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INTRODUCTION: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS). METHODS: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months. RESULTS: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles. CONCLUSION: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Limitations in the data used to define thromboprophylaxis for patients with antiphospholipid antibodies (aPLAbs) and thrombosis include uncertainties after an initial provoked venous thromboembolic event (VTE). We aimed to study such cases associated with combined oral contraceptive (COC) intake.We retrospectively analysed thrombotic outcomes after a first COC-associated VTE and positive aPLAbs, with a low risk HERDOO2 score, on low-dose aspirin (LDA) secondary thromboprophylaxis, seen from 2010 to 2021 in 3 tertiary referral centres, one in France and 2 in Russia. Data from 264 patients (distal deep vein thrombosis DVT: 62.9 %), cumulating in 1327.7 patient-years of observation, were collected.There were 22 cases of thrombosis: 16 distal DVTs, 3 proximal, 1 pulmonary embolism (PE) and 2 transient ischemic attacks. Recurrence rate was 1.66 per 100 patient-years (p-y; 95 % CI: 0.96-2.33). No major bleeding occurred. Risk factors affecting recurrence-free survival were the time between first COC intake and VTE (p 0.0001; the shortest, the lower), proximal DVT (p = 0.021), active smoking (p = 0.039), an associated systemic disease (p = 0.043) and circulating monocyte counts (p = 0.001).We observed a low risk of recurrence which was modulated by classical risk factors for VTE. These observational data may provide clues for future randomized controlled trials.

The antiphospholipid syndrome (APS) is the most common cause of acquired immune-mediated thrombophilia. This syndrome is broadly defined by the presence of arterial or venous thrombosis, or pregnancy morbidity, in the presence of high levels of antiphospholipid antibodies. Despite recognition of this disorder more than 50 years ago, a fundamental unifying pathogenesis has not been determined. Due to this, mechanism-based therapies for APS are not available, and current management following thrombotic events suggests anticoagulation of indeterminate duration, or for obstetric complications, heparin/low molecular weight heparin and aspirin. However, APS is an autoimmune disorder, and several approaches focused on modulating the immune response or its effectors have been employed. Those which have been most extensively studied include hydroxychloroquine, rituximab and eculizumab, an inhibitor of complement C5. In this report, we review in depth, and critique, key clinical studies of these agents. Since all of these studies are small, our conclusions are qualified. However, it appears that hydroxychloroquine may enhance the anticoagulant efficacy of vitamin K antagonists in APS patients, and that rituximab may ameliorate some of the "non-criteria" manifestations of APS. The catastrophic antiphospholipid syndrome (CAPS) is associated with diffuse thrombosis, multi-organ dysfunction, and ∼30% mortality. A high incidence of complement regulatory gene mutations, and compelling data concerning the efficacy of eculizumab in CAPS, suggests an important role for complement in this disorder. However, additional work is needed to clarify the role of complement in non-catastrophic APS, though emerging data suggests that complement inhibition may be effective in preventing thrombosis in these patients as well.

We aimed to apply and compare the QRISK3 and the adjusted Global AntiPhospholipid Syndrome (APS) Score (aGAPSS) in a cohort of systemic lupus erythematosus (SLE) patients, with and without a concomitant diagnosis of APS, in order to assess their augmented risk of developing cardiovascular diseases (CVDs).Patients (25-85 yo) with a diagnosis of SLE and/or of Secondary APS (SAPS) were included. QRISK3 was calculated using the official online calculator; aGAPSS using the validated point-values based on aPL-profile and independent risk factors.The cohort included 142 SLE patients: 34 SAPS (23.9%) and 108 SLE patients without APS (76.1%).When considering all the cohort, patients with cerebrovascular/coronary events showed higher values of aGAPSS (10.1 ± 6.2 vs. 5.8 ± 6.1; p = 0.007), but not of the QRISK3. Furthermore, a significant association was observed between the occurrence of these events and high-risk aGAPSS: p = 0.03 for aGAPSS≥8, p = 0.01 for aGAPSS ≥9, p = 0.008 for aGAPSS ≥10. aGAPSS strongly correlated with the occurrence of any thrombotic event, both at the uni- and multivariate analysis (p = 0.012 and p = 0.009). Male gender also resulted to positively correlate with the occurrence of any thrombotic event at both uni- and multivariate analysis (p = 0.017 and p = 0.03). Focusing on aPL-profile, regardless the diagnosis, we found a statistical significance only for aGAPSS (aPL+ =9.6 ± 6.3 vs. aPL- = 4.1 ± 5.1; p 0.001).Despite QRISK3 being more accurate than traditional risk score in predicting CVD risk in SLE patients, aGAPSS appears to be the most valuable tool for this purpose.

Anti-phosphatidylserine prothrombin antibodies (aPSPT) are reported to be highly associated with the lupus anticoagulant (LAC) in established antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) cohorts. Further, aPSPT has been suggested to be a useful surrogate LAC marker. However, validation studies replicating this relationship in an all-comer study population in the diagnostic clinical setting are lacking.To determine the sensitivity and specificity of aPSPT to the LAC in an all-comer population undergoing evaluation for suspected APS.An assembled cross-sectional cohort from June 2017 to December 2018 undergoing APS evaluations across all medical specialties were reviewed for LAC, aPSPT, anti-cardiolipin (aCL), and anti-β2 glycoprotein-1 (β2GP1). Sensitivities, specificities, and negative and positive predictive values were calculated.A cohort of 166 eligible patients was identified. Seventy-one percent were female, 89% White, 15% with SLE, and 21% with APS. The aPSPT was found to be the most specific to the LAC. Specificity of IgG aPSPT was 100% (96%-100%) and IgM aPSPT was 97% (91%-100%) to the LAC. Corresponding positive predictive value for IgG aPSPT was 100% (89%-100%) and IgM aPSPT was 95% (84%-99%). In contrast, the sensitivities of aPSPT to the LAC were less robust, only in the 40%-50% range. The findings validate previously reported findings and lends extension to an all-comer population. These findings corroborate aPSPT as a potentially useful clinical marker of the LAC.

