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Objectives: To assess the immunological [Lymphocyte populations (LP) and Autoantibodies (Ab)] and clinical profile of rheumatoid arthritis (RA) patients who suffered from COVID-19 compared with non-COVID-19 RA patients. Method(s): A nested case-control study of RA patients treated under a strict follow-up model. RA patients and confirmed COVID-19 infection (last 24 months) and RA patients without the infection were included. Subgroups of cases: Long COVID (LC): symptoms after infection for >=4 weeks;Post COVID syndrome (PCS): symptoms for >=12 weeks;and patients with symptoms alpha4 weeks. Sociodemographic, clinical, and paraclinical variables of RA and COVID-19 infection (in cases) were captured. Antinuclear antibodies (ANA), anticardiolipin antibodies, lymphocyte populations (BD FACSDuetTM-BDFACSLyricTMmultiparameter flow cytometry) T cells, B cells, and NK were evaluated. Univariate and bivariate analyzes (STATA 17) were done. Result(s): 300 patients were included (148 cases/152 controls;87.3% women). Median age 59 years (IQR 11). 71.86% were in low disease activity. There were no significant differences in sociodemographic and clinical characteristics between cases and controls. Cases had a time since infection of 18.5 months (IQR 7). Of the total cases, 69%presented LC and 63%PCS.No significant differences were found between cases and controls in the lymphocyte population nor in the antibodies evaluated. There were no differences in the immune profile when comparing patients with LC and PCS with those with symptoms alpha4 weeks after COVID-19 infection. Conclusion(s): No differences were found in the behavior of the immunological profile (independent of symptoms of LC and PCS) in RA patients under strict follow up, evaluated long-term after infection with those who did not have COVID-19. This suggest that patients returned to their baseline homeostatic state, something that has not yet been reported up to now. These results should be replicated in populations with different RA characteristics.
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Background: Excessive activation of coagulation causing thrombotic complications was observed during Covid-19 infection. The objective of this study was to evaluate the frequency of antiphospholipid antibodies (aPL) in a group of patients with this infection. Method(s): 45 patients (10 Women and 35 men) diagnosed with SARS Cov2 infection were included in our study. The mean age was 63 +/- 10.7 years. Moderate, severe and critical forms were noted in 7%, 51% and 42% of patients, respectively. The IgG/IgM antibodies anti beta2 glycoprotein 1 (beta2 GP1) and IgG/ IgM anti cardiolipin (aCL) were assessed by an immuno-enzymatic assay (ELISA). Result(s): IgG, IgM anti beta2 GP1 and IgG, IgM aCL were positive in respectively 20%, 10%, 25% and 9% of patients. Stratification according to the form of infection showed a positive APL in 66%, 22% and 32% of moderate, severe and critical forms. Also, these APL were positive in 37% of deceased patients versus 23% of stable patients. Conclusion(s): The positivity of aPL appears to be high in our study. Early and effective anticoagulant treatment in Covid-19 patients is needed to avoid any complications.
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Protein S is a multifunctional plasma protein, whose deficiency, results in a rare congenital thrombophilia, inherited in an autosomal dominant pattern. It can aggravate the hypercoagulable state of pregnancy, when it presents in parallel with the condition, leading to adverse maternal outcomes and foetal loss. A 35-year-old female third gravida having previous 2 deliveries by Lower Segment Caesarean Section (LSCS) presented to emergency at 10 weeks pregnancy with chief complaints of pain and swelling in left thigh since 4-5 days. After thorough investigations and work-up, the patient was diagnosed with Protein S deficiency. She was managed conservatively and was delivered by elective LSCS with bilateral tubal ligation at 38 weeks of gestation with good foetal and maternal outcomes.The rarity of Protein S deficiency along with the successful outcome of the pregnancy makes this a unique case.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.
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Myocarditis can lead to myocardial infarction in the absence of coronary artery obstruction. We report a case of probable myocarditis, complicated by myocardial infarction with non-obstructive coronary arteries. A 19-year-old man presented with chest pain typical of myocarditis. He was a smoker but was otherwise well. Electrocardiogram revealed diffuse ST-elevation and echocardiography revealed a thin, akinetic apex. Troponin-T levels on admission were raised leading to an initial diagnosis of myocarditis being made. However, late gadolinium enhancement study on cardiac magnetic resonance imaging demonstrated transmural enhancement typical of ischaemia. Coronary angiogram was normal, leading to a likely diagnosis of myocardial infarction with non-obstructive coronary arteries. It is important to highlight that coronary assessment remains important when working up for myocarditis, as myocardial infarction with non-obstructive coronary arteries can often complicate myocarditis in cases of normal angiography. Another important lesson was on how cardiac magnetic resonance imaging provided vital evidence to support underlying ischaemia despite normal coronary angiogram, leading to a diagnosis of myocardial infarction with non-obstructive coronary arteries. Myocardial infarction with non-obstructive coronary arteries remains a broad 'umbrella' term and cardiac magnetic resonance imaging, as well as more invasive coronary imaging techniques during angiography, can further assist in its diagnosis. Our case provides a reminder that myocardial infarction with non-obstructive coronary arteries, although increasingly recognised, remains under-diagnosed and can often overlap with peri-myocarditis, highlighting the need to employ multi-modality imaging in guiding management.Copyright © The Author(s) 2021.
