Sarcoidosis-Associated Immune Thrombocytopenic Purpura and Focal Segmental Glomerulosclerosis

Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.

Antiphospholipid antibody profile in a group of Algerian Covid-19 patients

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.

Dynamic and spatial transcriptional responses in COVID-19-related chilblains

"COVID-toes" are chilblains that occurred in patients who may have been exposed to SARS-CoV-2, but without COVID-19 symptoms and/or with negative PCR or serology. The literature suggests that chilblains are an unexpected consequence of a strong interferon-mediated antiviral response, but the underlying molecular mechanisms remain poorly understood. We thus sought to explore the physiopathology of COVID-related chilblains by using spatially and temporally resolved transcriptomics. We included 19 patients with COVID-toes, and performed a complete virological assessment to exclude SARS-CoV-2 infection including skin viral metagenomics. Some patients had clinical symptoms evoking viral infection, but none had COVID-19. Apart from low levels of non-conventional antiphospholipid antibodies, biological tests were unremarkable. We performed spatially resolved transcriptomics (Visium, 10X Genomics) in 3 patients at different timepoints and compared them with 1 vaccination-related chilblain. We observed a different transcriptional profile in COVID-toes compared with COVID-19 vaccine-related chilblains. IRF1, CXCL10, ISG15 and STAT1 were highly expressed in COVID-toes and their expression decreased over time, confirming an activation of interferon and JAK/STAT pathways that was absent in vaccine-related chilblains. The proportion of inflammatory cell types obtained by spatial deconvolution varied over time in COVID-toes. Migratory dendritic cells were present at early stages, while T lymphocytes populations increased later. Overall, this work explores the mechanisms of COVID-19-related chilblains using spatially and temporally resolved transcriptomics.Copyright © 2023

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.

First reported case of parvovirus triggering painful widespread livedoid vasculopathy: another virus causing hypercoagulability?

Livedoid vasculopathy (LV) is a noninflammatory thrombotic disease caused by occlusion of dermal small vessels associated with systemic autoimmune disorders and coagulopathies. However, LV is often reported as being 'idiopathic', despite extensive investigation. We report a case of severe LV in an otherwise healthy 27-year-old woman, associated with parvovirus infection. The patient presented with a short history of a livedoid rash initially covering her torso, which spread to acral sites. Burning pains in the lower limb caused reduced mobility;systemically, she remained well and stable throughout. Examination revealed generalized acral skin pallor, livedoid patches of violet erythema and purpura with deep serpiginous ulcerations over extensor aspects of upper and lower limbs with a more broken/racemosa nonulcerated livedoid appearance on the trunk. On admission a transaminitisareas continued to ulcerate. Codeine was present with a creatine kinase of 1569 U L.1, but other blood test results were unremarkable including erythrocyte sedimentation rate, complement, cryoglobulins, antinuclear antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigen, rheumatoid factor, myositis screen, antiphospholipid screen and thrombophilia screen. Parvovirus IgG and IgM were both positive and tested for, as the patient's young daughter had recently been diagnosed with 'slapped cheek disease'. Magnetic resonance imaging of the thighs showed a diffuse mild myositis;electromyography, nerve-conduction studies, barium swallow and computed tomography of the chest, abdomen and pelvis were all normal. An incisional skin biopsy was performed, which revealed a blood vessel with organizing (Solimani F, Mansour Y, Didona D et al. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2. J Eur Acad Dermatol Venereol 2021;35: e649- 51) have been reported. The main proposed mechanisms for AstraZeneca vaccine-induced pemphigus could be a hyperimmune reaction in genetically predisposed individuals, with eventual formation of anti-desmoglein antibodies. An alternative hypothesis is that vaccine components could act as foreign antigens resulting in a cross-reaction with pemphigus antigens. The close association of COVID-19 vaccination with the acute onset of pemphigus in our patient, as well as exacerbations after subsequent vaccine administration, is more than coincidental. Considering the recent pandemic with COVID-19 and the widespread administration of the COVID-19 vaccine, continued observation and documentation of true adverse events is essential.

