Antiphospholipid Antibodies Occurrence in Acute SARS-CoV-2 Infection without Overt Thrombosis.

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-ß2 glycoprotein I antibodies (aß2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aß2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases (p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer (p = 0.016), aPTT (p = 0.001), ferritin (p = 0.012), C-reactive protein (CRP) (p = 0.027), lymphocyte (p = 0.040), and platelet (p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Protein S Deficiency with Favourable Foetomaternal Outcome: A Case Report

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.

Acquired hemophilia A and deep vein thrombosis attributable to the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine-case report

Background: Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder that occurs in a sporadic, nonhereditary pattern. It is caused by circulating autoantibodies against clotting factor VIII that are triggered by several conditions. Moreover, AHA is clinically distinct from the inherited form of hemophilia A, with a different natural history and management approach, necessitating a high-index of suspicion in at-risk patients. Coronavirus disease 2019 (COVID-19) has emerged as a multisystemic disease whose manifestations are continuously being evaluated. There are few case reports of AHA associated with COVID-19 infection, while one case of AHA has been associated with COVID-19 vaccination. Similarly, deep venous thrombosis (DVT) frequently complicates COVID-19 infection, but two cases of DVT have been reported following COVID-19 vaccination. We report the occurrence of both AHA and DVT in a 63-year-old male patient within one week of receiving his first dose of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Case Description: Patient is a 63-year-old male who presented with a 3-day history of left lower extremity (LLE) swelling and pain. He was hemodynamically stable, but examination showed exquisite tenderness, ecchymosis, and pitting edema at the calf of the LLE. He had normal platelet counts at presentation but had mild anemia (11.9 g/dL) and elevated activated partial thromboplastin time (APTT) of 68.0 seconds. Venous Doppler ultrasound showed acute DVT in the left popliteal vein, necessitating commencement on heparin drip. He developed progressively worsening hematomas, symptomatic anemia that required red cell transfusions, and persistently elevated APTT despite stopping the heparin drip. Work up for pulmonary embolism, malignancy, and disseminated intravascular coagulopathy (DIC) were negative. Antiphospholipid antibodies and lupus anticoagulant were also negative. He had low factor VIII levels, tested positive for factor VIII inhibitor, and PTT mixing studies were consistent with acquired factor inhibitor. Treatment involved administration of Factor Eight Inhibitor Bypassing Activity (FEIBA) as well as intravenous methylprednisolone and cyclophosphamide. Following resolution of active bleeding with evidence of stable hemoglobin concentration, he was discharged home on oral prednisone and cyclophosphamide. Conclusion(s): This case report highlights the possibility of AHA and DVT as rare, potentially life-threatening adverse events that could occur following COVID-19 vaccination, which is currently the most effective tool employed in controlling the COVID-19 pandemic.Copyright © Annals of Blood. All rights reserved.

Autoimmune Diseases Affecting Hemostasis: A Narrative Review.

Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disorders associated with bleeding or thrombosis. In addition, there exist a vast array of autoimmune diseases that can also lead to either bleeding or thrombosis. For example, autoantibodies generated against clotting factors can lead to bleeding, of which acquired hemophilia A is the most common. As another example, autoimmune-mediated antibodies against phospholipids can generate a prothrombotic milieu in a condition known as antiphospholipid (antibody) syndrome (APS). Moreover, there exist various autoimmunity promoting environments that can lead to a variety of antibodies that affect hemostasis. Coronavirus disease 2019 (COVID-19) represents perhaps the contemporary example of such a state, with potential development of a kaleidoscope of such antibodies that primarily drive thrombosis, but may also lead to bleeding on rarer occasions. We provide here a narrative review to discuss the interaction between various autoimmune diseases and hemostasis.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) complicating myocarditis

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.

Lupus anticoagulants as a prospective independent predictor in COVID-19 patients.