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Background: This study was aimed to find the correlation of anti-phospholipid antibodies in the risk of coagulopathy and disease severity in coronavirus disease-19 (COVID-19). Method(s): Clinical and laboratory findings were obtained from 50 confirmed COVID-19 patients hospitalized in Saiful Anwar General Hospital, Malang, Indonesia from September to November 2020. Anti-phospholipid antibodies were measured by finding of IgM anti-beta2 glycoprotein, lupus anticoagulant and IgM anti-cardiolipin. Clinical Symptoms, thrombotic events, and mortality during hospitalization were recorded. Disease severity was defined by COVID-19 Treatment by multi-departement guidelines, Ministry of Health, Year 2020, Indonesia. Result(s): Among 50 patients, 5 patient (10%) were positive of IgM anti-beta2 glycoprotein (2%), IgG anti-cardiolipin (2%) and IgM anti-cardiolipin (8%). Anti-phospholipid antibodies were associated with anosmia OR 8.1 (1.1-57.9) (P = 0.018), nausea and vomiting OR 12.4 (1.2-122.6) (P = 0.010), diarrhea OR 9.8 (1.3-70.9) (P = 0.010), cardiovascular disease OR 1.4 (1.0-1.9), (P = 0.001), chronic kidney disease OR 12.0 (1.6-90.1) (P = 0.05), acute coronary syndrome (P = 0.001), moderate OR 0.11 (0.01-1.1) (P = 0.031) and severe OR 18.5 (1.8-188.4) (P = 0.002) disease severity, and in-hospital mortality OR 8.1 (1.1-57.9) (P = 0.018). Conclusion(s): In conclusion, anti-phospholipid antibodies show a low prevalence in COVID-19 patients and are associated with increased risk of acute coronary syndrome, clinical manifestations, disease severity, and mortality. Anti-phospholipid antibodies in COVID-19 patients are mainly directed against anti-cardiolipin.
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Introduction/Background: Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary (occurring alone) or secondary (in combination with another disease, most commonly systemic lupus erythematosus (SLE)). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae. Description/Method: 13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9;initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the postretinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations (brain, spine MRI/MRV/MRA) concluded if patient developed new APSrelated symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects. Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal;increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-termanticoagulation. Discussion/Results: APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity. ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected lin to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti- B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.
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Background: Disseminated infections such as tuberculosis are known to result in a systemic inflammatory response leading to thrombosis, with increasing reported cases of thrombotic event being observed in patients infected with covid-19. This is the first reported case on co-infection with COVID-19 pneumonia and disseminated tuberculosis causing catastrophic antiphospholipid syndrome (CAPS). Method(s): The report highlighted the challenges in the diagnosis and management which include the use of corticosteroid in setting of systemic infections. Another diagnostic dilemma was to explain the cause of myositis by tuberculous or autoimmune. Case Presentation: We report a 26-year- old man with HbE trait thalassemia who reported unintentional weight loss, night sweats for 1 month prior to the diagnosis of covid-19 infection on 10th March 2022. Seven days later, he was hospitalized for suspected perforated appendix. Computed tomography (CT) abdomen revealed hepatosplenomegaly, prostatitis, seminal vesiculitis. Multiple matted abdominal lymph nodes were not amenable for biopsy. Soon, he appeared toxic, dyspneic required non-invasive ventilation with bilateral parotitis. He had raised erythrocyte sedimentation (ESR) 52 mm/hour, C-reactive protein (CRP) 221 mg/dl, lactate dehydrogenase (LDH) 730U/L. Direct Coomb's antibody was positive but did not have any form of haemolysis. Complement 3 (0.45 g/L) and complement 4 (0.1 g/L) levels were low. Serum IgG4, procalcitonin, anti-nuclear antibody, cultures and virology were negative. Sputum for acid fast bacilli (AFB) was positive on Auramine O stain but the Ziehl-Nelson (ZN) stain and tuberculous PCR (GeneXpert) were negative. Diagnosis of disseminated tuberculosis was made but his abdominal pain persisted despite being on anti-tuberculous therapy (ATT), and he had new evidence of splenic infarct. CT angiogram also revealed celiac trunk and superior mesenteric artery thrombosis. Antiphospholipid (aPL) test was positive for lupus anticoagulant, beta 2 glycoprotein 1 and anti-cardiolipin antibodies. Therapeutic anticoagulation and plasma exchange were initiated for probable CAPS followed by intravenous immunoglobulin and corticosteroid. Thereafter, the patient developed severe bilateral pelvic girdle pain with evidence of myositis on the MRI (Figure 2). Serum creatine kinase was never elevated. Anti-PL- 7 and anti Ro-52 were borderline elevated. He recovered well and ambulant before discharged home. Conclusion(s): Our case highlight the complexicity of presentation of CAPS who manifested as multiple arterial thrombosis. The diagnosis of disseminated tuberculosis relied strongly on microbiological, imaging and clinical presentation as histopathological evidence was not feasible. Management challenges were deciding on corticosteroid in disseminated infection and the need for confirmation of persistent positive aPL test and to monitor myositis symptom to help guide decision making. (Figure Presented).
