Management Of Antiphospholipid Syndrome Research Articles

Guidelines on the investigation and management of antiphospholipid syndrome.

Guidelines on the investigation and management of antiphospholipid syndrome.

Dilemmas in the diagnosis and management of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is characterized by thrombosis (which may be venous, arterial, or microvascular) and/or pregnancy morbidity in association with persistently positive antiphospholipid antibodies. Although thrombosis and pregnancy morbidity are the main clinical criteria for a diagnosis of APS in the revised Sapporo (Sydney) criteria, recently published American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS have significantly refined the diagnostic algorithm to include a scoring system clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve, and hematologic). Diagnosis of APS is complicated by the fact that significant heterogeneity exists in patients’ clinical presentation, underlying vascular risk factors, and methods of detecting antiphospholipid antibodies. Despite the autoimmune nature of APS, anticoagulation remains the main strategy for secondary prevention of thrombosis. Furthermore, optimal antithrombotic treatment in APS patients with arterial thrombosis remains controversial due to a paucity of data from randomized controlled studies. In this paper, we present 2 cases and highlight the diagnostic and therapeutic challenges they pose and how we approach them in the light of current evidence.

A review on management of antiphospholipid syndrome in clinical practice

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in patients with persistent antiphospholipid antibodies. Thrombotic APS is characterized by venous, arterial, or microvascular thrombosis. The diagnosis is accepted when both one clinical and one laboratory criteria according to the updated Sapporo classification are established. APS may occur in combination with other autoimmune diseases, mainly systemic lupus erythematosus, or in its primary form. Long-term anticoagulation with a vitamin K antagonist is the standard of care for patients who develop thrombosis, considering the high rate of recurrent thrombosis. The current international guidelines are not in favor of recommending direct oral anticoagulants for secondary prevention of thrombotic antiphospholipid syndrome, especially in the context of arterial thrombosis and triple-positive antiphospholipid patients. The most common approach, endorsed by the American College of Chest Physicians guidelines is the combination of heparin and low-dose aspirin (75-100 mg) daily for women who fulfill the clinical and serologic criteria for obstetric APS. New potential therapeutic approaches are under evaluation but actually the anticoagulation remains the cornerstone of treatment.

Antiphospholipid syndrome, thrombosis and multidisciplinary management

Management of antiphospholipid syndrome is unusual for an autoimmune disease in that the mainstay of treatment is not immunosuppression. Here the authors describe some of the thrombotic events that characterise the disease. They also look at diagnosis (again a challenge because there are no diagnostic criteria) and the need for multidisciplinary care.

Controversies in the Management of Antiphospholipid Syndrome.

Strategies to prevent thrombosis in antiphospholipid antibody (aPL)-positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice.

An Update on Antiphospholipid Syndrome.

To review the recent available evidence on epidemiology, pathogenesis, clinical phenotypes, and management of antiphospholipid syndrome (APS) and summarize potential future research perspectives. Accumulating evidence has further expanded our understanding of the disease, including new data about the incidence and prevalence of APS, novel pathways supporting the role of thrombo-inflammation in APS including platelet, monocyte and endothelial cell activation, pro-inflammatory cytokine and chemokine production, complement activation, neutrophil extracellular trap release, and type I interferon gene expression that could yield to new potential treatment targets, better identification of criteria and non-criteria clinical phenotypes, antiphospholipid antibody profiles and their associations with clinical outcomes, prognostic tools, and treatment strategies based on recent evidence-based recommendations for patients with thrombotic and obstetric APS, with or without systemic lupus erythematosus. Ongoing research efforts and international collaborations enhance our knowledge of this rare and often devastating syndrome and help improve patient care and health outcomes.