A Persistent Nightmare: A Case of Recurrent Brachial Artery Thrombosis

Background Brachial artery thrombosis can be seen with thromboembolism, hypercoagulability, and arterial thoracic outlet syndrome. Case A 33-year-old healthy female construction worker presented with right hand discoloration and pain. She suffered a COVID-19 infection 8 weeks prior with hand symptoms developing shortly thereafter. She could no longer work due to the pain. Duplex ultrasound and CTA of the right upper extremity (Figure) demonstrated localized thrombosis of the right brachial artery. The workup yielded no aortic or intracardiac thrombus, and cardiac event monitor showed no atrial arrhythmia. She underwent thrombectomy with brachial artery stenting and was found, during surgery, to have distal ulnar artery occlusion. Two days post-op, she had recurrent pain and was found to have brachial artery recurrent thrombosis. She underwent urgent brachial-brachial bypass. Arm pain continued despite graft patency, so ulnarpalmar bypass was performed. Decision-making Hypercoagulability workup, including antiphospholipid antibody, protein C, protein S, homocysteine, and Lp(a), was negative. Neither central thrombus on TEE nor evidence of thoracic outlet syndrome was found. As a diagnosis of exclusion, brachial artery thrombosis was ascribed to COVID infection. Despite rivaroxaban, the patient developed gangrene (Panel C) requiring partial digit amputation. Conclusion We present a case of COVID-19-induced recurrent brachial artery thrombosis despite surgical intervention. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

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.