OBJECTIVE: Lupus anticoagulant (LA) are commonly detected during SARS-CoV-2 infection. However, the relationship between LA and clinical significance is still unclear. METHODS: A retrospective chart analysis was performed on COVID-19 patients who were tested for LA at our hospital from March 2020 to November 2021. We analyzed the patient's characteristics based on the result of the LA test. In addition, subgroup analysis performed the LA-positive group who had undergone serial LA tests. RESULTS: A total of 219 COVID-19 patients were enrolled in the study, 148 patients (67.6%) were positive for LA test. The LA-positive group received more treatment of high flow nasal cannula (LA-positive 73.0%, LA-negative 57.7%, p = 0.024). The LA-positive group showed prolonged aPTT, higher levels of CRP and fibrinogen (all p's < 0.05). Among 148 LA-positive patients, 127 patients (86.5%) were found to be LA-positive within 10 days of SARS-CoV-2 positive, and LA-positive group confirmed a median time to LA loss of 10 days. However, there was a group that was negative for LA in the early stages of infection and became positive about 13 days later. A subgroup analysis showed that these patients had different characteristics due to their longer hospital stays and higher D-dimer levels. CONCLUSIONS: In COVID-19 patients, LA is expected to be associated to disease severity. Since the clinical significance of LA is different depending on the onset time of LA positivity, the LA test is suggested to be done at diagnosis of SARS-CoV-2 infection, even if LA is negative, follow-up test should be considered within 10 days.

COVID-19 and antiphospholipid antibodies.

Antiphospholipid syndrome and the coagulopathy of COVID-19 share many pathophysiologic features, including endotheliopathy, hypercoagulability, and activation of platelets, complement pathways, and neutrophil extracellular traps, all acting in concert via a model of immunothrombosis. Antiphospholipid antibody production in COVID-19 is common, with 50% of COVID-19 patients being positive for lupus anticoagulant in some studies, and with non-Sapporo criteria antiphospholipid antibodies being prevalent as well. The biological significance of antiphospholipid antibodies in COVID-19 is uncertain, as such antibodies are usually transient, and studies examining clinical outcomes in COVID-19 patients with and without antiphospholipid antibodies have yielded conflicting results. In this review, we explore the biology of antiphospholipid antibodies in COVID-19 and other infections and discuss mechanisms of thrombogenesis in antiphospholipid syndrome and parallels with COVID-19 coagulopathy. In addition, we review the existing literature on safety of COVID-19 vaccination in patients with antiphospholipid antibodies and antiphospholipid syndrome.

Anti-phospholipid antibodies were associated with clinical symptoms, disease severity and mortality among hospitalized COVID-19 patient

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.

Paediatric Aps - Children Are Not Just Small Adults

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.

Case report: Covid-19 and disseminated tuberculosis coinfection unveiling catastrophic antiphospholipid antibody syndrome: An association or de novo phenomenon

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).

All in the Marrow - a Case of Primary Bone Marrow Oedema

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.

Variability among commercial batches of normal pooled plasma in lupus anticoagulant testing.

INTRODUCTION: Lupus anticoagulant (LA) testing requires normal pooled plasma (NPP) in performing mixing studies and can be used for normalized ratios of clotting times (CTs). The aims were to demonstrate whether significant differences in clotting times between two batches of a same commercial NPP (CRYOcheck™) directly affect NPP-based cut-off values. METHODS: Diluted Russell Viper venom time (DRVVT) and activated partial thromboplastin time (aPTT) were used for LA testing. Screening, mixing and confirm tests were performed with Stago® instruments and reagents. Two batches of commercial NPP (A1291 and A1301 from CRYOcheck™; frozen) were compared in the determination of cut-off values. Cut-off values were defined as 99th percentile values of 60 healthy donors and compared with Mann-Whitney U test. RESULTS: Cut-off values obtained with the two NPP batches were significantly different for DRVVT (screen normalized ratio: 1.09 vs. 1.24, screen mix: 41.9 s vs. 38.9 s; index of circulating anticoagulant: 5.0 vs. 8.4; all had p-value <.001). On the contrary, no significant differences were observed for aPTT (screen normalized ratio: 1.32 vs. 1.34; p-value = .4068, screen mix: 37.8 s vs. 38.1 s; p-value = .1153) except for index of circulating anticoagulant: 9.6 versus 10.4 (p-value <.05). CONCLUSION: This study demonstrates that differences between two commercial NPP batches produced by a same manufacturer influenced LA cut-off values used for mixing studies and normalized ratios. Adequate cut-off setting, taking into account NPP CTs, is important to provide accurate conclusion about the presence or absence of a LA and avoid potential clinical impact.