The Weight of IgA Anti-β2glycoprotein I in the Antiphospholipid Syndrome Pathogenesis: Closing the Gap of Seronegative Antiphospholipid Syndrome

The specific value of IgA Anti-β2glycoprotein I antibodies (aB2GP1) in the diagnosis and management of antiphospholipid syndrome (APS) is still controversial and a matter of active debate. The relevance of the IgA aB2GP1 isotype in the pathophysiology of APS has been increasingly studied in the last years. There is well know that subjects with multiple positive APS tests are at increased risk of thrombosis and/or miscarriage. However, these antibodies are not included in the 2006 APS classification criteria. Since 2010 the task force of the Galveston International Congress on APS recommends testing IgA aB2GP1 isotype in patients with APS clinical criteria in the absence of criteria antibodies. In this review, we summarize the molecular and clinical “state of the art” of the IgA aB2GP in the context of APS. We also discuss some of the characteristics that may help to evaluate the real value of the IgA aB2GP1 determination in basic research and clinical practice. The scientific community should be aware of the importance of clarifying the role of IgA aB2GP1 in the APS diagnosis.

Une endocardite de Libman-Sacks survenant sous apixaban chez une patiente atteinte de SAPL veineux de profil à haut risque

IntroductionLibman-Sacks endocarditis is a rare complication of antiphospholipid syndrome. Anti-vitamin K therapy is the standard treatment, although valvular replacement surgery may be required in some severe cases. In the latest EULAR recommendations, it is advised not to use direct oral anticoagulants in the management of antiphospholipid syndrome, especially of high-risk profile. Case reportWe present a case of a mitral Libman-Sacks endocarditis complicated with multiple strokes occurring in the setting of an antiphospholipid syndrome with triple positive antibody profile in a 63-year-old woman with multiple sclerosis. She was previously treated with apixaban for two years. Tinzaparin followed by prolonged warfarine treatment and two months of hydroxychloroquine resulted in valvular improvement. ConclusionTo our knowledge, this is the first case of Libman-Sacks endocarditis occurring during apixaban therapy in a patient with antiphospholipid syndrome. This severe case highlights the inefficiency of direct oral anticoagulants to prevent thrombotic events in the antiphospholipid syndrome.

New aspects on autoantibodies for classification, diagnosis and therapy within rheumatology

Recent advances in rheumatology indicate increased relevance of autoantibodies. In this regard, positive ANA are now required as entrance criterium for the first EULAR/ACR classification criteria of SLE. Importantly, ANA diagnostic with detection of isolated anti-dense fine speckled antibodies (DSF-70) need consideration since their unique detection has been identified to exclude largely an autoimmune disease. Thus, highly qualified ANA diagnostic preferably on Hep-2 cell lines is a prerequisite of reliable diagnostics.Recent recommendations for the management of antiphospholipid syndrome define high versus low risk seroprofiles which also guide primary and secondary prophylaxis. Importantly triple positive APS patients (positive for anticradiolipin, anti-ß2 GP I positive and carrying lupus anticoagulant) should be treated with vitamin K antagonists while direct oral anticoagulants have been shown to be inferior in terms of risk/benefit. Treatment of obstetric APS is mainly based on low dose aspirin and low molecular heparin. Notably, this treatment should be maintained for 6 weeks after delivery. Thus, serologic findings provide the basis for certain key clinical decisions and require their reliable detection.

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

An update on the management of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent venous or arterial thrombosis with or without pregnancy morbidity in the presence of persistent antiphospholipid (aPL) autoantibodies. Anticoagulation has, until now, formed the cornerstone of treatment but a significant proportion of patients continue to experience thrombosis and pregnancy morbidity despite this treatment. Thrombosis is the most common cause of mortality and accounts for two fifths of deaths. Direct oral anticoagulant drugs represent an attractive alternative to conventional vitamin K antagonist drugs but emerging evidence suggests these may not be suitable for high-risk patients with thrombotic APS. Laboratory studies and case reports of the successful use of different classes of drugs in APS is increasing our understanding of the other pathophysiological mechanisms which may contribute to the high morbidity of APS. This review summarizes current accepted anticoagulant treatment for APS and examines other potential drugs such as immunomodulating agents, statins and novel agents such as sirolimus and defibrotide.