Catastrophic Antiphospholipid Crisis Triggered by Anticoagulant Switch

Case report - Introduction: The COVID-19 pandemic led to drastic changes for some patients on warfarin for venous thromboembolic (VTE) disease and atrial fibrillation. Warfarin monitoring necessitates frequent interaction with healthcare workers, which is sufficiently risky for COVID-19 transmission. As a result, selected patients were swapped over to novel oral anticoagulants (NOACs). Our patient was changed without investigating for antiphospholipid syndrome (APLS);it later transpired he was triple antibody positive. He presented in a crisis and we describe his narrative. Patients on warfarin due to presumed unprovoked venous thromboembolic disease should not be swapped to NOACs without completing, or checking, previous antiphospholipid antibody testing. Case report - Case description: A 73-year-old gentleman presented locally in August 2020 with erythema over the anterolateral surface of his left leg. He was initially treated with antibiotics for presumed cellulitis. Within a few days this lesion became necrotic and rapidly spread. At this point, he was transferred to a tertiary rheumatology centre. Within days to weeks, he developed several necrotic lesions affecting his trunk and limbs, with facial sparing noted. Approximately 30-35% of his whole-body surface became involved. He soon developed an oxygen requirement, with CTPA demonstrating lymphocytic interstitial pneumonitis without evidence of pulmonary emboli (PE). Throughout his admission, he had several other pathologies such as hyponatraemia that required level 2 care and severe noninfectious diarrhoea. Skin biopsy identified thrombotic vasculopathy. Serology confirmed triple positive antiphospholipid antibody status and a dsDNA titre of>400 iU/mL. This was the first-time serology had been undertaken despite a history of three deep vein thrombosis (DVT) episodes and two PE incidents. He had no history of SLE symptoms. His initial management for vasculitis secondary to APLS at the point of limited necrosis consisted of IV methylprednisolone followed by rituximab and PO prednisolone. While there was some delay in the progression of his disease, new areas of necrosis arose, leading to the patient receiving cyclophosphamide. Low molecular weight heparin was used for anticoagulation. This gentleman later developed proteinuria and neurological symptoms, fulfilling the criteria for catastrophic antiphospholipid syndrome. He received plasma exchange, without an improvement. He developed complications from his disease and treatment, including poor wound healing. It became apparent his condition would not improve and active treatments were stopped. He passed away 6 weeks after initial presentation. Prior to his admission to hospital, his warfarin was swapped to a NOAC. This is thought to have been the trigger behind catastrophic thrombosis. Case report - Discussion: After excluding other conditions such as necrotising fasciitis, this gentleman was rapidly started on IV methylprednisolone to halt any further progression. This is because glucocorticoids have the greatest evidence base for managing this poorly understood acute disease manifestation. After this failed to manage his condition, he was given a further immunosuppressive agent in the form of rituximab. This was used after his serology confirmed triple antibody status. It was hoped this would stop any further immunological mediated disease progression. Oral prednisolone was started at 40mg at this stage and kept under review with a tapering schedule. Cyclophosphamide was given within a few days of rituximab, with hope of a quicker onset of action. A careful MDT decision was made on these drug choices, particularly regarding their combined use and appreciating their side effect profiles. Cyclophosphamide has evidence behind its use, especially for those with APLS associated with lupus. While he did not develop any infections related to treatment, his condition progressed. Case reports suggest that plasma exchange can be useful in the management of catastrophic antiphospholipid syndrome, so the team recommen ed this. Consent at this stage became tricky due to his altered mental status, but it was felt he did demonstrate capacity for this specific decision. As his condition did not improve after this level of immunosuppression, the team reached the decision that no other treatments would likely change the outcome. He remained on oral steroids for the remainder of his admission. The other management facet of APLS crises pertains to anticoagulation. Low molecular weight heparin was recommended by the haematologists. His NOAC was stopped after the diagnosis was confirmed. Warfarin was restarted later in his admission given he had been well on this for years. Case report - Key learning points: This fascinating case exemplifies the importance of completing an antiphospholipid antibody screen for patients who present with unprovoked venous thromboembolic disease. NOACs are commonly used anticoagulant medications. Several case reports have demonstrated that patients with antiphospholipid syndrome experience breakthrough thromboembolic events when treated with NOACs. The highest risk is associated with history of arterial thrombosis and those with triple positive antibody status. Three clinical trials have either been completed or are in the process of investigating whether NOACs sufficiently prevent thromboembolic disease in these patients. The TRAPS study compared rivaroxaban to warfarin in those with triple antibody positive antiphospholipid syndrome. The study was terminated early given that higher adverse events were observed in the rivaroxaban arm (19%, n11/59) versus warfarinised patients (3%, n2/61). The RAPS study found no difference in thromboembolic risk and results from the ASTRO-APS study looking into apixaban are awaited. There is insufficient evidence to suggest that NOACs prevent VTE in a similar fashion to warfarin, so many still advocate the use of warfarin. The optimal immune management of this acute complication is not well elucidated, with a shortfall in mechanistic pathological understanding. The conference will generate discussion on this subject matter in detail. During the COVID-19 pandemic, it has been observed for patients to change anticoagulation from warfarin to NOACs. Given NOACs do not require monitoring, this medication change reduces the number of interactions patients have with healthcare services. We postulate this change triggered the crisis in our patient, where we suggest continuation of warfarin would have been ideal. This is due to the history of several unprovoked thromboembolic events without a prior antiphospholipid screen being completed. Dissemination of learning points from this case are imperative to ensure decision-making encompasses patients who may have undiagnosed antiphospholipid syndrome.

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).