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Introduction/Background: Primary bone marrow oedema syndrome is an elusive and less well-defined entity. Whether Rheumatologists should consider it as a stand alone diagnosis, is debatable. It possibly would be best described as an MRI feature which could be a finding in a number of diseases which would include the initial phases of Osteonecrosis of the bone, Rheumatoid Arthritis, Spondyloarthritis, Enthesitis related, Post traumatic, OA, Infections and Cancers. The treatment options become constricted due to the paucity of evidence. Rheumatologists need to consider this as an area of unmet need with development of consensus classification criteria and treatment approaches. Description/Method: 27-year-old male, Height 174 cms Weight 90 Kgs BMI 29 Kg/m2, became symptomatic in Jan 2022 with complains of pain in the both hip joints & groin regions, pain became excruciating and he became bed-bound, with early morning stiffness lasting approximately 45 mins. Had received steroids for COVID infection in August 2020. Investigations Hb 13.5gm/dl TLC 7000/mm3 Platelet 400 x 103/mm3 Sr Bil 0.8mg/dl AST 16 IU/L. ALT 24 IU/L Sr Creatininine 1.1mg/dl Blood Sugar Levels, Fasting 89 mg/dl Post Prandial 102 mg/dl ESR 10mm in 1st hour by Wintrobes method CRP Quantitative 29.38mg/L HLA B27 by PCR Negative, RF Negative, ACCP Negative Serum, IgG, Beta2 Glycoprotein 1.44 SGU Serum, IgM, Beta2 Glycoprotein 3.44 SGU Serum, IgG, Cardiolipin antibody 8.4 GPL Serum, IgG, Cardiolipin antibody 17.45 GPL Lupus anticoagulant by DRVVT Negative Sr Cholesterol 211mg/dl HDL 29 mg/dl LDL 156mg/dl TGs 130 mg/dl MRI Hips & SI joints Transient bone marrow oedema/osteopenia of bilateral hip. PET CT Increased metabolic activity in both hip joints Bone Scan (99mTcMDP) Increased vascularity in perfusion phase, increased accumulation in soft tissue in blood pool phase and increased uptake in bilateral Hip joints in skeletal phase scan, suggestive of CRPS Type-I. Management Was initially managed with Tab Etoricoxib 90mg BD, also started on Tab Sulphaslazine and Tab Methotrexate. However, when he had no symptomatic relief he was administered Inj Infliximab on 12 May 2022 and a second dose on 9 June 2022. He had excellent pain relief after the 1st dose, however after 10 days of the administration, he again began experiencing pain especially after walking. He also had pain in the knees on this occasion. He was also administered Inj Zoledronic 4mg on 23 May 2022. He is at present not requiring any NSAIDs over the last 1 month. Discussion/Results: The patient having presented with excruciating and debilitating pain was worked up and evaluation revealed features of bone marrow oedema on MRI which was corroborated with bone scan and PET CT imaging. The acute phase reactant CRP was also significantly elevated. The patient also gave history of early morning stiffness lasting approximately 45 mins. Hence an underlying Inflammatory process such as Spondyloarthritis(Peripheral) with enthesitis was considered. The confounding factors were the pain which worsened on mobilization, HLA B27 negative status, Rheumatoid Factor and ACCP negative status and past history of having received IV Corticosteroids for COVID infection in August 2020. In view of the debilitating pain and aworking diagnosis of Spondyloarthritis, hewas started onNSAIDs alongwith rest, initially, followed by conventional synthetic disease modifying agents in Rheumatic disease followed by biologic synthetic diseasemodifying agent - Inj Infliximab. The thought process was to avoid prolonged NSAID use to prevent the associated side effects. However, since Avascular Necrosis of the Femoral head is a very likely possibility, the patient is planned to be kept under close follow up. Key learning points/Conclusion: Collaborative efforts between the Departments of Nuclear Medicine, Radiology, Orthopaedics and Rheumatology are crucial in the early detection and approach to cases of Bone Marrow oedema. Avascular necrosis of head of Femur is a far more common entity and must be kept in ind even when a diagnosis of Bone Marrow oedema syndrome is being entertained. Diagnosis of Bone Marrow oedema syndrome must be entertained only as a diagnosis of exclusion. Continued follow up and regular imaging must be pursued rigorously in patients diagnosed with Bone Marrow oedema syndromes. There is a requirement to document acute phase reactants such as CRP and ESR in patients diagnosed with Avascular necrosis of bone as this data could help us differentiate AVN from Primary Bone marrow oedema in the early stages.