Background Pregnancy in women with systemic lupus erythematosus (SLE) and nephritis (LN) is at risk of foetal and maternal complications. Objective To evaluate the effect of LN on pregnancy with respect to foetal and maternal outcome. Methods We retrospectively studied all pregnant SLE patients with and without diagnosis of LN, who attended the Materno Neonatal Hospital in Cordoba city, Argentina, from January 2015 to April 2017. Demographic, clinical, and laboratory data were collected. The presence of antiphospholipid syndrome (APS) and antiphospholipid antibodies (AAF), and maternal and foetal outcome were evaluated. Results 121 pregnancies in 79 patients were included. Pregnancies were divided into those with LN (69) and those without LN (52). The presence of APS and AAF was more frequent in the LN group as well as higher basal SLEDAI. The LN group received more immunosuppressive therapy and increased steroid dose treatment. Of the patients, 47.5% had Class IV LN. Lupus flares occurred more frequently in the LN group 25.8% vs 10.9% in the group without LN (P = .041), mainly renal flares in the LN group. No patients developed end-stage renal failure. Preeclampsia was more frequent in the LN group, 18.8% vs 6.3% in the group without LN (P = .047). There was only one maternal death. A caesarean section was required in 68.5% of the LN group vs 31.5 in the group without LN, and urgent caesarean section was also performed in the LN group. There were no differences in foetal outcomes in either group: live birth, gestational age, weight birth, perinatal death, foetal distress. Conclusions Patients with LN experienced more maternal complications such as lupus flares and preeclampsia. However, LN does not lead to a worse pregnancy and foetal outcome. Patients should be strictly monitored before and after conception.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of aPLs with thrombotic events depends on the number of positive tests. Besides the three classical tests to classify APS, phosphatidylserine/prothrombin complex autoantibodies (aPS/PT) are increasingly used to better define this condition. The aim of this systematic review was to evaluate the prevalence of aPS/PT in general and according to antiphospholipid antibody profiles in patients with APS.A systematic search of PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021 was carried out according to PRISMA guidelines. Proportions and 95% confidence intervals (CIs) were calculated using random-effects model. Publication biases were evaluated via visualization of funnel plots along with Egger's and Begg's tests.Twenty-one articles about the prevalence of aPS/PT in 1853 patients with APS were deemed eligible and analyzed according to the inclusion criteria. Pooled prevalence of aPS/PT IgG alone, IgM alone, and IgG/M were 50.0%, 45.0%, and 65.0%, respectively. No significant publication bias was detected from funnel plots or Egger's and Begg's tests. When the prevalence of aPS/PT was calculated in homogeneous aPLs, a much higher rate of pooled prevalence of aPS/PT IgG/M in patients positive for Lupus Anticoagulant (84.5%) and in those with triple positivity (83.4%) was found.These data show a high rate of aPS/PT positivity in patients with APS (especially in those positive for LAC) but further studies are needed to ascertain whether this test might be useful in the laboratory classification criteria of APS.

The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.

Direct oral anticoagulants recently became the first-line choice for anticoagulation in venous thromboembolic disease. Many studies have shown its non-inferiority regarding the risk of thromboembolic recurrence compared to anti-vitamin K without increasing the risk of bleeding in the general population. However, specific populations such as patients with cancer, patients with kidney failure, patients with constitutional thrombophilia, elderly patients, or patients with extreme weight are at risk of intolerance to the use of direct oral anticoagulants. Precautions in use may be necessary as discussed in recently published guidelines about antiphospholipid syndrome. This review aims to list the main clinical trials investigating direct oral anticoagulants in venous thromboembolic disease in the general population and populations at risk, as well as to provide an update on current international and French guidelines.

Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).

Antiphospholipid antibodies (aPL) have been reported not only in various autoimmune conditions but also in other infections, such as chronic hepatitis C (CHC) infection. The aim of this study is to evaluate the frequency of aPL in patients with CHC.Ninety-six CHC patients and 90 healthy blood donors (HBD) were studied. Fifty-three of the patients were under treatment, and 43 had not yet received any treatment. IgG, IgA, and IgM antibodies against cardiolipin (aCL) and beta-2 glycoprotein I (aβ2GPI) were detected by ELISA.We found that the frequency of aPL (aCL and/or aβ2GPI) was significantly higher in CHC patients than in controls (51% vs 11.1%, p 10On the basis of the findings of this study, aPL, particularly aβ2GPI-IgA and aCL-IgG, are frequent in CHC patients.

