Identifying phenotypes of patients with antiphospholipid antibodies: results from a cluster analysis in a large cohort of patients.

OBJECTIVES: To identify the aggregation of patients with aPL into different subgroups sharing common features in terms of clinical and laboratory phenotypes. METHODS: We applied a hierarchical cluster analysis from the multiple correspondence analysis to determine subgroups of patients according to clinical and laboratory characteristics in a cohort of subjects with confirmed aPL positivity who presented to our outpatient clinics from 2006 to 2018. RESULTS: A total of 486 patients [403 women; age 41.7 years (26)] were included, resulting in five clusters. Cluster 1 (n= 150) presented with thrombotic events (65.3% with venous thrombosis), with triple aPL positivity found in 34.7% of them (the highest rate among the different clusters). All the patients from cluster 2 (n = 91) had a confirmed diagnosis of SLE and the highest rate of anti-dsDNA positivity (91.7%). Cluster 3 included 79 women with pregnancy morbidity. Triple positivity was present in 3.8%, significantly lower when compared with Cluster 1 (34.7% versus 3.8%, P <0.01). Cluster 4 included 67 patients, 28 (41.8%) of whom with APS. Thrombotic events were observed in 23.9% patients. Cluster 4 had the highest rate of cytopenia, with thrombocytopenia as high 41.8% with no anti-dsDNA antibodies. Cluster 5 included 94 asymptomatic aPL carriers. CONCLUSION: While clusters 1, 2, 3 and 5 corresponded to well-known entities, cluster 4 might represent a bridging condition between pure primary APS and defined SLE, with lower thrombotic risk when compared with primary APS but higher general features such as ANA and cytopenia (mainly thrombocytopenia).

Resolutive pulmonary endarterectomy in a non-compliant patient with systemic lupus erythematosus and antiphospholipid syndrome.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have poor prognosis, and pulmonary endarterectomy (PEA) is considered the treatment of choice for this condition. We report a case and review the literature of successful PEA for CTEPH due to antiphospholipid syndrome associated with systemic lupus erythematosus. The definitive and decisive approach needed to treat this high-risk patient with a history of comorbidity, long-term illness and poor compliance was found with a therapy of PEA.

8-isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as markers of inflammation and oxidative stress in antiphospholipid syndrome: a pilot study.

OBJECTIVE: To test the inflammation and oxidative stress hypothesis in antiphospholipid syndrome (APS) patients and to identify possible associations with clinical and laboratory features of the disease. METHODS: Serum amyloid A (SAA), C-reactive protein (CRP), 8-isoprostane and prostaglandin E2 (PGE) were assayed in the sera of 45 APS patients and then compared to control groups made up of 15 antiphospholipid antibody (aPL) negative patients with systemic lupus erythematosus, 15 aPL negative subjects with pregnancy-related morbidity, 15 aPL negative patients with thrombosis, 15 subjects with persistently positive aPL with no signs or symptoms of APS, and 15 healthy volunteers from among the hospital staff. RESULTS: APS patients showed significantly higher CRP (p = 0.01), SAA (p < 0.01), 8-isoprostane (p = 0.05) and PGE2 (p = 0.001) plasma levels as compared to controls. Among APS subjects, significantly higher 8-isoprostane and PGE2 levels were observed in patients with triple positivity for aPL (lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies) compared to APS patients with single or double aPL positivity. CONCLUSION: Both inflammation and oxidative stress, as measured by SAA, CRP, 8-isoprostane and PGE2, occur in APS and seem to be related to triple positivity for aPL.

Antiphospholipid Antibodies and Infection: Non Nova Sed Nove.

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.

Inherited thrombophilia in women with poor aPL-related obstetric history: prevalence and outcomes. Survey of 208 cases from the European Registry on Obstetric Antiphospholipid Syndrome cohort.

AIM: To analyse the prevalence and effects of inherited thrombophilic disorders (ITD) on maternal-foetal outcomes in cases of antiphospholipid antibody related to obstetric complications. METHODS: Women with obstetric complaints who tested positive for aPL and with inherited thrombophilia were prospectively and retrospectively included. RESULTS: ITD data were available in 208 of 338: 147 had obstetric antiphospholipid syndrome (OAPS) and 61 aPL-related obstetric morbidity (OMAPS). 24.1% had ITD. Laboratory categories I and IIa were more related to OAPS-ITD and IIb and IIc to OMAPS-ITD. No significant differences in obstetric complaints were observed. Regarding ITD carriers, treatment rates were higher in OAPS than in OMAPS for LMWH and LDA plus LMWH (P=.002). CONCLUSION: Cases with aPL-related OAPS/OMAPS showed no differences in maternal-foetal outcomes regardless of the presence of one ITD. Maternal thrombotic risk was low, with ITD-positive cases included. Registry data concur with Sydney criteria, whereby aPL-ITD-positive patients are classified as having antiphospholipid syndrome.

Bridging therapy in antiphospholipid syndrome and antiphospholipid antibodies carriers: case series and review of the literature.

