Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion.

OBJECTIVE: The withdrawal of oral anticoagulation (OAC) in patients with SLE and secondary aPL syndrome (SAPS) who become seronegative has not been clearly investigated to date. Our aim was to evaluate the prevalence of aPL seroconversion and the prognosis of SLE patients with SAPS who withdrew OAC after aPL negativization. METHODS: We retrospectively analysed data of all SLE patients (ACR criteria) with SAPS (Sydney criteria) prospectively followed-up in our clinic. aPL seroconversion was defined as negativization of lupus anticoagulant, aCL, and anti-ß2glycoprotein-1 antibodies on two or more consecutive measurements, at least 12 weeks apart. OAC discontinuation was defined as the definitive withdrawal of all anticoagulants. RESULTS: Fifty-five out of 513 (10.7%) SLE patients had vascular SAPS. Sixteen patients (29.1%) became aPL seronegative during follow-up. Immunosuppressive therapy predicted aPL negativization (odds ratio 5.211, 95%CI 1.341, 20.243), whereas APS diagnosis prior to that of SLE (odds ratio 0.078, 95%CI 0.008, 0.799) and triple-positive profile (odds ratio 0.264, 95%CI 0.115, 0.609) were negative predictors of aPL negativization. OAC was discontinued in 13/55 patients (23.6%), after a median follow-up of 45 months (range 1-276) from aPL seroconversion. SLE-related modifiable risk factors for thrombosis were observed in 10/13 patients (77%) at the time of the thrombotic event. No thrombotic recurrences were observed during a mean follow-up time of 44 (19) months from OAC discontinuation. CONCLUSIONS: Our results suggest that OAC can be safely discontinued in SLE patients who became persistently seronegative for aPL, at least when aPL-related thrombotic events occurred in presence of other thrombotic risk factors.

Antiphospholipid antibodies and cerebrovascular thrombosis in the pediatric population: Few answers to many questions.

Most of the knowledge in pediatric antiphospholipid syndrome (APS) is derived from studies performed on the adult population. As in adults, antiphospholipid antibodies (aPL) can contribute to thrombosis, especially cerebrovascular thrombosis, in neonates and children. Since aPL have the potential to cross the placental barrier, and since the pediatric population is prone to infections, re-testing for their positivity is essential to specify their role in cerebrovascular thrombosis.In this review, we aimed at assessing the prevalence of aPL, criteria or non-criteria, in neonatal and childhood ischemic stroke and sinovenous thrombosis trying to find an association between aPL and cerebrovascular thrombosis in the neonatal and pediatric population. Also, we looked into the effect of aPL and anticoagulants/antiplatelets on the long term neurological outcomes of affected neonates or children. The questions regarding the prevalence of aPL among pediatric patients with cerebrovascular thrombosis, the relationship between the titers of aPL and incidence and recurrence of cerebrovascular events, the predictability of the long term neurological outcomes, and the most optimal anticoagulation plan are still to be answered. However, it is crucial for clinicians to screen neonates and children with cerebrovascular thrombosis for aPL and confirm their presence if positive.

Micronized / ultramicronized palmitoylethanolamide (PEA) as natural neuroprotector against COVID-19 inflammation.

Coronavirus Disease 2019 (COVID-19) is upsetting the world and innovative therapeutic solutions are needed in an attempt to counter this new pandemic. Great hope lies in vaccines, but drugs to cure the infected patient are just as necessary. In the most severe forms of the disease, a cytokine storm with neuroinflammation occurs, putting the patient's life at serious risk, with sometimes long-lasting sequelae. Palmitoylethanolamide (PEA) is known to possess anti-inflammatory and neuroprotective properties, which make it an ideal candidate to be assumed in the earliest stage of the disease. Here, we provide a mini-review on the topic, pointing out phospholipids consumption in COVID-19, the possible development of an antiphospholipid syndrome secondary to SARS-CoV-2 infection, and reporting our preliminary single-case experience concerning to a 45-year-old COVID-19 female patient recently treated with success by micronized / ultramicronized PEA.

Characteristics of Acquired Inhibitors to Factor VIII and Von Willebrand Factor Secondary to Systemic Lupus Erythematosus: Experiences From a Chinese Tertiary Medical Center.