Background ABCB4-gene mutations are responsible for several cholestatic diseases with a heterogeneous clinical spectrum. Aims To analyse phenotype/genotype relationships in ABCB4-mutations. Methods Retrospective characterization of adult patients with ABCB4-variations diagnosed between 2015 and 2020. Genotype-phenotype correlations were analysed and compared with previously reported data. Results Twenty patients from 12 families were included. Thirteen patients presented recurrent elevated liver tests, eight fulfilled Low-Phospholipid-Associated-Cholelithiasis syndrome criteria, five had Intrahepatic Cholestasis of Pregnancy and three patients developed Drug-Induced-Liver-Injury. ABCB4 screening identified eight different mutations. Five patients were homozygotes to the variant c.504T > C. Ten patients had one mutation in heterozygote-state and five patients had two mutations in compound- heterozygosity . Portal fibrosis occurred in two patients. One of these patients presented progressive fibrosis and progression of cholestasis despite ursodeoxycholic-acid treatment, this patient also harbours a ABCB11 polymorphism. Conclusion Although, phenotype-genotype relationships have not been clearly defined, an early diagnosis of ABCB4-variants may have an important role in management decisions and patient outcomes. To our knowledge, we describe a not previously reported deletion (c.1181delT) in ABCB4. The c.504T > C polymorphism, although a silent mutation at the protein level, seems to be associated to different cholestatic diseases. The role of other genes variants, namely ABCB11, as co-factor for progression, needs to be clarified.

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by venous or arterial thrombosis, and/or pregnancy loss or complications in the presence of persistently positive antiphospholipid antibodies. Organ involvement, referred to as non-criteria manifestations, includes livedo reticularis, thrombocytopenia and nephropathy. Non-thrombotic inflammatory mechanisms are increasingly identified in the pathogenesis of APS, alongside a recognition that obstetric APS might be a specific subset of APS. Treatment remains focused on life-long anticoagulation and prevention of further thrombosis or obstetric complications. Identification of novel mechanisms is, however, leading the development of diagnostic tests and more targeted therapies to improve disease management.

International audience; Background Although the triple positivity of antiphospholipid antibodies (aPL) is important for classifying high-risk patients, interpretation of aPL positivity, namely the lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I autoantibodies (aB2GPI) remains challenging for thrombotic risk stratification. Objective To compare biological and clinical data between triple aPL- and single aCL-positive patients. Methods Of the 6500 patients assayed for aPL in daily practice within 3 years, we retrospectively analyzed data from 161 patients that were either triple aPL-positive or single aCL-positive with 5 years' follow-up for 121 of them. Results Whatever triple or single aPL positivity, we found a high prevalence of "carrier" patients (43%), which led us to question the clinical relevance of the triple aPL positivity. This result also justified the need to identify high-risk profiles. In asymptomatic patients, high risk of thrombotic events is associated with (1) two positive tests for LA or a Rosner Index >27 combined with both aCL-IgG and aB2GPI-IgG positivity, (2) persistent single aCL positivity without an associated autoimmune disease. In symptomatic patients, we demonstrated differences in the phenotype of patients and their therapeutic anticoagulation according to the number of positive aPL but we did not find differences in the number of clinical events, recurrence, or relapse, even in the absence of treatment. Conclusion This study shows that the thrombotic risk does not necessarily increase with the number of positive tests and raises the question of the therapeutic management of single aCL-positive patients.

Thrombin generation assay (TGA) is a useful tool to evaluate the initiation, propagation and inhibition of coagulation. TGA is a global test that is used to assess hemorrhagic risk in hemophilia patients, but it can also be used to study hypercoagulable states. The interest of TGA is to screen for cardiovascular risk, which is regularly associated with autoimmune disease (AID) such as antiphospholipid syndrome. Indeed, TGA has been used to evaluate hypercoagulability in patients with antiphospholipid syndrome treated with rivaroxaban versus warfarin. In other AIDs without thrombotic events, TGA measurement is elevated, mainly in rheumatoid arthritis (RA), systemic lupus erythematosus and Behcet's disease. These findings in RA are correlated with the inflammatory activity of the disease. In systemic lupus erythematosus and Behcet's disease, TGA appears to reflect disease activity. In conclusion, TGA remains relatively under used in the clinical evaluation of AID, but it could play a greater role in the evaluation of certain potentially thrombogenic treatments in AID. Finally, TGA helps measuring AID activity, due to the clearlink between coagulation and inflammation, despite some limitations of interpretation mainly due to a lack of standardization.

Objective The aim of this study was to analyze patients with thrombophilia who underwent oral and/or maxillofacial surgery at our center. Study Design We performed a retrospective analysis of patients with hereditary or acquired thrombophilia who had undergone oral/maxillofacial surgery between January 1, 2000 and December 31, 2019. Data regarding demographic and patient characteristics, surgical treatment modalities, antithrombotic therapies, and complications were analyzed. Results A total of 76 eligible patients (26 male, 50 female) were included in this study, with a mean follow-up period of 3.8 months (range, 0-51 months). The mean age at time of surgery was 44.7 ± 19.4 years. Seven different hereditary and acquired thrombophilia were identified: factor V Leiden (n = 31; 40.8%), prothrombin G20210A mutation (n = 5; 6.6%), protein C deficiency (n = 4; 5.3%), protein S deficiency (n = 11; 14.5%), antiphospholipid syndrome (n = 10; 13.2%), hyperhomocysteinemia (n = 8; 10.5%), and elevated factor VIII (n = 2; 2.6%). Complications occurred in 9 patients (11.8%) and included postoperative infections (n = 6; 7.9%) and postoperative bleeding (n = 3; 3.9%). Conclusion Our data suggest that oral and/or maxillofacial surgery in patients with a confirmed diagnosis of thrombophilia is not associated with a burden of thrombosis or high complication rates. Furthermore, we formulated a guideline for preoperative antithrombotic therapy for patients with thrombophilia undergoing oral and/or maxillofacial surgery.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory syndrome characterized by diffuse inflammatory manifestations, predisposition to hematological malignancy, and an association with a high rate of thrombosis. VEXAS is attributed to somatic mutations in the UBA1 gene in hematopoietic stem and progenitor cells with myeloid restriction in mature forms. The rate of thrombosis in VEXAS patients is approximately 40% in all reported cases to date. Venous thromboembolism predominates thrombotic events in VEXAS. These are classified as unprovoked in etiology, although systemic and vascular inflammation are implicated. Here, we review the clinical and laboratory characteristics in VEXAS that provide insight into the possible mechanisms leading to thrombosis. We present knowledge gaps in the mechanisms and management of VEXAS-associated thromboinflammation and propose areas for future investigation in the field.