Pregnancy and Systemic Lupus Erythematosus.

As SLE onset is often in young adulthood, pregnancy is common and is usually successful. Pregnancy, though, is considered high-risk due to a combination of maternal (lupus flare, diabetes, pre-eclampsia) and fetal (miscarriage, intrauterine fetal demise, preterm birth, intrauterine growth restriction, congenital heart block) risks. Pregnancy should be planned for a time of good control of SLE (on allowable medications). The antimalarial hydroxychloroquine should be continued. The only permitted immunosuppressive drugs are azathioprine and tacrolimus. Of the antiphospholipid antibodies, only the lupus anticoagulant has been associated with adverse pregnancy outcomes in the largest prospective multicenter study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE). Management of antiphospholipid syndrome in pregnancy is low molecular weight heparin and aspirin, although only 75% of pregnancies are successful.

Management of Antiphospholipid Syndrome in Patients with Systemic Lupus Erythematosus

Purpose of review To provide an approach to primary and secondary prevention of thrombotic events and obstetric complications in patients with antiphospholipid antibodies (aPL) with or without antiphospholipid syndrome (APS), particularly in association with systemic lupus erythematosus (SLE).

Сочетанная тромбофилия по данным гематологического консультирования

Введение. Диагностическая значимость гомозиготной мутации генов факторов свертывания крови FV Leiden и FII, а также их гетерозиготного полиморфизма в сочетании с маркерами первичного антифосфолипидного синдрома как предикторов тромбоза остается неоднозначной. Цель исследования: представить клинические случаи сочетанных тромбофилий, выявленных в процессе амбулаторного гематологического консультирования. Материалы и методы. В базе данных приема гематолога с января 2012 г. по апрель 2017 г. выявлен 891 пациент (837 женщин и 54 мужчины), которым было проведено обследование и консультирование на предмет тромбофилии и/или наличия активных факторов тромбогенного риска. Результаты. Сочетанная тромбофилия выявлена у 7 (0,8%) из 891 обследованного или у 7 (2,8%) из 246 пациентов с факторами тромбогенного риска. В 4 случаях у 2 мужчин (44 и 28 лет) и у 2 женщин (29 и 33 лет) диагноз установлен в связи с тяжелой и/или рецидивирующей венозной и артериальной тромбоэмболией и у 3 женщин (27, 36 и 39 лет) в связи с синдромом потери плода. Заключение. Анализ наблюдений подтверждает целесообразность поиска сочетанной тромбофилии в случае рецидивирующего тромбоза для выбора оптимальной антикоагулянтной терапии. Introduction. The diagnostic signifi cance of homozygous mutation of FV Leiden and FII clotting factor genes, as well as their heterozygous polymorphism in combination with the markers of the primary antiphospholipid syndrome as predictors of thrombosis remains ambiguous. Aim: to present clinical cases of combined thrombophilia revealed during outpatient hematology counseling. Materials and methods. In hematologist database from January 2012 to April 2017 we found 891 patients (837 women and 54 men) who were examined and consulted for thrombophilia and/or presence of active factors of thrombogenic risk. Results. Combined thrombophilia was identifi ed in 7 (0.8%) of 891 patients or in 7 (2.8%) of 246 patients with thrombogenic risk factors. In 4 cases — 2 men (44 and 28 years) and 2 women (29 and 33 years old) had a diagnosis due to severe and/or recurrent venous and arterial thromboembolism and 3 women (27, 36 and 39 years) had a diagnosis due to fetal loss syndrome. Conclusion. The observations confi rm the practicability of researching for combined thrombophilia in case of recurrent thrombosis for the choice of optimal anticoagulant therapy.