OBJECTIVE: Because acquired hemophilia (AH) is a rare entity in systemic lupus erythematosus (SLE), we aimed to investigate the clinical features of SLE-related AH in Chinese patients. METHODS: This is a medical records review study carried out at a large tertiary care hospital in China from years 1986 to 2018. We searched the case database in Peking Union Medical College Hospital using the International Classification of Diseases. The clinical data on SLE-related AH patients were collected. RESULTS: A total of 9282 SLE patients had been hospitalized. Six female SLE-related AH patients were identified. Four patients had acquired hemophilia A (AHA), and 2 patients had acquired von Willebrand syndrome. Their mean age was 33.67 ± 13.77 years. Five patients had active disease. The mean SLE disease activity index measured at the time of diagnosis of AH was 10.50 ± 5.28. The average level of activated partial thromboplastin time was 86.5 seconds. Coexistence of secondary antiphospholipid syndrome and AHA was found in one case, and pulmonary embolism was observed 3 years later. After immunosuppressive therapy and symptomatic treatment, an overall remission rate of 83.3% was achieved. CONCLUSIONS: The frequency of SLE-related AH was low. The development of AH in SLE patients frequently occurs with active disease. The AH could be the first clinical presentation of SLE. Secondary antiphospholipid syndrome and AHA could appear in the same SLE patient. Early and aggressive treatment contributes to a favorable prognosis.

Nine-test panel has superior sensitivity to detect antiphospholipid antibody syndrome in patients with or without SLE.

Anti-phospholipid antibodies (aPL) and lupus anticoagulant (LAC) represent diagnostic criteria for systemic lupus erythematosus (SLE) and underlie anti-phospholipid syndrome (APS) in patients with and without SLE. 526 healthy controls and 1633 SLE and 1835 primary APS (PAPS) patients were evaluated. LAC was assessed by hexagonal phase phospholipid neutralization assay (HPPNA), diluted Russell viper venom test (dRVVT), and platelet neutralization procedure (PNP). ß2-glycoprotein-I and cardiolipin IgG, IgM, and IgA antibodies (aCL-IgG, aCL-IgM, aCL-IgA) were measured. 222/1633 SLE patients had APS based on the nine-test panel, which afforded the highest sensitivity (74%) and negative predictive value (90%) but lowest specificity (52%). HPPNA was the most sensitive individual test at 52%. The nine-test panel yielded the greatest sensitivity for aPL detection (70%) relative to HPPNA, the most sensitive individual test (36%) in PAPS. Superior sensitivity of a nine-test aPL panel has major implications for preventing potentially fatal thrombotic events in SLE and PAPS.

Probable catastrophic antiphospholipid syndrome secondary to chronic myelomonocytic leukaemia in an adult patient and a mini review.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening form of antiphospholipid syndrome (APS), which could be triggered by malignancy. Chronic myelomonocytic leukaemia (CMML) is an uncommon hematologic malignancy. We report a case of a 49-year-old male patient who presented multiple thromboses with a high titre of anti-ß2-glycoprotein-I antibody. Unexpectedly, there was persistent monocytosis combined with <20% blasts in his bone marrow. Thus, a diagnosis of probable CAPS and CMML was made. After treatment with prednisone, hydroxychloroquine and warfarin, the thromboses dissolved, and an improved presentation of peripheral blood and bone marrow was observed. Here, we also provide a mini review of cases of APS complicated with CMML identified from searches of MEDLINE, EMBASE and Web of Science databases. The review describes the clinical characteristics, laboratory data, treatments and outcomes.

Anti-ß2GPI antibodies enhance atherosclerosis in ApoE-deficient mice.

Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to ß2 glycoprotein I (anti-ß2GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of ß2GPI and anti-ß2GPI IgG, but this phenomenon has not been explored in vivo. Here, we present a mouse model to observe the effect of anti-ß2GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-ß2GPI IgG (100 µg/mouse) and homologous control IgG (100 µg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-ß2GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-ß2GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1ß, and MCP-1 were significantly increased in anti-ß2GPI IgG-treated mice. Together, these data indicate that anti-ß2GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.

Causes and factors related to hospitalizations in patients with systemic lupus erythematosus: analysis of a 20-year period (1995-2015) from a single referral centre in Catalonia.