Severe Thrombocytopenia, Thrombosis and Anti-PF4 Antibody after Pfizer-BioNTech COVID-19 mRNA Vaccine Booster-Is It Vaccine-Induced Immune Thrombotic Thrombocytopenia?

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a serious and life-threatening complication occurring after adenovirus-vector COVID-19 vaccines, and is rarely reported after other vaccine types. Herein, we report a case of possible VITT after the Pfizer-BioNTech mRNA vaccine booster, who presented with extensive lower limb deep vein thrombosis, severe thrombocytopenia, markedly elevated D-dimer and positive anti-PF4 antibody occurring 2 weeks post-vaccination, concurrent with a lupus anticoagulant. A complete recovery was made after intravenous immunoglobulin, prednisolone and anticoagulation with the oral direct Xa inhibitor rivaroxaban. The presenting features of VITT may overlap with those of antiphospholipid syndrome associated with anti-PF4 and immune thrombocytopenia. We discuss the diagnostic considerations in VITT and highlight the challenges of performing VITT confirmatory assays in non-specialized settings. The set of five diagnostic criteria for VITT is a useful tool for guiding initial management, but may potentially include patients without VITT. The bleeding risks of severe thrombocytopenia in the face of thrombosis, requiring anticoagulant therapy, present a clinical challenge, but early recognition and management can potentially lead to favorable outcomes.

CLOTTING AND COVID-19: IT IS NOT ALWAYS VTE

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

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

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

Association of Lupus Anticoagulant status with Disease Course in SARS-CoV-2 (COVID-19) Infection.

Background: We investigated the importance of lupus anticoagulant (LA) in patients with SARS-CoV-2. Methods: Medical records of 41 SARS-CoV-2 infected patients were reviewed. Patients were classified into two groups according to the frequency of positive LA test results: "LA (-)" and "LA (+) ≥1" (LA positive at least once). Statistical analysis was performed to determine the association between LA presence and change in LA test results and disease course according to both hospital days (HD) and days after diagnosis (DD). Results: The prevalence of LA was 51.2%. Averagely, the first change in LA test result occurred during DD 12-13 and between HD 9-10. The second change occurred on DD 15-16 and HD 13-14. The presence of LA was associated with severe disease (P = .004) but was not associated with thrombotic complications or mortality. The change of results from negative to positive or vice versa or the frequency of the changes was not associated with disease severity, thrombotic complications, or mortality. Conclusions: LA positivity can be regarded as one of the findings suggesting more serious SARS-CoV-2 infection.

Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units: A retrospective cohort study.

Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19. Patients/Methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents. Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein. Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.

Symptomatic Renal Infarct Secondary to COVID-19 Infection and Concomitantly Positive Antiphospholipid Antibody

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.

Scleroderma Renal Crisis and COVID—Is There an Association?

