombin time and elevated INR were detected in morethan 50% of severe and critical COVID-19 patients.Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients olderthan 55 years.Thus, were commendemphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID-19 patients.

Impact of the COVID-19 pandemic on anticoagulation control for patients using warfarin

Background: Patients on warfarin require regular international normalized ratio (INR) monitoring. The SARS-CoV- 2 pandemic may have substantially affected in-person medical visits and laboratory testing. However, it is not clear how warfarin monitoring practices have been affected by the pandemic, given the importance of tight INR control. Aim(s): To assess whether chronic warfarin management, as measured by INR testing frequency and time in therapeutic range (TTR), differed during the COVID-19 pandemic compared with the pre-pandemic period. Method(s): We identified all patients enrolled in an anticoagulation clinic associated with an urban academic medical between January 1, 2019 and May 31, 2021 with at least 2 INRs checked during this time period. We calculated frequency of INRs checked per month and TTR based on individual INR goals and compared the pre-pandemic (Jan 2019-Feb 2020) and pandemic (March 2020-May 2021) periods. INR frequency and TTR were modeled as a function of time period using Poisson and linear regressions respectively, accounting for repeated observations. Result(s): Of the 1052 patients included, 43.9% were women and average age was 66.3 years. Pre-pandemic, an average of 1.58 (95% CI 1.52-1.64) INRs were checked per month, as compared with 1.09 (95% CI 1.03-1.15) in the pandemic period (p< 0.001) (Figure 1). Average TTR per month was also calculated (Figure 2). On average, TTR was 56.8% (95% CI 54.9-58.8%) pre-pandemic compared to 39.4% (95% CI 37.5-41.5%) during the pandemic period (p < 0.001). (Table Presented) Conclusion(s): There was a significant decrease in the frequency of INR measurements as well as TTR during the pandemic. A number of factors may have contributed to this, including regulatory and logistical constraints on clinic and laboratory visits and patient anxiety about visiting medical facilities. Larger scale studies are warranted to further characterize pandemic effects on warfarin use and monitoring, as well as clinically significant outcomes of thrombosis and hemorrhage.

The immediate effect of COVID-19 vaccination on anticoagulation control in adolescents and young adults using vitamin K antagonists

Background: The European Medicine Agency has authorized COVID-19 vaccination in young adults from 12 years onwards. COVID-19 vaccination is associated with a negative effect on the quality of anticoagulation stability in adult vitamin K antagonists (VKA) users, due to an increased risk of supra-and subtherapeutic INRs after the first vaccination. It is unknown whether this effect is also observed in adolescents and young adults (AYA) using VKAs. Aim(s): To investigate whether the COVID-19 vaccine also affects anticoagulation stability in AYAs using VKA. Method(s): A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKA. INR results before vaccination, the reference period, were compared with the first INR after the first and, if applicable, second vaccination. Vaccination is deemed safe when the INR is <3.5. Anticoagulation clinics were encouraged to measure the INR within 2 weeks after vaccination. Result(s): Ninety-six AYAs were included, with a median age [IQR] of 25 [7] years, of whom 53.1% were female and 67.7% used acenocoumarol. The majority of AYAs (69.8%) received the BNT162b2 vaccine. [Table 1]. The percentage of INR results within range was significantly lower after the first vaccination (60/97 (62.5%) vs. 40/97 (41.7%), p = 0.004) due to an increase in supratherapeutic INRs (12/97 (12.5%) vs. 30/97 (31.3%), p = 0.005) [Figure 1]. The percentages of subtherapeutic INRs (24/97 (25.0%) vs. 26/97 (27.1%), p = 0.864) and INRs >=5 (1/97 (1.0%) vs. 2/97 (2.1%), p = 1.000) before and after first vaccination were similar. No differences were observed after the second vaccination compared to before or after the first vaccination. Complications after vaccination occurred less often than before vaccination (3.0 vs. 20.0, p = 0.012) and were non-severe. Conclusion(s): COVID-19 vaccination is also associated with a negative effect on anticoagulation stability in AYA VKA users, but not with an increase in complications. Still, it is advisable to monitor the INR shortly after vaccination.