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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
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SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumonia is a common condition that is seen in hospitals. Pneumocystis Jirovecii is an opportunist fungal pathogen. Bordetella bronchiseptica is a gram negative bacteria that causes infectious bronchitis in dogs and other animals, but rarely infects humans. CASE PRESENTATION: Patient is a 34 year old African American female with history of sickle cell trait, reported Lupus (not on treatment), asthma, COVID pneumonia who was admitted for worsening shortness of breath & productive cough with yellow sputum. She was previously hospitalized and discharged after being treated for Community-Acquired Pneumonia. In the ER, she was febrile, tachycardic, tachypneic, & hypoxic requiring BiPAP. CXR obtained showed findings concerning for multifocal pneumonia. Chest CT Angiogram was negative for PE. Patient was started on Vancomycin & Meropenem for treatment of her pneumonia. Blood cultures, Legionella, Strep pneumoniae, Aspergillus, Beta-D-glucan, Sputum culture, & MRSA screen were ordered for further evaluation of her infection. ANA screen reflex panel, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies were also ordered given patient's reported history of SLE and the concern for SLE pneumonitis: ANA & Sjogren's Anti-SSA were positive;otherwise, autoimmune workup was unremarkable. During hospitalization, patient was eventually weaned down to nasal cannula and antibiotic was de-escalated to levaquin. However, sputum culture eventually grew Bordetella Bronchiseptica that was resistant to Levaquin so antibiotic regimen was switched to Doxycycline. In addition, Beta-D-glucan was noted to be elevated. Bronchoscopy was done for further evaluation;multiple transbronchial biopsies were positive Pneumocystis Jirovecii. Patient was then initiated on Bactrim for treatment of PJP Pneumonia along with a steroid taper. Patient was tested for HIV and it was negative. DISCUSSION: In this case, patient was found to have two rare pathogens, that are more common in immunocompromised patients such as those with HIV/AIDS, on high-dose corticosteroids or malignancy. This patient had a unconfirmed diagnosis of SLE and past COVID Pneumonia. Patient had Bordetella bronchiseptica pneumonia that is frequently isolated in the respiratory tract of animals but can cause severe respiratory infection in humans. This microorganism can cause upper respiratory tract infections, pneumonitis, endocarditis, peritonitis, meningitis, sepsis and recurrent bacteremia. Upon further discussion with the patient, she was found to have a recent pet dog. CONCLUSIONS: High level of clinical suspicious is needed in patient presenting with recurrent pneumonia with chest imaging findings suggestive of multifocal pneumonia. The mainstay of treatment for PJP is TMP-SMX and steroid. We recommend Fluoroquinolones or tetracycline for Bordetella bronchiseptica pneumonia. Reference #1: Benfield T, Atzori C, Miller RF, Helweg-Larsen J. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr. 2008 May 1;48(1):63-7. Reference #2: de la Fuente J, Albo C, Rodríguez A, Sopeña B, Martínez C. Bordetella bronchiseptica pneumonia in a patient with AIDS. Thorax. 1994 Jul;49(7):719-20. doi: 10.1136/thx.49.7.719. PMID: 8066571;PMCID: PMC475067. DISCLOSURES: No relevant relationships by Priya George No relevant relationships by ELINA MOMIN No relevant relationships by Mohammedumer Nagori
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Background: Thrombosis is a unique complication in coronavirus disease 2019 (COVID-19). We have reported that elevated ferritin and D-dimer on admission were the risk factors of thromboses by analyzing the patients sequentially admitted to our hospital due to COVID-19 (1). However, we have not analyzed throm-botic complications in the view of the antiphospholipid antibodies (aPLs), which are frequently detected in the COVID-19 patients. Objectives: To elucidate the thrombogenic effects of aPLs in COVID-19, we analyzed the development of thrombosis in three lupus models after SARS-CoV-2 infection. Additionally, we evaluated the association of thrombotic events and the serum profile of aPLs in Japanese patients with COVID-19. Methods: Three animal models of lupus (MRL-lpr/lpr, NZBxNZW F1 and NZW×BXSB F1) were evaluated in this study. NZW×BXSB F1 was also considered as a model of antiphospholipid syndrome (APS) since aPLs were detected with a high titer (2). Experimental SARS-CoV-2 infection was induced using mouse-passaged virus strain (3). The incidence of thromboses in the lungs and kidneys were identifed by evaluating H&E staining and PTAH staining of paraf-fn-embedded sections. We have experienced 44 thrombotic events in 34 out of 594 patients admitted to our institute. As a non-thrombotic COVID-19, 68 patients were selected to make a 1 to 2 matched-pair based on the propensity score. In total 102 patients, seven types of aPLs (anti-cardiolipin (CL) IgG/IgM, anti-β2GP1 IgG/IgA/IgM, and anti-phosphatidyl serine/prothrombin complex (PS/PT) IgG/IgM) were measured using specifc ELISA kits. The patients' clinical characteristics and serological profile of aPLs were further evaluated. Results: We identifed the development of thromboses in the lungs or kidneys in 6 out of 12 (50%) NZW×BXSB F1 mice after the