Peri-operative management of patients on warfarin involves assessing and balancing individual risks for thromboembolism and bleeding. The timing of warfarin withdrawal and a tailored pre/postoperative management (including the substitution of heparin in place of warfarin, the so-called bridging therapy) is critical in patients with prothrombotic conditions. The antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia. In this particular subset of patients, as the risk of thrombosis is higher than in general population, bridging therapy can represent a real challenge for treating physicians. Only few studies have been designed to address this topic. We aim to report our experience and to review the available literature in the peri-procedural management of APS and antiphospholipid antibody-positive patients, reporting adverse events and attempting to identify potential risk factor associated with thrombosis or bleeding complications.

Predictors of cardiovascular events in patients with systemic lupus erythematosus (SLE): a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease represents an important cause of morbidity and mortality in patients with a diagnosis of systemic lupus erythematosus (SLE), due to a complex interplay between traditional risk factors and disregulation of autoimmunity but uncertainty is still present about the most important predictors of cardiovascular events. OBJECTIVES: The aim of our work was to perform a collaborative systematic review on the main predictors of cardiovascular events in SLE patients. METHODS: PubMed and Cochrane were systematically searched for eligible studies on SLE and cardiovascular events between January 2008 and December 2012. Study features, patient characteristics and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate - 95% confidence intervals) and consistency of predictors was formally appraised. RESULTS: A total of 17,187 patients was included; of those, 93.1% were female and the median age was 39 years. After a median follow-up period of 8 years, cardiovascular events presented in 25.4%, including acute myocardial infarction (4.1%) and stroke (7.3%). The most important predictors may be divided into traditional risk factors, such as male gender (OR 6.2, CI 95% 1.49-25), hyperlipidaemia (OR 3.9, CI 95% 1.57-9.71), familiar history of cardiac disease (OR 3.6, CI 95% 1.15-11.32) and hypertension (OR 3.5, CI 95% 1.65-7.54), and SLE-related features, such as the presence of auto-antibodies (OR 5.8 and 5.0, CI 95% 3.28-7.78) and neurological disorders (OR 5.2, CI 95% 2.0-13.9). A low correlation was shown for the importance of organ damage and SLE activity (respectively OR 1.4, CI 95% 1.09-4.44 and OR 1.2, CI 95% 1.2-1.2), as well as for age at diagnosis (OR 1.1, CI 95% 1.07-1.17). CONCLUSIONS: Cardiovascular events in SLE patients are caused by a multifactorial mechanism, including both traditional and disease-specific risk factors. A global valuation with an individual risk stratification based on both these features is important to correctly manage these patients in order to reduce negative outcomes.

Primary lymphoma of the heart. A case report and review of the literature.

Primary cardiac lymphoma (PCL) is a rare and usually fatal neoplasm, which may cause syncope, arrhythmia, heart failure and pericardial effusion as presenting clinical complaints. A case of PCL in a 72-year-old man with moderate aortic stenosis is presented. The patient was investigated because of pericardial effusion and diagnosis of diffuse large B-cell lymphoma was obtained by open-chest biopsy of the heart. Fatal ventricular arrhythmia developed the day after the first course of chemotherapy. Clinical presentations and diagnostic approach of this rare tumour are discussed. While chemotherapy is the only effective treatment of PCL, early post-chemotherapy phase should be considered critical in patients with PCL, as suggested by other reported fatal complications in this period.

Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. A European multicentre retrospective study.

Previous thrombosis, diagnosis of systemic lupus erythematosus (SLE) and triple antiphospholipid (aPL) antibody positivity have recently been found to be independent factors associated to pregnancy failure during conventional therapy in women with antiphospholipid syndrome (APS). This study aimed to assess the effect of various treatment strategies on pregnancy outcomes in women with APS and the risk factors for pregnancy failure. One hundred ninety-six pregnancies of 156 patients diagnosed with APS were analysed: 118 (60.2%) of these had previous thrombosis, 81 (41.3%) were diagnosed with SLE, and 107 (54.6%) had triple aPL positivity. One hundred seventy-five (89.3%) were treated with conventional therapies (low-dose aspirin [LDA] or prophylactic doses of heparin + LDA or therapeutic doses of heparin + LDA), while 21 (10.7%) were prescribed other treatments in addition to conventional therapy. The pregnancies were classified into seven risk profiles depending on the patients' risk factors - thrombosis, SLE, and triple aPL positivity - and their single, double or triple combinations. It was possible to find significant difference in outcomes correlated to treatments only in the thrombosis plus triple aPL positivity subset, and logistic regression analysis showed that additional treatments were the only independent factor associated to a favourable pregnancy outcome (odds ratio=9.7, 95% confidence interval=1.1-88.9, p-value<0.05). On the basis of this retrospective study, we found that APS pregnant patients with thrombosis and triple aPL positivity treated with additional therapy had a significant higher live-birth rate with respect to those receiving conventional therapy alone.