Background and aims Autoimmune diseases (AID) share various clinical signs and symptoms and pathophysiological mechanisms including the increased risk of cardiovascular disease. The coronary artery calcium score (CACS) is potentially useful in improving the cardiovascular risk assessment. The aim of this study was to evaluate CACS in six AIDs analyzed as a group compared with controls through a systematic literature review (SLR) and meta-analysis. Methods A literature search (Medline/OVID, Lilacs, Embase, and Cochrane/OVID) up to January 6, 2021 was made (PROSPERO CRD42020197182). Observational studies (patients with six AIDs: rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], Sjogren's syndrome, systemic sclerosis, dermatopolymyositis, and antiphospholipid syndrome) compared with controls were included. CACS, reported in Agatston units, was the primary outcome in both groups. Mean differences and a random-effects model (DerSimonian and Laird) were calculated. Results Nineteen articles were meta-analyzed (4568 subjects: 2142 AID and 2426 controls). Mean age was 48.1 and 44.2 years, respectively and 75.6% and 84.9% were women, respectively. Of cases, 52.9% had RA, 44.4% SLE and 2.7% had systemic sclerosis. The pooled analysis showed a higher CACS in patients with AIDs (7.42; 95% CI 1.79 to 13.05; chi2-p = 0.01) compared with controls. Meta-regression models showed that age in cases and controls reduced the difference in CACS between groups (p Conclusions The quantitative results of this meta-analysis suggest that CACS is higher in patients with AID, possibly due to chronic exposure to pro-inflammatory molecules. These results have clinical implications since the finding of highly elevated CACS in patients with AID will enable physicians and researchers to develop a risk stratification model that includes CACS as one of the screening tools for detecting coronary atherosclerosis in these patients.

Objective To investigate the neonatal and maternal outcomes of patients treated with belimumab during pregnancy. Materials and methods We retrospectively collected patients who were treated with belimumab during pregnancy from January 2018 to October 2020 in a tertiary referral hospital in Taiwan. All patients had clinical and serological features of systemic lupus erythematosus or antiphospholipid syndrome and had been treated accordingly. The patients’ medical and obstetric history, obstetric complications and fetal outcomes were collected by chart review. Results A total of 13 pregnancies in 13 patients were included. The median age was 38 years (interquartile range 32–41 years), 46.2% had a history of recurrent pregnancy loss, and the median number of treatment courses with belimumab (400 mg per dose) was two. There were 11 live births (84.6%, 11 of 13). One episode of omphalitis was noted in one fetus, who recovered well with antibiotic treatment. No fetus had leukopenia, lymphopenia, neutropenia, or thrombocytopenia in the days after birth. No fetal anomalies were found in this series. Among the six patients with a past history of recurrent pregnancy loss, four had live births. Conclusion This study provides new evidence for the use of belimumab in pregnant patients. No increase in the risk of fetal anomalies or severe infection was noted in the patients who were exposed to belimumab during pregnancy. Cautious monitoring is necessary if belimumab is used in pregnant patients, and more data are still needed to validate its safety.

Immune checkpoint inhibitors (ICI) improve the prognosis of patients with advanced non-small cell lung cancer. However, clinicians should be aware of potentially life-threatening immune-related adverse events (irAEs). We report a case of a 67-year-old man with lung adenocarcinoma who developed an acute ischemic stroke after the second administration of pembrolizumab. The patient benefited from thrombolysis and mechanical thrombectomy with improved neurological outcome. An anti-phospholipid syndrome (APS) was diagnosed. Simultaneously, he developed a grade IV autoimmune hepatitis. Both manifestations were considered irAEs and the ICI treatment was discontinued. Steroids were initiated resulting in irAEs resolution. Remarkably, the patient achieved a complete oncological response and persistent remission after one year follow-up despite early discontinuation of pembrolizumab. Of note, APS is rarely reported as irAE. To our knowledge, this is the first case reported in the context of lung cancer. A systematic review of the literature is provided., SCOPUS: re.j, info:eu-repo/semantics/published

Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndrome–coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID‐19. Results We here demonstrate that lipid‐binding aPL are common in COVID‐19. COVID‐19 patients with lipid‐binding aPL have higher median concentrations of C‐reactive protein and D‐dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid‐binding aPL isolated from COVID‐19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid‐reactive aPL of the IgG isotype circulate in the blood of COVID‐19 patients. In vivo, COVID‐19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR‐LBPA. Conclusions COVID‐19 patients rapidly expand B1a cells secreting pathogenic lipid‐binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID‐19–associated coagulopathy.

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon and the most severe form of antiphospholipid syndrome (APS). A 33-week pregnant patient with Klippel-Trenaunay syndrome, past SARS-CoV-2 infection and type I fetal growth restriction with shortening of the fetal long bone was diagnosed in our center with a probable CAPS. Cesarean section was performed four days after the diagnosis due to the torpid evolution of the patient. Clinical improvement was noted a few days later and the mother and baby were discharged within a week. We review the current literature on CAPS during pregnancy and provide an updated view.