A Series of Catastrophic Events

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

A RARE PRESENTATION OF COVID-19-ASSOCIATED CENTRAL VENOUS THROMBOSIS

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Due to a wide range of clinical presentations, central venous thrombosis (CVT) is a rare neurologic condition that can be difficult to diagnose. Since the COVID-19 pandemic, more cases of venous thromboembolic events have emerged and been found associated with COVID-19. We detail a potential case of COVID-19 associated CVT. CASE PRESENTATION: A 28-year-old female with past medical history of obesity, polycystic ovary syndrome, recurrent sinusitis, and presumed history of COVID-19 infection with anosmia, ageusia, and sinusitis symptoms three- months prior presented to the hospital with 1-month history of worsening, right-sided pain behind her ear, eye, head, posterior neck and shoulder, nausea, and photophobia, which had worsened in the last 5 days. She initially tried over-the-counter medications with no improvement. Vital signs were unremarkable. Examination was notable for frontal sinus and right postauricular tenderness to palpation. C- reactive protein was elevated at 26.2 mg/L. Non- contrasted brain computed tomography (CT) was concerning for right transverse sinus and superior sagittal sinus thrombosis. Brain magnetic resonance imaging (MRI) showed early signs of cortical edema and venous infarction and findings concerning for right mastoiditis. Intracranial venous MRI showed complete thrombosis of the right transverse and sigmoid sinus, superior sagittal sinus, and most of the superior draining cortical veins. Heparin drip was started. Initial empiric antibiotics for mastoiditis were stopped. Hyper-coagulopathy work-up with beta- 2 glycoprotein 1 antibodies and phospholipid antibodies were negative. As there were no other inciting factors for CVT found and no history of positive COVID-19 test, a COVID-19 antibody immunoassay was obtained and returned positive. The patient did not have a history of COVID vaccination. She was discharged on warfarin and enoxaparin. Anticoagulation was stopped after 6 months with repeat imaging showing resolution of clot burden. DISCUSSION: Usual risk factors associated with CVT are morbid obesity, hormone replacement therapy, oral contraceptive use, hereditary thrombophilia, and pregnancy. Literature on CVT related to COVID-19 is limited. In 41 documented cases, the average age of incidence is 50 years old and median onset of neurological symptoms from initial COVID-19 diagnosis is 7 days [0 to 21 days]. Our patient's neurological symptoms began about 3 months after her initial diagnosis, potentially making it the first known case of COVID-19 associated CVT with symptom onset past 21 days. Anticoagulation is the mainstay treatment for CVT, and duration depends on the presence of provoking factor. CONCLUSIONS: In patients with new neurologic symptoms and recent diagnosis of COVID-19, CVT should be considered in the differential diagnosis as it can initially present in a subtle manner. Early recognition could improve patient morbidity and mortality. Reference #1: Abdalkader, M., Shaikh, S. P., Siegler, J. E., Cervantes-Arslanian, A. M., Tiu, C., Radu, R. A., Tiu, V. E., Jillella, D. v., Mansour, O. Y., Vera, V., Chamorro, Á., Blasco, J., López, A., Farooqui, M., Thau, L., Smith, A., Gutierrez, S. O., Nguyen, T. N., Jovin, T. G. (2021). Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. Journal of Stroke and Cerebrovascular Diseases. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105733 Reference #2: Idiculla, P. S., Gurala, D., Palanisamy, M., Vijayakumar, R., Dhandapani, S., Nagarajan, E. (2020). Cerebral Venous Thrombosis: A Comprehensive Review. European Neurology (Vol. 83, Issue 4). https://doi.org/10.1159/000509802 Reference #3: Ostovan VR, Foroughi R, Rostami M, et al. Cerebral venous sinus thrombosis associated with COVID-19: a case series and literature review. Journal of Neurology. 2021 Oct;268(10):3549-3560. DOI: 10.1007/s00415-021-10450-8. PMID: 33616740;PMCID: PMC7897893. DI CLOSURES: No relevant relationships by Shu Xian Lee No relevant relationships by Arif Sarwari No relevant relationships by Benita Wu