SARS-CoV-2 infection, whereas no thrombosis was observed in non-infected mice. Further, there was no thrombosis in the other lupus models (0%) after the infection. These fndings might suggest the pathogenic role of aPLs under the SARS-CoV-2 infection. Among our COVID-19 patients, 39 out of 102 (38%) were tested positive for one or more aPLs. The positive ratios of any aPLs were statistically indifferent between the patients with or without thrombosis;anti-CL IgG (8.8% vs 5.9%)/IgM (0% vs 5.9%), anti-β2GP1 IgG (21% vs 12%)/IgA (8.8% vs 15%)/IgM (0% vs 1.5%), and anti-PS/PT IgG (0% vs 2.9%)/IgM (12% vs 13%), respectively. In addition, their titers were relatively lower than those observed in APS patients. The patients' characteristics and the prognosis of COVID-19 were comparable regardless of the detection of any aPLs. These fndings suggested that COVID-19 associated aPLs were irrelevant to thrombotic complications. Conclusion: Thromboses were induced after the infection of SARS-CoV-2 only in the APS model. However, aPLs detected in COVID-19 patients have little impact on the development of thrombosis. SARS-CoV-2 infection might have a high risk of thrombosis, especially in APS patients, as shown in the case report (4). The discrepancy of its thrombogenic effects of aPLs might be explained by the low titer of the antibody or the diversity of antibody epitope. Further analyses are required to clarify the mechanisms of aPLs production and the development of thrombosis in COVID-19.
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Introduction: Evidence regarding thrombotic microangiopathy related to covid-19 is reported in the literature, particularly in severe cases. We describe a case recovered from previous asymptomatic covid-19, presenting with acute renal failure, hemolytic anemia, and low platelets. Thrombotic microangiopathy (TMA) was confirmed by renal biopsy, without immunofluorescence staining for C3c and C1q, suggesting this case is not complement-mediated. Anticoagulant therapy led to kidney function improvement. Methods: Case report. Results: A 72-year-old women with a past medical history of primary hypertension was referred to the hospital for the diagnosis of acute renal failure. Three days prior to admission, she suffered abdominal pain, decreased urine output, her blood test revealed elevated serum creatinine of 393 umol/L, and low platelets of 43.6 K/uL. She denied history of hematologic or renal disorders, yet mentioned that she found asymptomatic covid-19 one month before admission. On admission, the vital signs was significant for a blood pressure of 140/80 mmHg. Physical examination was noted with facial oedema, upper abdominal pain, otherwise unremarkable. Laboratory test confirmed acute renal failure with the ongoing increase of serum urea 30.4 mmol/L and creatinine 575 umol/L. Her total blood count discovered thrombocytopenia and anemia, with the platelet count of 50 k/uL, and the hemoglobin of 94 g/L. Lactate dehydrogenase was in upper limit of 434 U/L, and the bilirubin level was in normal range. The peripheral blood smear showed “fragmented” RBCs. Coombs’ test was negative for both direct and indirect method. Stool examination failed to detect either red or white blood cell. Haptoglobin level was 1.14 g/L, which was in normal range (0.41-2.58 g/L). Ddimer was elevated 1376 ng/mL, and the fibrinogen 6.37 g/L. Immunology investigation was conducted with the result of normal level for both complement C3 and C4, negative reaction for anti-cardiolipin IgM and IgG, anti MPO, anti PR3, RF, anti-streptolysin O. Bone marrow aspiration did not show abnormalities. There were Forrest III gastric ulcers found by gastric endoscopy (two ulcers with diameter of 9mm and 10mm, with pseudo-membrane covered). Initially she was treated symptomatically with amlodipin, intravenous PPI, and IV furosemide. As the kidney function was getting worse, hemodialysis was initiated at day 1, day 3, day 6, and day 10 of admission. Renal biopsy was performed and showed active thrombotic microangiopathy. Given the normal complement profile, and negative C3c staining on immunofluorescence of renal biopsy investigation, complement mediated TMA may not be the pathogenesis of this case. The patient was started for anticoagulant therapy, initially subcutaneous low molecular weight heparin and then oral anti-vitamin K. She obtained dramatic recovery with dialysis off, increased urine output, normalized platelets and red cell count, and serum urea and creatinine back to nearly normal range at discharge. Conclusions: Complement related thrombotic microangiopathy is a rare and severe condition. This case of TMA after covid-19 reveals a non-complement mediated pathogenesis, with different treatment. Anticoagulation is an effective therapy in hypercoagulation induced TMA. No conflict of interest