Background Lupus anticoagulant (LA)-detection in anticoagulated patients is an unmet need, which becomes even more cogent with the introduction of direct oral anticoagulants (DOAC) that may lead to false-positive results. Aims We aimed to investigate the effect of a commercially available DOAC absorbent on residual drug concentrations, and on integrated procedures for LA-detection. Methods Blood from patients treated for atrial fibrillation with either dabigatran (n = 39), rivaroxaban (n = 55), apixaban (n = 47) or edoxaban (n = 47) were collected at peak and trough, and centralized for testing with two LA integrated procedures [i.e., the silica clotting time (SCT) and dilute Russel viper venom (dRVVT)] before and after DOAC absorbent exposure. Results The commercially available DOAC absorbent investigated in this study proved effective in reducing the concentrations of all the investigated DOAC, although small residual drug was detected after absorption, especially in patients on edoxaban. Results mimicking LA were observed in patients on DOAC before absorbent exposure, especially for rivaroxaban when testing was performed with dRVVT (88% rate at peak and 20% at trough) and much less with SCT (12% at peak and 8% at trough). The correspondent rate of results mimicking LA in patients on rivaroxaban after exposure was reduced [dRVVT (peak 8%, trough 4%); SCT (peak and trough 8%)], but not abolished. Conclusions Overall, in vitro DOAC absorbance by active charcoal compounds is a useful laboratory tool for LA-detection in patients on DOAC. Caution should however be exerted when used in daily practice.

To assess the mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), the neutrophil-to-lymphocyte ratio (NLR) and the MPV-to-lymphocyte ratio, and to test them according to the clinical/serological status, shift through time and other comorbidities in APS.We included 96 primary APS patients according to the Sydney classification criteria and/or patients with thrombocytopenia and/or autoimmune hemolytic anemia who also fulfilled the serological criteria. We tested aCL, anti-β2GP-I and aPS/PT antibodies and LA. We first registered the MPV and the aforementioned ratios within at least 6 months after an event of thrombosis or thrombocytopenia/AIHA (baseline determination), and during thrombosis/thrombocytopenia/AIHA onset when available (acute event).A lower baseline MPV and a higher PLR characterized the thrombotic group (n = 74). The AUC for baseline PLR was 0.82 (p 0.001): SE of 69%, SP 91%, PPV 96%, NPV 74%, LR+ 13.67 and LR- 0.19. During the acute event, both variables increased. The thrombocytopenic group (n = 66) had a higher baseline MPV and a lower PLR, and during an acute event the PLR decreased more deeply. The AUC for MPV was 0.64 (p = 0.02): SE 44%, SP 92%, PPV 86%, NPV 40%, LR+ 3.3 and LR- 0.85. These findings were not related with the aPL antibody profile status, titers or comorbidities.Basal MPV and PLR might help to identify APS patients according to their thrombotic or thrombocytopenic phenotype. These variables change during the acute events and might be the reflex of physiopathological or compensatory mechanisms in APS.

Introduction Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent thrombosis that can affect the arterial and venous circulation. Objectives To analyze the immunological and pharmacological differences, as well as the clinical outcomes of a cohort of patients with primary antiphospholipid syndrome and secondary antiphospholipid syndrome. Materials and methods A retrospective cohort study was conducted that included 352 records of patients diagnosed with APS and treated between 2014 and 2018. A description is presented of the sociodemographic, clinical, and immunological profile of the population. A bivariate analysis performed using the chi-squared test to determine differences between groups with primary APS and secondary APS, and finally a multivariate analysis to search for associations with thrombotic clinical outcomes in patients with APS. Results The mean age was 42.4 ± 14 years, and 84.6% were females. Two-thirds (67.6%) of the patients had a diagnosis of primary APS, and 32.4% of secondary APS, of which 84% were associated with systemic lupus erythematosus (SLE). Among the thrombotic events, the most frequent were deep vein thrombosis (17.3%) and stroke (9.9%). Obstetric events were frequent, with a prevalence of 39.4% for miscarriages. No differences were found in the sociodemographic or immunoserological profile when comparing the group of primary vs. secondary APS. Thrombotic events were more frequent in the primary APS group, although only pulmonary embolism reached statistical significance. There were no differences between the two groups as regards obstetric events, such as miscarriages. Women were found to be 5 times more likely to have a stroke and 3 times more to have deep vein thrombosis. The anti-B2GPI type IgM increased the probability of presenting miscarriages about 3 times in women with APS. Conclusion The study contains one of the largest Colombian cohorts with APS reported so far, and although it is both clinically and sociodemographically similar to other cohorts, there is a higher prevalence of primary APS. There was a lower frequency of thrombotic complications compared to other cohorts. Patients with primary APS had a tendency to develop thrombosis, as has already been reported in the literature.

Macrophage activation syndrome (MAS) is a serious complication of several rheumatic disorders, among which are the systemic juvenile idiopathic arthritis, Still’s disease and systemic lupus erythematosus. This syndrome is part of the Acquired Haemophagocytic Lymphohistiocytoses, and is a potentially fatal disease, with difficulty in its identification and a lack of consensus regarding its management. A series of cases are described of patients with macrophage activation syndrome, explaining their diagnostic process, their relationship with rheumatic diseases, their monitoring and treatment, as well as the results of different management schemes.