Management of antiphospholipid syndrome

Antiphospholipid syndrome, also known as ‘Hughes Syndrome’, is an autoimmune disease characterised by a set of clinical manifestations, almost all of which are direct or indirect sequelae of a hypercoagulable...

Challenges in the diagnosis and management of anti-phospholipid syndrome: a case from Cameroon

BackgroundAnti-phospholipid syndrome (APLS) is a condition characterized by the presence of raised plasma levels of anti-phospholipid antibodies associated with thrombo-embolic disease and/or poor obstetrical outcomes in women. The epidemiology of APLS is unknown in most sub-Saharan African countries due to limited access to diagnosis tools.Case summaryWe report the case of APLS in a 29-year-old obese woman that was preceded by pre-eclampsia and fetal death. The diagnosis of APLS was made during a thrombo-embolic episode 4 years after the poor obstetrical outcome. Her management was challenging, as she had three thrombo-embolic events within 18-months despite treatment with anti-coagulant (acenocoumarol).ConclusionThis case highlights the need for screening for APLS after an episode of hypertensive disease in pregnancy or fetal death, and the challenges faced with the treatment, such as resistance to antivitamin K anti-coagulants and the desire for maternity.

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-β2-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.

Recognition and management of antiphospholipid syndrome.

This article summarizes the recent developments in the recognition and management of antiphospholipid syndrome (APS). Five Task Forces, created as part of the 14th International Congress on antiphospholipid antibodies (aPL), published their systematic reviews. 'For the recognition of APS': the assessment of aPL profile is crucial for risk stratification; lupus anticoagulant positivity, especially in the context of 'triple aPL positivity' displays the highest risk; a panel of criteria and noncriteria aPL tests may help better risk-stratify the aPL-positive in the future. 'For the management of APS': direct oral anticoagulants are not currently recommended; statins ameliorate the proinflammator/thrombotic markers, whereas hydroxychloroquine reduces the risk of thrombosis in experimental models and lupus patients, which justify their use as an adjunctive treatment in refractory cases; B-cell inhibition may have a role in difficult-to-treat patients with hematologic and microthrombotic/angiopathic manifestations; and complement and mammalian targets of rapamycin complex pathway inhibition are promising targets in APS. Warfarin, heparin, and/or antiplatelet drugs are the standard of care for aPL-positive patients. Recent studies suggest novel approaches that target new coagulation and immunomodulatory pathways; mechanistic and/or controlled clinical studies are needed to determine the effectiveness of these novel approaches.

Rheumatologic emergencies.

Rheumatological conditions can sometimes present as emergencies. These can occur due to the disease process or infection; contrary to what many people think, rheumatologic emergencies like a pain, rheumatic crisis, or attack gout do not compromise the patient's life. This article mentioned only true emergencies: catastrophic antiphospholipid syndrome (cAPS), kidney-lung syndrome, central nervous system (CNS) vasculitis, anti-Ro syndrome (neonatal lupus), and macrophage activation syndrome (MAS). The management of above emergencies includes critical care, immunosuppression when indicated, and use of a diagnostic flowchart as well as fast laboratory profile for making decisions. Anticoagulants have to be used in the management of antiphospholipid syndrome. A good understanding of these conditions is of paramount importance for proper management.

Obstetrical Considerations and Management of Antiphospholipid Syndrome

Antiphospholipid syndrome is a pro-thrombotic, pro-inflammatory condition defined by at least one clinical criterion and one laboratory finding. Clinical criteria are met by history of thrombosis or obstetric morbidity, including recurrent early pregnancy loss, fetal death, or delivery prior to 34 weeks gestation due to pre-eclampsia or placental insufficiency. Laboratory criteria are evidence of lupus anticoagulant or high titers of anticardiolipin or anti-β2-glycoprotein-I IgG or IgM. Treatment during pregnancy is primarily based on anticoagulant therapy, either at prophylactic or therapeutic doses depending on thrombosis history. This treatment certainly reduces thrombosis risk and may also improve obstetric outcome.