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Introduction: Systemic lupus erythematosus (SLE) is a rare diagnosis in children and can present with nonspecific symptoms. Similarly, arterial thromboses in children without risk factors is also rare. Together, they present a diagnostic challenge which may lead to a delay in proper management. Our objective is to emphasize the importance of having high suspicion for SLE in children, especially when presenting with arterial thrombosis. Case Description: Our patient is a 6-year-old female who presented with a 3-week history of severe right foot pain with a 1-week history of discoloration in the same foot. She sought care multiple times prior to presentation. She initially received the diagnosis of “COVID toes” despite a negative COVID PCR. Prior to presentation, she developed fevers, worsening foot pain, increasing discoloration, decreased oral intake, weight loss, and fatigue. Further lab work showed acute kidney injury, elevated inflammatory markers, and coagulopathy. She was also found to have elevated troponins and QTc prolongation. Additionally, a lower extremity Doppler demonstrated an acute partially occluding thrombus in her right popliteal artery. She was transferred to the pediatric intensive care unit (PICU) and started on a heparin infusion. An Echocardiogram with bubble study showed no interatrial shunting. Thrombolysis was considered but held due to concerns regarding thrombus chronicity. COVID-19 PCR and antibodies were negative, so Infectious Disease team determined this was unlikely related to an acute or remote COVID-19 infection or multisystem inflammatory syndrome in children (MIS-C). Her hemoglobin and platelets began to downtrend and Coombs was positive, raising concern for autoimmune hemolytic anemia. Autoimmune and coagulopathy work-up was significant for positive ANA titer, low complement levels and elevated anticardiolipin, anti-dsDNA, anti-Smith, anti-chromatin, and anti-RNP antibodies. She also had a chest X-ray that showed small non-infectious pleural and pericardial effusions suggestive of serositis. The constellation of these findings eventually led to the diagnosis of SLE. Discussion: There have been several cases of thrombotic or thromboembolic events reported in pediatric patients with SLE, with a majority being venous related events. Only two reports involving cerebral arteries have been published. For several of these patients, thrombosis was the presenting symptoms of their disease. In our literature review, we did not find any cases of arterial thrombosis outside the central nervous system related to SLE. Conclusion: Arterial thrombosis can be a presenting symptom for SLE in children. Despite being a rare presentation, rheumatologic diseases such as SLE should always be considered to prevent a delay in diagnosis and management. In our case, our patient experienced a notable delay in care due to a misdiagnosis related to the COVID-19 pandemic. While it is extremely important to consider sequelae of COVID-19, we would like to emphasize the importance of ensuring consideration of other diagnoses as well.
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COVID-19 infection predisposes patients to a hypercoagulable state. The clinical significance of concomitantly positive antiphospholipid antibodies as a risk factor for thrombus formation is unknown. We report a case of renal infarct secondary to COVID-19 infection with mildly elevated antiphospholipid antibodies. A 71-year- old woman with a history of hypertension, supraventricular tachycardia, resected carcinoid tumor in remission, COVID-19 infection (20 days prior), presented to the hospital with acute onset severe left lower quadrant pain radiating to the left flank for one day. She reported a fever of 101 F. Vital signs were normal in the emergency room. Physical exam showed left costovertebral angle tenderness, otherwise benign abdomen with no guarding or rigidity. Laboratory findings showed normal liver function tests, mildly elevated creatinine at 1.1 mg/dl (baseline 0.8 mg/dl), and leukocytosis (14.2 K/ul). Urinalysis showed no evidence of proteinuria or microscopic hematuria. CT scan of the abdomen demonstrated a large area of patchy hypoattenuation involving the upper pole and interpolar region of the left kidney with adjacent perinephric inflammation representing a sequela of an infarct. Hypercoagulable workup including HIV, hepatitis, ANA, ANCA, complements, B2 glycoprotein, homocysteine, factor V Leiden, anti-thrombin III, protein C, protein S were done. All tests resulted negative except for mildly elevated anticardiolipin antibody, IgM 12.90 MPL (normal 0.00-12.49 MPL). Holter monitor was negative for atrial fibrillation. An echocardiogram did not show any thrombus. Considering her negative tests, renal infarct was believed to be secondary to a hypercoagulable state from COVID-19 infection. Antiphospholipid antibodies repeated 3 months after this admission were mildly elevated. Renal infarction was treated with a heparin infusion and was subsequently transitioned to apixaban. Acute kidney injury resolved with intravenous fluid resuscitation. At a 3-month follow-up, her renal function remained stable with a resolution of symptoms. Renal artery infarct is a possible thrombotic complication of COVID -19. Role of lupus anticoagulant antibodies in increasing this risk warrants further studies.
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The article describes a COVID-19 patient with several biomarkers of systemic cytokine storm (including multiple excess over the reference values of C-reactive protein, ferritin and D-dimer) and increased level of autoantibodies (aPL and anti-CCP). At the same time contrast-enhanced CT and US failed to detect pulmonary embolism or lower limb deep vein thrombosis. Three months after discharge from the hospital, a high level of antiphospholipid antibodies and D-dimer remained. The relationship between infection with SARS-CoV-2 and autoimmunity has been discussed.