We describe a 64-year-old Caucasian female with a history of Raynaud's disease, hand arthritis, photosensitivity, Sjogren's syndrome and leukocytoclastic vasculitis who presented with progressively worsening fingertip necrosis that began three days after receiving a first dose of Pfizer–BioNTech COVID-19 RNA vaccine. Our workup revealed cryoglobulinemia, hypocomplementemia, elevated antinuclear antibodies (ANA) and IgM antiphospholipid autoantibodies (aPL) directed against phosphatidylserine (aPL-PS), suggesting a diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The patient failed to develop anti-spike IgG antibodies up to two months following vaccination. Disease progression was halted by plasmapheresis, anticoagulation, and immune suppression. We conclude that the vaccine RNA moiety may induce SLE manifesting in APS, cryoglobulinemia, hypocomplementemia, and digital necrosis.

Background The presence of lupus anticoagulant (LA) is an independent risk factor for thrombosis. This laboratory phenomenon is detected as a phospholipid‐dependent prolongation of the clotting time and is caused by autoantibodies against beta2‐glycoprotein I (β2GPI) or prothrombin. How these autoantibodies cause LA is unclear. Objective To elucidate how anti‐β2GPI and anti‐prothrombin antibodies cause the LA phenomenon. Methods The effects of monoclonal anti‐β2GPI and anti‐prothrombin antibodies on coagulation were analyzed in plasma and with purified coagulation factors. Results Detection of LA caused by anti‐β2GPI or anti‐prothrombin antibodies required the presence of the procofactor factor V (FV) in plasma. LA effect disappeared when FV was replaced by activated FV (FVa), both in a model system and in patient plasma, although differences between anti‐β2GPI and anti‐prothrombin antibodies were observed. Further exploration of the effects of the antibodies on coagulation showed that the anti‐β2GPI antibody attenuated FV activation by activated faxtor X (FXa), whereas the anti‐prothrombin antibody did not. Binding studies showed that β2GPI‐‐antibody complexes directly interacted with FV with high affinity. Anti‐prothrombin complexes caused the LA phenomenon through competition for phospholipid binding sites with coagulation factors as reduced FXa binding to lipospheres was observed with flow cytometry in the presence of these antibodies. Conclusion Anti‐β2GPI and anti‐prothrombin antibodies cause LA through different mechanisms of action: While anti‐β2GPI antibodies interfere with FV activation by FXa through a direct interaction with FV, anti‐prothrombin antibodies compete with FXa for phospholipid binding sites. These data provide leads for understanding the paradoxical association between thrombosis and a prolonged clotting time in the antiphospholipid syndrome.

Objective Most high-risk thrombotic antiphospholipid syndrome (APS) patients test positive for anti-β2-glycoprotein I (aβ2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Information on the influence of these antibodies on thrombin generation and activated protein C resistance (aPCr) is still sparse and contradictory. Methods Plasma of 16 patients poured into a β2GPI affinity column allowed the perfect separation of aβ2GPI and aPS/PT antibodies. aPS/PT antibodies were further purified through a prothrombin affinity column. Obtained material was spiked into normal pooled plasma (NPP) and tested in the thrombin generation assay in the absence or presence of aPC. Results aPS/PT antibodies showed a marked anticoagulant effect. Affinity purified aPS/PT and aβ2GPI antibodies from five patients were compared. aPS/PT antibodies showed significantly prolonged lag time and time to peak (5.0 minutes [interquartile range (IQR)3.5-6.1] versus 2.7 minutes [IQR2.2-3.5], P = .03 and 8.7 minutes [IQR6.7-10.3] versus 5.7 minutes [IQR4.5-6.2], P = .05, respectively) and significantly lower peak and velocity index (143 nmol/L [IQR131-163] versus 171 nmol/L [IQR157-182], P = .03 and 35 nmol/L/min [IQR32-59] versus 72 nmol/L/min [IQR54-77], P = .03, respectively). When aPC was added to the system, aPCr was significantly increased compared to controls for both aβ2GPI and aPS/PT antibodies. However, it was significantly stronger using aPS/PT antibodies. Median inhibition of endogenous thrombin potential was 22% (IQR16-33) with aPS/PT compared to 52% (IQR46-56) with aβ2GPI antibodies (P = .002). Conclusions Aβ2GPI antibodies show a mild anticoagulant and moderate procoagulant effect in thrombin generation and moderate aPC resistance. Conversely, aPS/PT antibodies show a strong anticoagulant effect and a strong aPCr.

Resume Introduction L’endocardite de Libman-Sacks est une complication rare du syndrome des antiphospholipides. L’anticoagulation par anti-vitamine K est le traitement de reference, parfois associee a une chirurgie. Dans les dernieres recommandations EULAR, l’utilisation des anticoagulants oraux directs est deconseillee pour la prise en charge du syndrome des antiphospholipides, en particulier en cas de profil a haut risque. Observation Nous rapportons le cas d’une patiente de 63 ans atteinte de sclerose en plaque et d’un syndrome des antiphospholipides ayant presente une endocardite mitrale de Libman-Sacks compliquee d’accidents vasculaires ischemiques apres deux annees d’apixaban. La reintroduction de tinzaparine puis de warfarine au long cours et deux mois d’hydroxychloroquine ont permis une amelioration des lesions valvulaires. Conclusion A notre connaissance, il s’agit du premier cas d’endocardite de Libman-Sacks survenue sous apixaban pour le traitement d’un syndrome des antiphospholipides. Cette atteinte grave conforte l’idee que les anticoagulants oraux directs ne sont pas a utiliser dans la prevention des evenements thrombotiques au cours du syndrome des antiphospholipides.

Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disorder characterized by the presence of antiphospholipid antibodies as well as an increased frequency of venous or arterial thrombosis and/or obstetrical morbidity. The spectrum of disease varies from asymptomatic to a severe form characterized by widespread thrombosis and multiorgan failure, termed catastrophic APS (CAPS). CAPS affects only about ~1% of APS patients, often presents as a thrombotic microangiopathy and has a fulminant course with >40% mortality, despite the best available therapy. Animal models have implicated complement in the pathophysiology of thrombosis in APS, with more recent data from human studies confirming the interaction between the coagulation and complement pathways. Activation of the complement cascade via antiphospholipid antibodies can cause cellular injury and promote coagulation via multiple mechanisms. Finally, analogous to classic complement-mediated diseases such as atypical hemolytic uremic syndrome, a subset of patients with APS may be at increased risk for development of CAPS because of the presence of germline variants in genes crucial for complement regulation. Together, these data make complement inhibition an attractive and potentially lifesaving therapy to mitigate morbidity and mortality in severe thrombotic APS and CAPS.

Objective: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. Methods: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. Results: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. Conclusions: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy. Objetivo: Las sociedades españolas de ginecología y obstetricia, de medicina interna y de reumatología han constituido un grupo de trabajo paritario para la elaboración de 3 documentos de consenso sobre el control del embarazo en mujeres con lupus eritematoso sistémico (LES) y síndrome antifosfolípido (SAF).Métodos: Cada una de las sociedades científicas implicadas propuso 5 representantes en base a su experiencia en el área del control del embarazo en pacientes con enfermedades autoinmunes. Las recomendaciones se elaboraron siguiendo la metodología Delphi. Resultados: En este segundo documento se incluyen las recomendaciones que abordan el manejo del embarazo normal y sus complicaciones en mujeres con LES/SAF. Se presentan las recomendaciones relacionadas con el seguimiento del embarazo, la actividad lúpica, el bloqueo cardíaco congénito, las manifestaciones trombóticas y obstétricas del SAF y los defectos de placentación. Conclusiones: Estas recomendaciones multidisciplinares se consideran herramientas en la toma de decisiones para los clínicos involucrados en la asistencia a pacientes con LES/SAF durante el embarazo.

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.

Objective Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialised assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. Methods The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. Results 161 recommendations were prepared that address the three periods indicated. This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. Conclusions These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Introduction Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), particularly those carrying the JAK2V617F mutation, are at increased risk of thrombosis. While an association of MPNs with autoimmune disorders has been established, the prevalence of inherited or acquired thrombophilias in JAK2V617F-positive patients remains obscure. We therefore investigated the coincidence of the JAK2V617F mutation with additional thrombogenic risk factors. Methods In a retrospective study, we analyzed all patients referred for thrombophilia work-up between 01/2011 and 08/2019, in whom additional JAK2V617F mutation analysis was performed because of thromboembolic events that were recurrent, atypically located and/or associated with abnormal blood counts. Results Of 472 tested patients, 49 (10.4%) were JAK2V617F-positive. While the frequency of inherited thrombophilias (factor V Leiden and prothrombin G20210A mutation, deficiency of antithrombin, protein C, protein S) was not different between the two groups, the prevalence of definite antiphospholipid syndrome (APS), mostly associated with a moderate- or high-risk antibody profile, was significantly higher in patients with (22.4%) than in those without (8.4%) JAK2V617F mutation (p Conclusion We found a significant association between JAK2V617F-positive MPN and definite APS. The presence of concomitant APS in patients carrying the JAK2V617F mutation may lead to earlier manifestation of thromboembolic events and may warrant more aggressive antithrombotic treatment strategies to prevent recurrence.

Aim To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD). Data sources EMBASE and MEDLINE databases were searched from inception to March 2020 for clinical studies reporting on the association between of aPL [IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA)] and PAD. Methods We determined the pooled prevalence (PP) of patients positive for aPL in PAD or the PP of PAD in patients positive for aPL; we employed Peto's odds ratio with random effect for the meta-analysis. Results Twenty-one studies comprising 6,057 patients were evaluated: in patients with PAD, the PP of IgG aCL was 12% vs 4.1% in those without, IgM aCL was 13.2% vs 2.1%, and LA 13.3% vs 3.3%, respectively. The PP of patients with LA was greater in critical limb ischemia than in the control group (19.3% vs 4.2%). Also, the PP of patients with LA was greater in the failed than in the successful revascularisation group (35.8% vs 15.8%). The PP of post-procedural revascularisation failures was similar in the groups given or not given oral anticoagulation (59.2% vs 61.9%). Conclusion All the aPL related to PAD regardless of diagnostic definition used, whereas LA related also to critical limb ischaemia and failed revascularisation. Data expressed as percentage of participants positive for aPL limit the interpretation of these relationships.