A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Cefazolin-Associated INR Elevation: A Case Report.

PURPOSE: To describe a case of significantly elevated international normalized ratio (INR) in a patient on apixaban receiving treatment with intravenous cefazolin in the setting of coronavirus disease 2019 (COVID-19) infection and malnutrition. SUMMARY: A 74-year-old male patient on apixaban receiving cefazolin for osteomyelitis in the setting of COVID-19 and poor nutritional intake presented with internal jugular tunneled catheter site bleeding and an INR of greater than 22.5. Laboratory abnormalities and bleeding concerns were successfully managed with vitamin K and changing antimicrobial therapy from cefazolin to daptomycin. Follow-up labs one week later demonstrated a sustained improvement in coagulopathy. CONCLUSION: INR prolongation believed to be secondary to cefazolin can be effectively managed with administration of vitamin K and conversion of antimicrobial therapy to an alternative agent.

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

THAT BLOODY CLOT DOES NOT ALWAYS NEED A TUNNEL TO MIGRATE: A CASE OF MULTIPLE ARTERIAL AND VENOUS THROMBOSIS IN A COVID-19 PATIENT

SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Covid 19 virus has impacted nearly 450 million people across the globe;ranging from an asymptomatic carrier state to respiratory symptoms, cardiovascular symptoms, hematologic manifestations and multiorgan failure to death. Thrombotic events are one of its devastating complications. CASE PRESENTATION: A 66 year old man with a history of diabetes mellitus, hypertension and 30 pack years smoking history presented to the emergency room with hypoxia and altered mental status. On exam, his GCS was 8/15 and oxygen saturation was 85% on room air. He was subsequently intubated. CTA chest demonstrated bilateral diffuse ground glass opacities and left pulmonary embolism (PE). CT abdomen and pelvis showed multifocal infarcts in the right kidney with findings suggestive of renal artery thrombosis. Initial platelet count was 80,000/ul with creatinine of 3.9 mg/dl and creatine kinase (CK) of 3977 u/l. His INR was 1.4. Patient was not a candidate for thrombolysis given his thrombocytopenia. He was started on intravenous (IV) heparin and given IV hydration. On day 3 of his admission, he developed dry gangrene of the toes. Ankle brachial index of the right lower extremity (LE) was 1.16 and left LE was 0. Duplex ultrasonography of left LE showed mid to distal popliteal artery thrombus occluding below knee popliteal and tibial arteries. Echocardiogram showed ejection fraction of 55% and bubble study was negative for any intra atrial or pulmonary shunting. On day 4 of his admission, he developed oliguria and his gangrene got worse. His platelet counts decreased to 36,000/ul. Other pertinent labs showed INR 1.2, PT 15.3, PTT 34, D dimer 14.82, fibrinogen 498, CK 6434 mg/dl, hemoglobin 13.2 g/dl, haptoglobin 243 mg/dl and LDH 1041 U/l. Given his poor prognosis in the setting of ventilator dependent respiratory failure, multiple thrombosis and kidney failure requiring hemodialysis, the family decided to withdraw care. DISCUSSION: There are multiple hypotheses of thrombus formation in Covid 19 infection such as interleukin 6 and other cytokines induced endothelial injury, angiogenesis and elevated prothrombotic factors such as factor VIII and fibrinogen. Our patient had PE, renal artery thrombosis and popliteal artery thrombosis. Despite being on full dose anticoagulation, he developed gangrene of the toes. His lab results were not consistent with disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and he was not known to have any baseline hypercoagulable disorder. He did not have any intra cardiac shunts. Hence, it is most likely Covid 19 induced multiple arterial and venous thrombosis. CONCLUSIONS: The treatment of Covid 19 related thrombosis has become very challenging especially in the setting of multiple clots. It is crucial to have large multicenter studies to investigate vascular complications of Covid-19 and to formulate management strategies to ensure good patient outcomes. Reference #1: https://www.nejm.org/doi/full/10.1056/nejmoa2015432 Reference #2: https://journal.chestnet.org/article/S0012-3692(21)01126-0/fulltext DISCLOSURES: No relevant relationships by Devashish Desai No relevant relationships by Swe Swe Hlaing no disclosure on file for Jean Marie Koka;No relevant relationships by Hui Chong Lau No relevant relationships by Subha Saeed No relevant relationships by Anupam Sharma No relevant relationships by Muhammad Moiz Tahir