INTRODUCTION: Although extensively characterized in the outpatient setting, systemic lupus erythematosus (SLE) in the hospitalization wards is still scarcely portrayed, particularly in the perspective of its evolution over the years. METHODS: Retrospective analysis of SLE patients hospitalized in the Department of Autoimmune Diseases of a university hospital during a 20-year period (1995-2015), describing hospitalization characteristics, causes and predictors of outcome. RESULTS: A total of 814 hospitalizations concerning 339 patients were analysed. The main causes of admission were flare (40.2%), infection (19.2%), diagnostic procedures (18.8%) and thrombotic events (5.4%). Therapy with cyclophosphamide (odds ratio (OR) 1.908, p = 0.047) was associated with admission due to infection, while antimalarials displayed a protective effect (OR 0.649, p = 0.024). Nearly 3.9% of patients required admission to an intensive care unit, with associated antiphospholipid syndrome (OR 7.385, p = 0.04) standing as a predicting factor for this outcome. Readmission at 30 days occurred in 5.8% of patients, with thrombocytopenia (OR 6.007, p = 0.002) and renal involvement (OR 3.362, p = 0.032) featuring as predicting factors. Eight patients died, with antiphospholipid syndrome (OR 26.814, p = 0.02) and thrombocytopenia (OR 31.523, p = 0.01) being associated with mortality. There was no significant variation in patients' demographics or admission causes across the 20-year period, except for a decrease in admissions due to thrombotic and musculoskeletal causes. Recently, an increase in the use of mycophenolate mofetil and lower doses of glucocorticoids were noted. CONCLUSION: While demographics of SLE hospitalizations have not markedly changed over the past 20 years, changes in therapy patterns were observed. Thrombocytopenia, antiphospholipid syndrome and renal involvement featured as predictors of poor outcome.

Clinical and immunological characteristics of antiphospholipid syndrome in an Asian population: a retrospective study.

OBJECTIVES: To describe the characteristics of patients with antiphospholipid syndrome (APS) in an Asian clinical practice setting. METHODS: We conducted a single-center, retrospective study of APS patients attending the rheumatology or hematology clinics, between January 2012 and December 2016. RESULTS: There were 450 patients suspected of having APS referred to our clinics. Seventy-four (16.4%) were diagnosed of APS, 51% of which were definite. Fifty-two (70%) patients were classified as primary APS, 50% of which were definite APS. The most common clinical manifestation was stroke (33%), followed by deep vein thrombosis of the lower extremities (30%) and pulmonary embolism (19%). Hypertension and the presence of at least one established cardiovascular risk factor were independently associated with stroke. Seven (9%) patients had multiorgan thrombosis as their first presentation of APS, 71% of which ultimately suffered from permanent organ damage or died of severe thrombosis, despite not fulfilling the criteria for 'definite' catastrophic APS (CAPS). Late fetal loss was the most prevalent obstetric complication. The majority of patients (79%) tested positive for lupus anticoagulant (LAC), while only 32% tested positive for anti-cardiolipin antibodies. Triple positive profile was documented in 14% of the cohort. Overall, recurrent thrombosis and bleeding complications were recorded in 9% and 28%, respectively. CONCLUSION: APS patients in central Thailand demonstrated high prevalence of stroke, late fetal loss, LAC positivity, and multiorgan thrombosis at first presentation, leading to poor outcomes.

Catastrophic antiphospholipid syndrome as a complication of systemic sclerosis.

A 62-year-old man with a history of systemic sclerosis was admitted with diffuse alveolar hemorrhage and acute kidney injury without clinical data suggestive of glomerulonephritis. Laboratory tests showed anemia, leukocytosis with neutrophilia, thrombocytopenia, elevated serum creatinine and metabolic acidosis. Antinuclear antibodies were positive at a titer of 1/640 (speckled, 1/160; nucleolar, 1/320) while rheumatoid factor, anti Scl-70, anti-centromere, anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane antibodies were negative and serum complement levels were within normal range. During the following days, the patient developed multiple organ failure and, eventually, died. Lupus anticoagulant was revealed positive after the patient's death, suggesting a catastrophic antiphospholipid syndrome. Clinical data and autopsy were consistent with this diagnosis.

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR).

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.

Unilateral localized conjunctival amyloidosis in a patient with a history of contralateral orbit/eyelid lymphoma.

Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is much more sensitive in diagnosing amyloidosis and can determine the type of amyloid deposit. Here we reported a case of conjunctival amyloidosis in a 52 year-old male patient who was presented with left lower eyelid swelling to our medical center. He has a complicated past medical history of anti-phospholipid antibody syndrome, Buerger's disease (thromboangitis obliterans), and small cell lymphoma (SLL) of the right orbit/eyelid. The patient received radiation to the right orbit to treat SLL with therapy completed one and a half years prior to presentation. Physical examination revealed a firm, raised yellowish colored lesion in the left lower conjunctiva. The conjunctival lesion was biopsied, and tissue sections were examined with Congo red stains and LC-MS/MS analysis. The biopsy showed amyloid deposits without evidence of malignancy, and the type of proteins in the deposit was immunoglobulin light chain (AL) of kappa type. A complete work up was taken for possible systemic involvement of amyloidosis and results were all negative. To our knowledge, this is the first case of localized conjunctival amyloidosis with a history of contralateral orbit/eyelid SLL.

Probable Catastrophic Antiphospholipid Syndrome with Intracerebral Hemorrhage Secondary to Epstein-Barr Viral Infection.

BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is a rare, severe variant of antiphospholipid syndrome with a high mortality rate. We report a unique case of CAPS secondary to Epstein-Barr viral (EBV) infection complicated by pulmonary and intracerebral hemorrhage. A review of the CAPS literature relevant to intensive care practice is used to outline a rational approach to diagnosis and management. METHODS: All data are from a single patient admitted to the Neurosciences Critical Care Unit in Addenbrooke's Hospital, Cambridge, in March 2016. Medline, Web of Science, PubMed, and the Cochrane Library were searched through September 2016 without restrictions for cases of CAPS, management of CAPS in the intensive care unit, and hemorrhage complicating CAPS. The patient gave express written consent to access and publish these data. RESULTS: This is only the second reported case of probable CAPS secondary to EBV infection. Furthermore, pulmonary and intracerebral hemorrhage is rare manifestations of this multisystem prothrombotic state which provided unique challenges to the management. CONCLUSIONS: While rare, CAPS should be considered in any patient presenting with rapidly progressive multiorgan failure, evidence of thrombotic microangiopathy, and antiphospholipid antibodies. A high index of suspicion is required as early, aggressive, multimodal treatment with anticoagulation, and immunosuppression improves outcomes.

[Life threatening manifestations of lupus and antiphospholipid syndrome in internal medicine]. / Zivot ohrozující projevy systémového lupusu a antifosfolipidového syndromu ve vnitrním lékarství.

The clinical picture of systemic lupus and antiphospholipid syndrome is remarkably varied and disease manifestations are commonly very heterogeneous. Relatively often both diseases are associated with severe, acute and life threatening manifestations, which places demands on the knowledge of differential diagnostics and experience of the physicians. This article deals with the serious and mostly acute impairment of cardiovascular, respiratory, renal, gastrointestinal, hematopoietic or nervous systems, briefly discusses the acute pregnancy complication and summarizes the basic therapeutic option. It emphasizes the role of both, sometimes inseparable, diseases in differential diagnosis of acute symptoms in internal medicine.Key words: clinical symptoms - diagnostics - live threatening manifestations - lupus erythematosus - systemic antiphospholipid syndrome - therapy.

Pathogenesis and management of antiphospholipid syndrome.

Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the 'antiphospholipid syndrome' (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I-specific anti-ß2-glycoprotein-I antibodies. This in turn has pointed to endothelial and complement activation as important factors in the pathogenesis of APS. Consequently, although anticoagulation remains the standard treatment for thrombotic APS and during pregnancy, the realisation that these additional pathways are involved in the pathogenesis of APS has significant implications for treatment: agents acting outside the coagulation system, such as hydroxychloroquine for pregnancy complications and sirolimus as an inhibitor of the mammalian target of rapamycin (mTOR) pathway, are now under evaluation and represent a radical change in thinking for haematologists. Conventional anticoagulation is also under challenge from new, direct acting anticoagulants. This review will provide a comprehensive overview of the evolving understanding of APS pathogenesis and how this and novel therapeutics will alter diagnosis and management.

Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.