Scleroderma renal crisis (SRC) is a rare but potentially devastating complication of systemic sclerosis as it is associated with significant morbidity and mortality. We present an interesting case of a patient who developed SRC following infection with COVID-19. A 37-year-old female presented with new-onset hypertension, AKI, anemia and thrombocytopenia. She had a history of diffuse cutaneous systemic sclerosis diagnosed 8 years ago, that had been well controlled with immunosuppression. The patient had contracted COVID-19 infection about 2 weeks ago but had remained largely asymptomatic except for a sore throat. Urinalysis revealed sub-nephrotic proteinuria but was otherwise bland. Peripheral blood smear was notable for 12-15 schistocytes per HPF. ADAMTS13 and complement levels were normal. Serologies for ANA, ANCA, anti-Scl70, anti-Jo1, anti-Sm, lupus anticoagulant, anti-beta2-glycoprotein I, anti-RNA polymerase III, RF, cryoglobulin, RPR, hepatitis and HIV, all returned negative. Renal biopsy revealed an arterial predominant thrombotic microangiopathy (TMA) (Figure) consistent with a diagnosis of SRC. The patient was treated with anti-hypertensives including an ACE-inhibitor, but her AKI continued to worsen, ultimately leading to dialysis dependence. SRC classically develops in patients with early or progressive diffuse cutaneous disease or positivity for anti-RNA polymerase III antibodies. Our patient did not have any such risk factors and rather developed SRC following infection with COVID-19. COVID-19 has been reported to cause TMA by inducing immune dysregulation via an overactive complement system. It is plausible that infection with COVID-19 triggered an exaggerated immune response, in turn leading to the development of SRC in our patient. COVID-19 may trigger SRC in patients with systemic sclerosis in the absence of other risk factors. (Figure Presented)

IT'S ALWAYS COCAINE: A RARE CASE OF LEVAMISOLEINDUCED COCAINE ASSOCIATED VASCULITIS WITH PULMONARY AND RENAL INVOLVEMENT

CASE: 58 year old woman presents with 1 month of dyspnea and productive cough. She also reported loss of smell and hematuria for 1 week. History was notable for hypertension, COPD, substance abuse, specifically crack cocaine, and unstable housing. On admission she was tachypneic and hypoxic, requiring supplemental O2. Exam revealed bilateral crackles, elevated JVP, and mild lower extremity edema, but no skin changes or rashes. Laboratory studies showed an elevated creatine of 7.9. CT chest imaging showed extensive bilateral ground glass opacities with increased septal lines. Infectious work-up, including SARSCoV-2 PCR, was negative. Dialysis was initiated for new renal failure. To determine the etiology of the renal failure, autoimmune studies were obtained and showed a positive ANA and p-ANCA (1:640) and a negative MPO and PR3. Kidney biopsy was consistent with levamisole-induced vasculitis (LIV) from cocaine use. Treatment with steroids was initiated. She was discharged on steroid therapy and outpatient hemodialysis. She had repeated admissions for volume overload due to missed dialysis, and she developed heart failure within the year. She was unable to make appointments to start outpatient rituximab therapy. IMPACT/DISCUSSION: Levamisole-induced vasculitis (LIV) is a complication of use of cocaine adulterated with levamisole. Levamisole is an antihelminthic medication with well known immunomodulatory effects. Increasingly used as a cocaine adulterant, it is believed to be a component of over 80% of cocaine samples in the US. Its use is thought to be driven by levamisole's synergistic effect on the dopaminergic effects of cocaine. Levamisole-induced vasculitis is a p-ANCA associated vasculitis associated with long-term use of cocaine mixed with levamisole. It has been reported with both inhaled cocaine and smoking crack cocaine. Levamisole is thought to induce production of autoantibodies including p-ANCA, ANA, and lupus anticoagulant leading to immune complex deposition and secondary hypercoagulability. The most commonly reported presentation is cutaneous purpuric lesions, most notably the ear, tip of the nose, and malar eminence. LIV can occur without skin involvement and renal and pulmonary involvement including nephritis, renal failure, and hypersensitivity pneumonitis, has been reported. LIV with significant organ involvement is often treated with steroids. Additional immunosuppressive therapies including rituximab, cyclophosphamide, and plasmapheresis have been reported in severe cases. CONCLUSION: This case illustrates a rare presentation of LIV marked by with renal failure and absence of skin lesions. While the health effects of cocaine are well known, the adverse effects of agents used to cut cocaine are less readily considered. LIV should be considered in a patient with substance use disorder presenting with new vasculitis. As this case illustrates, factors like unstable housing and ongoing substance use disorder can complicate management.