Autoimmune connective tissue diseases (CTDs) are associated with accelerated atherosclerosis and inflammation, while often requiring immunosuppression. Large-scale outcomes of coronary artery bypass graft (CABG) surgery in this population have not been reported thus far. This study characterized trends in use of CABG in patients with CTDs and the impact of the disease on mortality, in-hospital complications, length of stay, and costs.The 2005 to 2015 National Inpatient Sample was used to identify all adult patients undergoing isolated CABG. The CTDs cohort included rheumatoid arthritis, lupus erythematosus, and antiphospholipid syndrome (APLS), among others. Hierarchical multivariable logistic models were used to calculate the independent impact of CTDs on clinical outcomes and costs.Of an estimated 2,101,591 patients, 41,567 (1.8%) were diagnosed with CTDs (rheumatoid arthritis, 58%; systemic lupus erythematosus, 12%; APLS, 11%) Although the overall annual use of CABG decreased, the proportion of patients with CTDs receiving the operation significantly increased. After adjusting for patient and hospital characteristics, CTDs were not associated with increased mortality (adjusted odds ratio [AOR], 0.91; P = .34) but were protective against cardiovascular (AOR, 0.92; P.003), neurologic (AOR, 0.81; P = .01), and infectious (AOR, 0.80; P = .01) complications. The diagnosis of CTDs was also predictive of reduced length of hospital stay (β-coefficient = -0.40; P.001) and costs (β-coefficient, -$1200; P = .01). On subgroup analysis patients with APLS had significantly increased odds of mortality (AOR, 1.5) and increased renal (AOR, 1.3), infectious (AOR, 1.7), and thromboembolic (AOR, 4.3) complications (all P.05).CABG in patients with CTDs provides acceptable outcomes and paradoxically improved resource use. However CABG in patients with APLS warrants careful consideration given inferior outcomes.

Platelets play such an important role in the process of thrombosis that patients with thrombocytopenia generally have an increased risk of bleeding. However, abnormal thrombotic events can sometimes occur in patients with thrombocytopenia, which is unusual and inexplicable. The treatments for thrombocytopenia and thromboembolism are usually contradictory. This review introduces the mechanisms of thromboembolism in patients with different types of thrombocytopenia and outlines treatment recommendations for the prevention and treatment of thrombosis. According to the cause of thrombocytopenia, this article addresses four etiologies, including inherited thrombocytopenia (Myh9-related disease, ANKRD26-associated thrombocytopenia, Glanzmann thrombasthenia, Bernard-Soulier syndrome), thrombotic microangiopathy (thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, hemolytic uremic syndrome, Hemolysis Elevated Liver enzymes and Low Platelets syndrome, disseminated intravascular coagulation), autoimmune-related thrombocytopenia (immune thrombocytopenic purpura, antiphospholipid syndrome, systemic lupus erythematosus), and acquired thrombocytopenia (Infection-induced thrombocytopenia and drug-induced thrombocytopenia, heparin-induced thrombocytopenia). We hope to provide more evidence for clinical applications and future research.

Background A dilated epidural venous plexus (DEVP) is a rare cause of radiculopathy, back pain, cauda equina syndrome, and other neurological symptoms. This vascular mass can be secondary to inferior vena cava obstruction, portal hypertension, vascular agenesis, and hypercoagulable states. Although rare, DEVP should be considered in the differential diagnosis for patients who present with lumbar radiculopathy. Case Description We present 2 cases involving patients with lumbar DEVP as well as a literature review of the role of hypercoagulability, vascular anatomy, and inferior vena cava thrombosis in the development of DEVP. The first patient had a history of recurrent deep vein thrombosis, systemic lupus erythematosus, and antiphospholipid syndrome. The diagnosis of DEVP was determined after intraoperative biopsy. The patient reported symptom resolution at her 6-month postoperative appointment. The second patient developed DEVP associated with Klippel-Trenaunay syndrome. She presented with back pain and leg weakness, and DEVP was diagnosed via magnetic resonance imaging. A neurosurgeon is currently following the patient. We believe this is the first case of Klippel-Trenaunay syndrome associated with DEVP. Conclusions If a patient presents with an enhancing epidural lesion on magnetic resonance imaging and neurological symptoms, DEVP should be considered in the differential diagnosis. Additionally, a search for inferior vena cava thrombosis should be performed as well as risk factors for venous hypertension and hypercoagulable states.

Lupus anticoagulant (LA) can be a cause of thrombosis and/or pregnancy morbidities, producing antiphospholipid syndrome (APS). An increase in thrombin generation (TG) is correlated with prothrombotic status. Several changes in TG-derived parameters have been reported in APS patients.Evaluate whether the TG phenotype of APS can also be described in LA subjects without clinical manifestations of APS, and to investigate the possible influence of both LA potency and antiphospholipid (aPL) profile on it.TG was analyzed in 153 cases of LA and 41 healthy controls. We have observed prolongation of both lag time (3.7 min vs 2.32 min, p 0.001) and time to peak (6.48 min vs 5.27 min, p 0.001), increased peak height (221.7 nM vs 182.7 nM, p 0.001), slightly higher ETP (221.7 nM·min vs 182.7 nM·min, p = 0.041), and higher velocity index (100.7 nM/min vs 74.53 nM/min, p = 0.001) in LA subjects compared to controls. After adding thrombomodulin (TM), ETP%inh was significantly lower in LA group (37.90% vs 59.90%, p 0.001) showing resistance to TM/activated protein C (APC). Significant differences were found in lag time, time to peak and ETP%inh according to the potency and aPL profile.Previously described differences in TG-derived parameters in APS patients have been confirmed in incidental LA subjects: prolonged lag time and time to peak, slightly higher ETP, higher peak height, and less sensitivity to TM/APC. High LA potency and triple-positive aPL profile enhance differences in lag time, time to peak and, especially, increase APC resistance, but no effect in ETP was observed.

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.

Anticoagulation treatment after a venous thromboembolism event is usually managed on a case-by-case basis. The risk of thrombosis must be weighed against the risk of bleeding. Identifying patients who could benefit from anticoagulation therapy requires the thromboembolism event to be assessed with respect to its presentation and the severity of the triggering factors. A case report is employed to explain the important aspects of practical approaches to venous thromboembolism events after vein surgery. The Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) study has prompted new considerations for anticoagulation management. Patients with antiphospholipid syndrome need to be identified early to lower the risk of thromboembolism also during anticoagulation treatment.