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Background: Infections, drugs, surgical procedures, blood transfusions, solid and hematological cancers, and autoimmune disorders are associated with the risk of developing acquired FV inhibitors. Case report presentation: A 66-year-old Caucasian woman presented to the Emergency Department because of recurrent episodes of bowel bleeding from 2 week, and bleeding from the sites of venous sampling. Coagulation tests showed that the platelet count was normal: prolonged prothrombin time (PT): 45.5 seconds, international normalized ratio: 4.03, and activated partial thromboplastin time (aPTT): 165 seconds, aPTT ratio: 5.4. Coagulation factor II (FII), factor X (FX), factor VIII (FVIII), and fibrinogen were normal. The FV activity was 0.2% (range of normality 60-120%). The PT, aPTT, and one-stage coagulation factors assays were performed using an ACL TOP 550 coagulometer, and factor V was determined using a onestage PT-based assay, and factor V-deficient substrate plasma. Anticardiolipin antibodies were negative. Mixing test of patient's plasma with normal pooled plasma revealed the existence of an FV inhibitor, with an activity level of 4.0 Bethesda unit/mL. Three weeks before, the patient had been treated for coronavirus disease 2019 (COVID- 19) at home, with steroids (dexamethasone 6 mg daily for 5 days), enoxaparin 4,000 IU daily, and oxygen. Conclusions: The Authors presented a case report with acquired factor V inhibitor after SARS-CoV2 disease.
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Introduction: Since the appearance of the first patients infected by COVID 19;Multiple cases with haemostasis disorders have been reported, both in deceased and critically ill patients, evidenced by the presence of clots and thrombosis events at different levels. Despite this, it is unknown whether this activation of coagulation prevails in patients after their recovery. Objective: To determine alterations in hemostasis in convalescent adult patients from COVID-19. Methods: An observational, descriptive, retrospective, cross-sectional study was carried out in 43 convalescent patients. Prothrombin time, activated partial thromboplastin time, clot retraction, platelet count, fibrinogen, anticardiolipin antibodies, lupus anticoagulant, plasminogen activator inhibitor 1 and tissue plasminogen activator. Results: Prolonged PT was found in 2 patients, shortened PTT in 4 and prolonged in 1, non-retractile clot in 8 patients, thrombocytosis in one and increased fibrinogen in 15. In 86 % (n = 37) the presence of LA and ACA in 7 patients, PAI 1 elevated in 18.6 %, tPA increased in 34.9 %. The presence of LA predominated in patients with care and complications. Conclusions: After the acute period of infection, some parameters of hemostasis remain elevated, which is possibly related to the underlying inflammatory process.
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Background. Patients who are hospitalized with Coronavirus 2019 (COVID-19) are known to have increased risk for thrombosis. Several mechanisms have been proposed for increased thrombogenesis, including antiphospholipid antibodies (APLs). We sought to better understand the relationship between a commonly used marker of thrombosis, D-dimer, and antiphospholipid antibodies in relation to thrombosis in COVID-19. Methods. This was a single-center prospective cohort study. Participants were adults admitted to the hospital with COVID-19 between March and December of 2020. Included patients required a positive COVID-19 nasopharyngeal nucleic acid amplification testing (NAAT), coagulation studies, and regular assessment of D-dimer levels. Patients who were excluded were pregnant adults, use of oral anticoagulants prior to admission, and absence of a positive COVID-19 nasopharyngeal NAAT. We tested 52 patients for antiphospholipid antibodies (APLs), including lupus anticoagulant (LA), anti-beta-2 glycoprotein antibodies (B2GP), and anti-cardiolipin antibodies (aCL). The endpoint for analysis was hospital discharge or development of a confirmed thrombosis. Results. Twenty-nine of fifty-two patients (55.7%) with COVID-19 had non-negative APLs. Of these patients, twenty-seven (93.1%) had non-negative aCLs, the majority of which were IgM antibodies. There was a total of 7 thrombotic events in our cohort. The sensitivity of D-dimer alone was 85% and the sensitivity of APLs alone was 71%. In patients with an intermediate D-dimer level (i.e., greater than 2 milligrams per liter (mg/L) but less than 5 mg/L), the addition of non-negative APLs increased the sensitivity of D-dimer to 100%. In patients with a high D-dimer (i.e., greater than 5), the combined sensitivity of D-dimer and APLs was 60%. Out of the 7 thrombotic events in our cohort, two patients had negative APLs, however both patients had a D-dimer of greater than 5 mg/L. Conclusion. The use of APLs can assist in risk-stratifying patients in an intermediate-risk D-dimer group to consider prophylactic anticoagulation if APLs are negative and to consider therapeutic anticoagulation if APLs are non-negative. In the high-risk group (i.e., a D-dimer greater than 5 mg/dL), a therapeutic anticoagulation approach may be more appropriate.