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

HIGH PREVALENCE of SERUM AUTOANTIBODIES in SEVERELY ILL COVID-19 PATIENTS HOSPITALIZED in the INTENSIVE CARE UNIT

Background: Coronavirus Disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a wide range of clinical manifestations 1. Although COVID-19 was initially considered a respiratory infection, it was shortly recognized as a multisystemic disorder associated with heightened infammatory responses, including autoimmune phenomena 1. The presence of autoantibodies (AAbs) has been described in COVID-19 patients, highlighting the state of immune dysregulation in COVID-19 1. The clinical signifcance of AAbs, however, is still elusive. Objectives: To assess the prevalence of AAbs in critically ill, mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU) and investigate whether AAbs influence the clinical outcome of these patients. Methods: The current study evaluated prospectively from March 8th, 2021 to May 10th, 2021 the presence of AAbs against nuclear antigens (ANA), extracta-ble nuclear antigens (ENA), neutrophil cytoplasmic antigens (ANCA), cyclic cit-rullinated peptides (anti-CCP), double stranded-DNA (anti-dsDNA), cardiolipin (anti-CL), β2-glycoprotein-I (anti-β2-GPI), thyroid peroxidase (anti-TPO), and thyroglobulin (anti-TG) in critically ill COVID-19 patients upon admission in the ICU (n=217). Samples from 60 COVID-19 patients that were available 15 days after ICU admission were further analyzed for the evaluation of de novo AAbs production. Serum samples of age and sex matched healthy individuals before the COVID-19 pandemic were used as a control group (n=117). Results: COVID-19 patients treated in ICU had more commonly at least one AAb compared to age and sex matched controls (174/217, 80.2% vs 73/217, 62,4%, p< 0,001). More specifcally, COVID-19 patients expressed more frequently ANAs (48.4% vs 21.4%, p<0.001), anti-dsDNA (5.1% vs 0%, p=0.01), anti-CCP (8.3% vs 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs 9.4%, p=0.005) than controls. The majority of critical COVID-19 patients who were positive for AAbs (144, 82.8%) expressed reactivity in up to three autoantigens with the most prominent being ANA, anti-phospholipid, ANCA and anti-TPO AAbs. AAbs-positive patients demonstrated more robust anti-SARS-CoV-2 humoral responses compared to AAbs-negative patients [detectable anti-SARS-CoV-2 S1-protein IgG antibodies: 150 (86.2%) vs 28 (65.1%), p=0.001;adequate neutralizing activity: 159 (91.4%) vs. 33 (76.7%), p=0.007]. The two groups, however, did not differ in terms of clinicoepidemiologic characteristics or the incidence of death in the ICU. Convalescent COVID-19 patients (n=111) compared to those who died (n=106), did not differ in the prevalence of serum AAbs or antibody responses against SARS-CoV-2. Differences were only shown in clinicolaboratory parameters including patients' age, comorbidities, O2 saturation, infammatory markers, and in-hospi-tal prognostic scores as expected. Paired samples testing (n=60) revealed that 45 patients had at least one newly induced AAb, 28 patients lost at least one reactivity and only 6 patients didn't show any seroconversion. The most common new-onset AAb reactivity was against anti-CL (IgG isotype) (n=21) followed by ANA (n=20), anti-β2-GPI (IgG isotype) (n=11), myositis-related antigens (n=13) and ENAs (n=9);nevertheless, no associations with clinicoepidemiologic features or COVID-19 outcome were revealed. Conclusion: Patients with severe COVID-19 express AAbs more commonly than age and sex matched controls, suggesting that SARS-COV-2 infection may induce a hitherto unknown B-cell autoreactivity. The presence of autoantibodies does not play a role in the outcome of SARS-COV-2 infection. However, further studies are needed to defne their role in future development of systemic autoimmune disorders or the long-COVID syndrome.

SARS-COV-2 INFECTION CAUSED THROMBOSIS in the LUPUS MODEL with ANTIPHOSPHOLIPID ANTIBODY, whereas COVID-19 ASSOCIATED THROMBOSIS WAS IRRELEVANT in PATIENTS with POSITIVE ANTIPHOSPHOLIPID ANTIBODY

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.

