LUPUS ANTICOAGULANT HYPOPROTHROMBINEMIA SYNDROME: A CASE REPORT

Lupus anticoagulant hypoprothrombinemia síndrome (LAHPS) is a rare entity. A 54-year-old woman diagnosed with systemic lupus erythematosus (SLE) present in August 2020 with cerebellar haemorrhage, coagulation factor II deficiency was found. After increasing corticosteroid dose and adjustment of immunosuppressive therapy FII levels increased. She has no presented new haemorrhagic events.

Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.

Excessive Subchorionic Fibrinoid Deposition as a Component of Massive Perivillous Fibrin Deposition: A Case With Maternal Immune Thrombocytopenia

Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are overlapping placental disorders of unknown etiology, associated with adverse obstetric outcome, and a significant risk of recurrence. We describe a 31-year-old mother with asymptomatic thrombocytopenia throughout pregnancy and a positive lupus anticoagulant. She delivered a normal female neonate at term, whose weight was small for gestational age, with a placenta weighing less than the 10th percentile. Placental examination showed MPFD together with excessive subchorionic fibrinoid deposition. The placenta showed diffuse C4d deposition and an immune-mediated reaction was postulated for the pathogenesis of the placental changes. We suggest that excessive subchorionic fibrinoid deposition may be part of the morphologic spectrum of MFI/MPFD.

Antiphospholipid Syndrome Associated with Nonradiographic Axial Spondyloarthritis

Herein, we describe a patient with antiphospholipid syndrome (APS) associated with nonradiographic axial spondyloarthritis (NRAS). A 31-year-old woman with a past medical history of uveitis experienced a pulmonary thromboembolism in March 2014 and was treated with rivaroxaban (20 mg/day). Five months later, she started complaining of low back pain. The results on contrast-enhanced sacroiliac magnetic resonance imaging were normal. Laboratory tests revealed positive HLA-B27 and the presence of lupus anticoagulant and IgM anticardiolipin. The diagnoses of APS and NRAS were made. The patient was treated with rivaroxaban for APS and sulfasalazine (2 g/day), respectively. As she showed the presence of lupus anticoagulant antibodies in blood, she did not receive nonsteroidal anti-inflammatory drugs. After 6 months, the patient was asymptomatic, without lumbar pain; she also showed normalization of the erythrocyte sedimentation rate and the C-reactive protein and vitamin D levels, good control of lumbar pain, and no new uveitis episodes. The APS was also stable. To the best of our knowledge, this is the first reported case of NRAS associated with APS.

Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice

Objective Lupus anticoagulant (LAC) and antiphospholipid antibodies (aPL), both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic work-up for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study is to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice. Methods In this retrospective single center study indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018. Results During the study period, 16,847 single aPL tests were performed in 2,139 patients. In 212 patients ≥1 positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic work-up/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetrical complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of the antiphospholipid syndrome (APS), of whom 51% were newly diagnosed. Second positive aPL titers and titers of APS patients were significantly higher compared with positive aPL titers at first measurement (p < 0.05). Patients with indication arterial thrombosis and diagnostic work-up/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2GPI IgG compared with patients with other indications. Conclusion Prevalence of ≥ 1 positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.

Renal Function and Risk of Arterial Thrombotic Events in Patients Positive for Lupus Anticoagulant

Background: Patients with lupus anticoagulant (LA) are at risk for arterial and venous thromboembolic events. Recent work suggests that LA positive patients who experience thrombotic events in different vascular beds constitute distinct subgroups. To risk stratify patients, further work is needed to better characterize predictors for thromboembolic events in these subgroups. Aims: The aim of this study was to identify baseline characteristics and laboratory parameters associated with the development of arterial or venous thrombotic events. Methods: Patients with at least 2 previous positive LA tests were serially monitored for thrombotic events within the prospective Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Patients without clinical follow-up were excluded from this analysis. Statistical analysis was performed with RStudio (Version 1.1.442). Results: One-hundred-eighty-seven patients were followed (Table 1) for a median of 11.4 years and 1865 follow-up visits (median visit/patient=9). Fifty-seven prospective thrombotic events (TE), including 27 arterial thrombotic events (ATE) and 30 venous thrombotic events (VTE), were observed. This corresponded to 10-year prospective ATE, VTE and overall thrombosis incidences of 13.9% [95%CI: 8.3, 19.6], 18.8% [12.2, 25.4], and 32.0% [24.1, 39.8], respectively. (Figure 1). Thirty-seven of the 57 events occurred in patients with a prior history of thrombosis ("recurrent thrombosis"). In univariable competing risk analysis, age (subdistribution hazard ratio (SHR) = 1.02, 95% CI: 1.00-1.05, p=0.019), body mass index (BMI, 1.05, 1.00-1.11, p=0.042), history of ATE (3.14, 1.45-6.81, p=0.0038), active smoking (2.16, 1.00-4.62, p=0.049), diabetes (4.16, 1.47-11.8, p=0.0073), VKA use at baseline (0.42, 0.18-0.97, p=0.042), aCL IgM positivity (2.48, 1.05-5.83, p=0.038), aβ 2GPI IgM positivity (2.86, 1.18-6.93, p=0.020), mean platelet volume (1.17, 1.06- 1.30, p=0.0024), creatinine (3.76, 1.32- 10.7, p=0.013), and estimate glomerular filtration rate (eGFR, 0.98, 0.96-0.99, p=0.0011) were associated with prospective risk of ATE (Table 2). Conversely, the prospective risk of VTE was univariably associated only with prior history of VTE (3.26, 1.40-7.68, p=0.0061). After adjusting for traditional arterial thrombotic risk factors (age, sex, BMI, active smoking, diabetes,), history of ATE (SHR = 3.97, 95% CI: 1.71-9.025, p=0.0014), prior history of both ATE and VTE (3.87, 1.06-14.16, p=0.041), creatinine (3.93, 1.22-12.66, p=0.022), and eGFR (CKD-EPI, 0.96, 0.96-0.99, p=0.0037) remained independently associated with prospective risk of ATE (Table 2). In detail, the 10-year cumulative risk of ATE was 24.9% [95%CI: 8.8, 41.0], 15.0% [5.8, 24.2], and 6.7% [2.2, 13.8] in patients with a baseline eGFR less than 60 mL/min/1.73m 2, between 60 and 89 mL/min/1.73m 2, and greater than or equal to 90 mL/min/1.73m 2, respectively (Gray's test, p=0.019, Figure 2). Conclusion: Approximately 14% of patients persistently positive for LA experienced an ATE over 10 years. After adjusting for traditional arterial risk factors, decreased renal function was associated with an increased prospective risk of ATE. Notably, decreased renal function was not associated with development of VTE and the association with ATE was also independent of underlying SLE, LLD, or rheumatic disease (data not shown). Clinically, LA positive patients with decreased renal function may represent a subgroup that might benefit from more aggressive anti-thrombotic therapy or anti-thrombotic prophylaxis. Figure 1 Figure 1. Disclosures Pabinger: Bayer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.