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Introduction: Coagulation abnormalities leading to arterial and venous thrombotic events have been described in patients with COVID-19 and studies have reported an overall pooled incidence of venous thromboembolism (VTE) of 17%, however little is known regarding VTE association with antiphospholipid antibodies in patients with COVID-19.Hypothesis: Antiphospholipid antibodies are associated with VTE events in COVID-19. Methods: This is a retrospective cohort study of COVID-19 patients hospitalized at the University of Virginia Medical Center (UVA). Serum samples were collected and stored in the UVA COVID-19 biorepository. Anti-cardiolipin (aCL) and anti-b2glycoprotein1(ab2GLP1), IgM/IgG titres, were measured from stored samples, using the enzyme-linked immunosorbent assay (ELISA). Specimens were analysed at two distinct time-points/days during the patient's hospitalization for COVID-19. VTE incidence was collected retrospectively by chart review. The study was approved by the Institutional Review Board at UVA. Two-tailed Mann-Whitney two-sample rank-sum tests were conducted to examine whether there were significant differences in APS antibody levels, and mean change in APS levels between the two time points analysed, and VTE events. Additionally, logistic regression models were constructed to examine whether APS antibody levels and mean change in APS levels had a significant effect on the odds of observing a case of VTE. Results: There were 53 patients included in the study. The mean age of participants was 57.2 years (SD 13.9). VTE did not corelate with the levels of APS at studied time points, or the mean change in APS levels during the disease course. aCL IgM (p = 0.24), aCL IgG (p = 0.92), ab2GLP1 IgM (p = 0.79), and ab2GLP1 IgG (p = 0.79). Changes in the APS antibody levels during the course of the disease were not predictive of the odds of having VTE. Similarly, these changes did not predict the need for ICU care. Conclusions: This study shows that neither the presence of antiphospholipid antibodies nor the change in APS levels during the course of COVID-19 correlated with VTE events.
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Introduction: Microscopic polyangiits (MPA) is a rare ANCA-associated necrotizing vasculitis that affects the small vessels, often involving the lung or kidney. When presenting with diffuse alveolar hemorrhage, this disease warrants emergent treatment, often with plasma exchange. Here, we present a rare case of a patient presenting with alveolar hemorrhage in the setting of MPA and concurrent thrombotic thrombocytopenic purpura (TTP) with an extremely reduced ADAMTS13 activity. Case Report: A 77 y/o woman with HTN and PUD presented to outside facility with new onset anemia (Hb 6.3 g/dL). Positive Coombs test gave her a tentative diagnosis of hemolytic anemia, and she was transfused 2 U RBCs. Ten days later, she presented to our hospital with respiratory distress. Hb remained stable at 10.7 but had leukocytosis with WBC 22,000 with left shift, platelets 439. Vitals not consistent with sepsis though saturating 70-80% on room air. In the ED, she developed frank hemoptysis and was emergently intubated. CTA chest was negative for pulmonary embolus but demonstrated diffuse ground-glass opacities. COVID test negative. Bronchoscopy was consistent with diffuse alveolar hemorrhage (DAH), and she received tranexamic acid, crystalloids, 1 U RBCs. Suspicious for underlying vasculitic process, she was given pulse dose IV steroids (1 g methylprednisolone daily) and started plasma exchange. Creatinine on presentation was elevated at 1.77 but she continued to have adequate urine output and appropriate volume status. Her hospital course was marked by progressive thrombocytopenia with schistocytes appreciated on peripheral smear. ADAMTS13 activity <5% with inhibitor detected, consistent with TTP. Vasculitic workup revealed positive myeloperoxidase antibodies and p-ANCA consistent with MPA. Other rheumatologic workup ANA positive 1:640 and positive IgM cardiolipin antibodies;she had no personal autoimmune history but some family autoimmune disease including one daughter with systemic lupus erythematosus and another relative with Guillian-Barre. She remained intubated for 4 days and post-extubation experienced some short-lived ICU delirium but after made a remarkable recovery. She completed 12 total sessions of of plasma exchange and 3 of 4 planned doses of rituximab, to continue on oral steroids outpatient and prophylactic TMP-SMX. She was discharged to rehab facility on hospital day 20. Discussion: With diffuse alveolar hemorrhage on presentation, initial differential remained broad including delayed presentation of transfusion-related lung injury (TRALI) given recent history of transfusion. She had recently started hydralazine outpatient. Along with positive ANA, this could suggest drug-induced lupus. However, histone antibodies were negative, but results may have been compromised by steroids and plasma exchange. Both MPA and TTP can be deadly but are managed with similar treatment. Luckily, our patient was rapidly initiated on plasma exchange following hospitalization. Although further workup including ADAMTS13 and vasculitis labs were pending at the time, it is important to not delay treatment while awaiting results. Cased of concurrent TTP and ANCA-associated vasculitis have been described in the literature, but the full relationship between these two entities remains unclear. TTP may develop after starting glucocorticoids in the setting of ANCA vasculitis, so close monitoring is recommended. Disclosures: No relevant conflicts of interest to declare.