ACUTE HEPATIC SEQUESTRATION CRISIS: AN OFTEN UNDERDIAGNOSED AND FATAL SYNDROME

SESSION TITLE: Critical Renal and Endocrine Disorders Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Sickle Cell Disease (SCD) is an autosomal recessive disease characterized by an abnormal beta-globin chain of hemoglobin (Hb) that leads to malformed sickled cells with a multitude of downstream microvascular occlusions and anemia. While splenic infarction is by far the most common gastrointestinal (GI) manifestation, vaso-occlusion may occur in the liver, leading to an acute hepatic crisis. Acute hepatic sequestration of sickled erythrocytes is an exceedingly rare manifestation. CASE PRESENTATION: A 43-year-old man with homozygous sickle cell disease complicated by End-Stage renal disease was admitted with generalized malaise, right upper quadrant (RUQ) abdominal pain, nausea and vomiting. He was febrile with a temperature of 38.1°C, hypotensive with a blood pressure of 93/61 mmHg and tachycardic with a heart rate of 120 bpm. He was lethargic and uncomfortable with diffuse abdominal tenderness without guarding. Due to concern for septic shock, blood cultures, COVID PCR and influenza were obtained, and the patient was rapidly transferred to the intensive care unit for closer monitoring. Empiric vancomycin and cefepime were started promptly. The initial hemoglobin level was 6.1mg/dL with a leukocytosis of 31.2 K/CUMM and absolute neutrophil count of 21.8 K/CUMM;total hyperbilirubinemia of 17.45 mg/dL, direct hyperbilirubinemia of 11.46mg/dL and elevated INR at 1.66. Computed tomography of the abdomen and pelvis without contrast showed a known 4 cm cystic lesion of the right hepatic lobe and atrophic kidneys. Duplex flow of the abdomen and pelvis showed no portal vein thrombosis and patent flow in the portal vein and artery. Over the course of several hours, the patient's hemoglobin dropped to 3.8mg/dL with a steep rise in LDH and total bilirubin to 632 U/L and 27.04 mg/dL, respectively consistent with hepatic sequestration crisis. Patient was transfused with two units of packed red blood cells, fluid hydration and initiation of erythrocyte exchange transfusion. Prior to receiving exchange transfusion, the patient experienced rapid clinical deterioration with subsequent pulseless electrical activity. Return of spontaneous circulation was achieved transiently however patient's family at this point opted for palliative measures and the patient passed away shortly thereafter. DISCUSSION: Complications of SCD manifest in multiple organ systems. One of the few acute manifestations, hepatic sequestration crisis, is often unfamiliar to many clinicians and left unrecognized, results in poor clinical outcomes. It is rarely encountered and treatment options with blood and, more importantly, exchange transfusion remains often underutilized. CONCLUSIONS: Acute hepatic sequestration crisis is an often-unrecognized manifestation of SCD in which delay in diagnosis and prompt treatment with exchange and blood transfusions may impart a significant risk of mortality in an already prone patient population. Reference #1: Shah R, Taborda C, Chawla S. Acute and chronic hepatobiliary manifestations of sickle cell disease: a review World J Gastrointestinal Pathophysiology 2017;8(3): 108-116 Reference #2: Norris W. Acute hepatic sequestration in sickle cell disease. J of the National Medical Association 2004;96: 1235-1239 Reference #3: Praharaj D, Anand A. Sickle Hepatopathy J of Clinical and Experimental Hepatology 2021;11: 82-96 DISCLOSURES: No relevant relationships by Karim Dirani No relevant relationships by Georgiana Marusca No relevant relationships by Aryan Shiari