AN UNUSUAL ASSOCIATION between THROMBOTIC THROMBOCYTOPENIC PURPURA and PRIMARY ANTIPHOSPHOLIPID SYNDROME

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangio-pathic haemolytic anemia, consumption thrombocytopenia and organ injury, particularly kidney failure and neurological manifestation1. Two forms are distinguished: the hereditary one, caused by a deficit of the metallopro-tease ADAMTS13, and the idiopathic one characterized by the presence of antibodies directed against ADAMTS13. The second one is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, disseminated malignancies and drugs. Antiphospholipid syndrome (APS) is a clinical immunological condition characterized by thromboembolic events, repe-tead miscarriages or stillbirth and thrombocytopenia;it can be a primary disorder or due to connective tissue disease, in particular systemic lupus erythematosus2. Objectives: We describe a case of TTP associated with a primary APS. The real clinical challenge lies in the differential diagnosis between TTP and anti-phos-pholipid antibody syndrome. Methods: A 37-year-old man presented to the emergency department for short-term episodes of anesthesia of the right upper limb and face with spontaneous resolution. In his past medical history, he suffered of antiphospholipid syndrome treated with warfarin. Upon admission, blood tests revealed severe thrombocytopenia, haemolytic anemia with schistocytes on peripheral blood smear, low thrombin time and prolongation in the prothrombin time. Neurological symptoms were assessed by electroencephalogram and CT brain, resulted negative, while a brain MRI revealed acute-subacute ischemic stroke. Based on these fndings we suspected a diagnosis of TTP, subsequently confrmed by reduced activity of ADAMTS-13 with borderline ADAMTS-13 inhibitory antibodies. Immunological testing confrmed positivity of antiphospholipid antibodies and antinuclear antibodies. Results: According to the last guidelines3 about management of acute episode of TTP, immediate therapy with high-dose corticosteroids (prednisone 1 mg/kg) and plasmapheresis was started and then we added infusion of ritux-imab (375 mg/m2/week for 4 times). Efficacy of treatment was evaluated by weekly dosage of ADAMTS13 activity, with a gradual rise in values (3 → 78%) and improvement in symptoms and laboratory examination. After persistent remission, we gradually reduced steroid therapy. Few months later, in February 2021, patient developed a bilateral comunitary pneumonia, that required hospitalization, oxygen-therapy (also with C-PAP) and endovenous antibiotics. After two weeks patient was discharged from hospital in good clinical health and he was subjected to periodic outpatients visits. Disease activity was in remission, so steroid therapy was reduced and recently we added hydroxychloroquine for APS. Some days ago patient developed covid-19 infection, despite vaccination, and he was treated with monoclonal antibodies, with good clinical response. Conclusion: We have described a rare clinical case of TTP, despite concomitant warfarin treatment for primary anti-phospholipid syndrome. A careful follow-up of these medical conditions is recommended for patient's fragility and for the risk of related serious clinical complications.

EVALUATION of the POTENTIAL INDUCTION of AUTOANTIBODIES after the ANTI-SARS-COV2-VACCINATION in A COHORT of PATIENTS with TRIPLE POSITIVITY for ANTIPHOSPHOLIPID ANTIBODIES