Prognostic significance of renal vascular pathology in lupus nephritis.

We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.

Detrimental roles of TNF-alpha in the antiphospholipid syndrome and de novo synthesis of antiphospholipid antibodies induced by biopharmaceuticals against TNF-alpha.

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by arterial and/or venous thrombosis and/or recurrent pregnancy losses. Obstetric APS (OAPS) is considered as a distinct entity from vascular APS (VAPS). In the absence of any additional disease, APS is designated as primary (PAPS), while the term secondary APS (SAPS) is used when other diseases are associated. Catastrophic APS (CAPS) is characterized by the rapid development of multiple thrombosis in various vital organs. The presence of antiphospholipid antibodies (aPL Abs) is considered as a laboratory criterion for APS diagnosis. aPL Abs cause an increase in systemic and decidual TNF-alpha levels in experimental model of APS (eAPS), while paradoxically, administration of TNF-alpha blockers has been associated with de novo synthesis of aPL Abs in patients with various autoimmune diseases. While eAPS provides evidence for the fact that application of TNF-alpha blockers has beneficial effects, lack of randomized prospective studies is the main obstacle for consideration of TNF-alpha blockers administration as a therapeutic option not for all, but at least for selected cases of APS patients despite compelling evidence for detrimental roles of TNF-alpha for both VASP and OAPS. This article represents a review of previously published reports on detrimental roles of TNF-alpha in APS, reports on the application of anti-TNF-alpha agents in eAPS and articles that reported de novo synthesis of aPL Abs induced by biopharmaceuticals against TNF-alpha.

[Recurrent thromboembolisms despite full anticoagulation in a patient with antiphospholipid syndrome]. / Rezidivierende Thrombembolien trotz Vollantikoagulation bei Patientin mit Antiphospholipidsyndrom.

We report on a female patient with confirmed secondary antiphospholipid syndrome (APS) due to underlying systemic lupus erythematosus (SLE). Despite a thromboplastin time within the normal range (international normalized ratio, INR) under treatment with a vitamin K antagonist (VKA), a recurrent thrombotic event occurred, this time as pulmonary embolism due to bilateral deep vein thrombosis. Despite an INR value in the therapeutic range, clotting factors II, VII, IX and X were found to be insufficiently decreased suggesting inefficient anticoagulation. Thus, the anticoagulation regimen was changed to the direct oral anticoagulant dabigatran. This case demonstrates that the INR in APS patients may be artificially prolonged in rare cases, despite a normal activated partial thromboplastin time (aPTT) and cannot be used for monitoring VKA anticoagulant therapy. Suspicion of ineffective anticoagulation despite VKA therapy should prompt measurement of the individual clotting factors.

Antiphospholipid Antibody Syndrome With Valvular Vegetations in Acute Q Fever.

BACKGROUND: Coxiella burnetii endocarditis is considered to be a late complication of Q fever in patients with preexisting valvular heart disease (VHD). We observed a large transient aortic vegetation in a patient with acute Q fever and high levels of IgG anticardiolipin antibodies (IgG aCL). Therefore, we sought to determine how commonly acute Q fever could cause valvular vegetations associated with antiphospholipid antibody syndrome, which would be a new clinical entity. METHODS: We performed a consecutive case series between January 2007 and April 2014 at the French National Referral Center for Q fever. Age, sex, history of VHD, immunosuppression, and IgG aCL assessed by enzyme-linked immunosorbent assay were tested as potential predictors. RESULTS: Of the 759 patients with acute Q fever and available echocardiographic results, 9 (1.2%) were considered to have acute Q fever endocarditis, none of whom had a previously known VHD. After multiple adjustment, very high IgG aCL levels (>100 immunoglobulin G-type phospholipid units; relative risk [RR], 24.9 [95% confidence interval {CI}, 4.5-140.2]; P = .002) and immunosuppression (RR, 10.1 [95% CI, 3.0-32.4]; P = .002) were independently associated with acute Q fever endocarditis. CONCLUSIONS: Antiphospholipid antibody syndrome with valvular vegetations in acute Q fever is a new clinical entity. This would suggest the value of systematically testing for C. burnetii in antiphospholipid-associated cardiac valve disease, and performing early echocardiography and antiphospholipid dosages in patients with acute Q fever.