VACCINE-INDUCED THROMBOCYTOPENIA AND THROMBOSIS: SAILING CLOSE TO THE WIND IN A PANDEMIC

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Ever since the global introduction of adenovirus-vector COVID-19 vaccines, cases of cerebral venous sinus thrombosis and thrombocytopenia after immunization has been reported, posing a challenge to global effects on vaccine implementation. CASE PRESENTATION: A previously healthy 33 year old male presented to emergency room with altered mental status after a left sided seizure episode at home. Patient had a 1week history of occipital headache after receiving Ad26.COV2·S Johnson and Johnson vaccine 2 weeks prior. MRI showed superior sagittal sinus thrombosis and right high frontal hemorrhage 8.6x4.7x4.9 cm. CT angiography confirmed nearly occlusive thrombosis of superior sagittal sinus with extension to right transverse sinus. Noted to have a hemoglobin of 15, platelet count of 74000, PT/INR 16/1.2 and PTT of 28. Started on intravenous heparin and intubated for GCS of 4. Heparin was stopped due to supra therapeutic PTT of 200 overnight, drop in platelet count to 55 and hemoglobin to 13. Repeat ct head done for change in neurological exam of dilated right pupil, showed frontoparietal hemorrhage 9.3 cmx4.1 cm and 7 mm midline shift. Heparin was reversed with protamine and transfused 1 unit platelets prior to emergent decompressive craniectomy and thrombectomy. Heparin induced platelet antibody and SRA came back positive confirming vaccine induced thrombocytopenia and thrombosis. Treatment was initiated with argatroban and IVIG. Platelet count improved with no further propagation of thrombus. Patient underwent feeding tube and tracheostomy placement after 10 days due to prolonged ventilator weaning period and poor mental status. Patient's neurological status continued to improve significantly over subsequent months in acute rehabilitation facility with only residual left sided hemiparesis. Patient was successfully decannulated and anticoagulation switched to apixaban DISCUSSION: Possible pathophysiology is thought to be due to a trigger in spike protein production after biodistribution of adenovirus vaccine and a subsequent autoimmune response resulting in thrombosis. Similar to HIT, platelet consumption leads to thrombocytopenia and the continued platelet and monocyte activation increases thrombin generation, resulting in thrombosis. CDC advices to maintain a high suspicion of cases with symptoms that may indicate an underlying thrombotic event along with simultaneous thrombocytopenia. Heparin use is discouraged, unless HIT testing is negative. The International Society on Thrombosis and Hemostasis (ISTH), recommend considering non-heparin anticoagulants and high-dose intravenous immunoglobulin (IVIG). While platelet transfusions are avoided, rapid progression with rising ICP may necessitate transfusion to enable neurosurgical intervention CONCLUSIONS: Management of complications including seizures and elevated intracranial pressure (ICP) is essential to reduce morbidity and mortality risk. Reference #1: Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384:2092–101. Reference #2: Muir KL, Kallam A, Koepsell SA, Gundabolu K. Thrombotic thrombocytopenia after Ad26.COV2.S vaccination. N Engl J Med 2021;384:1964–5 Reference #3: Pavord S, Scully M, Hunt BJ, et al. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. N Engl J Med 2021;385:1680–9 DISCLOSURES: No relevant relationships by Axel Duval No relevant relationships by Nadish Garg No relevant relationships by ARCHANA SREEKANTAN NAIR