Background: Anti-SARS-CoV2 vaccines showed a good efficacy in prevention of severe COVID-191. Their potential in induction of autoantibodies (abs) has not been well established1. One recent study demonstrated an increase of abs' titre after anti-SARS-CoV2 vaccination only in patients with already pre-existing positivity2. Objectives: To evaluate the potential induction of abs after anti-SARS-CoV2 vaccination in a triple positive antiphospholipid antibodies (aPL) cohort. Methods: 18 subjects were enrolled [M/F= 17/1;median age=52 years;5 Primary Antiphospholipid Syndrome (PAPS), 5 Systemic Lupus Erythematosus (SLE) with associated APS and 8 aPL carriers (1 Behçet Disease, 1 SLE, 4 Undifferentiated Connective Tissue Disease, 2 with no diagnosis of systemic autoimmune disease)]. Serum samples were collected before the first (T0) and at least one month after the second administration (T1) of the anti-SARS-CoV2 vaccine (16 BNT162b2, 1 mRNA-1273, 1 Gam-COVID-Vac). A wide panel of abs were evaluated through routinely methods. Results: None developed any additional sign of autoimmune diseases upon vaccination. Patients majority did not display any new autoantibody posi-tivity (Table 1). Changes were observed in 3 patients: 1) one aPL carrier patient who was antinuclear antibodies (ANA) negative at T0 was found to be ANA positive at T1 [negative anti-double stranded DNA and anti-extractable nuclear antigen (ENA)];this patient was actually ANA positive in her clinical history;2) one aPL carrier patient affected by SLE, who was IgM and IgG aCL and IgG aB2GPI positive at T0, turned positive for IgM and IgA aB2GPI;3) one aPL carrier patient affected by Behçet Disease, who was positive for IgM aCL and for IgM aB2GPI at T0, turned positive for IgA aCL and IgA aB2GPI. All emerging aPL were low titre. None of the patients displayed raising aPL titres from low to medium-high. Conclusion: Anti-SARS-CoV2 vaccination did not induce any clinical signs of autoimmunity in a cohort of patients with triple aPL positivity. Serology for autoantibodies remained stable in the majority of patients. Few patients experienced the emergence of low titre aPL, possibly as an expected inter-assay variation rather than an evolving 'serological fare'.

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.

NON-UREMIC CALCIPHYLAXIS SECONDARY TO ACUTE COVID-19

CASE: A 40-year-old white female with medical history significant for COVID-19 infection three months prior to presentation and previous spontaneous miscarriage presented with bilateral lower extremity lesions present for several weeks and described as “sunburn-like” with blistering. The lesions were initially located on her anterior thighs and spread to the lateral thighs and lower back. On presentation, she was found to have several distinct lower extremity lesions, with evidence of necrosis and eschar formation, along with blackened mottled skin. The lesions were extremely painful to the patient. Laboratory evaluation demonstrated hyponatremia, elevated ESR and CRP, with normal serum creatine and calcium. Calciphylaxis was confirmed with biopsy. The patient was treated with strict wound care to prevent infection and received sodium thiosulfate three times weekly and anticoagulation with apixaban due to concern for underlying hypercoagulability. An extensive work-up for underlying autoimmunity and hypercoagulability demonstrated presence of antiphospholipid antibodies with positive Cardiolipin IgM, lupus anticoagulant, and a homogenous ANA patern that showed a titer of 1:160. Her clinical status improved on extensive pain regimen and on follow-up one week later, the lesions were unchanged. IMPACT/DISCUSSION: Calciphylaxis is a known dermatologic finding that is typically diagnosed in the setting of End-stage Renal disease (ESRD). It presents with non-healing, painful skin ulcers that are at a high risk for infection and have poor healing. In the absence of ESRD, calciphylaxis is rare but has been reported in certain settings including hypercoagulable states and/ or autoimmune conditions. We present a case that has an absence of known etiologies for calciphylaxis and hypothesize that this is due to a hypercoagulable state caused by recent COVID-19 infection, or COVID-19 aggravating an underlying hypercoagulable state. This case offers an uncommon diagnosis with an even rarer presentation. Calciphylaxis must be confirmed with biopsy and is extremely debilitating and painful. In the setting of non-uremic calciphylaxis, prevention of infection and management of pain should be prioritized. Additionally, this case offers a platform to identifying COVID-19 as a risk factor for development of calciphylaxis in previously healthy individuals. CONCLUSION: The general internist should be aware of non-uremic calciphylaxis and also be concerned for hypercoagulable state induced from COVID-19. It is important to have accurate history-taking and consider delayed reactions, as in this case.