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Lupus anticoagulant (LA) is a well-established risk factor for the clinical manifestations of antiphospholipid syndrome (APS). Accurate LA detection is an essential prerequisite for optimal diagnosis and management of patients with APS or aPL carriers. Variability remains a challenge in LA testing, with reliable detection influenced by multiple factors, including pre-analytical conditions, anticoagulation treatment, choice of tests and procedures performed, as well as interpretation of results, that can lead to false-positives or negatives. A standardised approach to LA testing, following current guidance, based on published data and international consensus, and with attention to detail, is required to underpin accurate detection of LA. Future work should focus on better characterisation of the nature of LA, which may ultimately lead to improved diagnosis and management of patients with APS and aPL carriers. This article reviews current practice and challenges, providing an overview on detection of LA. [ABSTRACT FROM AUTHOR]

Catastrophic antiphospholipid syndrome (CAPS) is a rare life threatening presentation of antiphospholipid syndrome. Surgery has been proposed as one of the triggering factors for this life threatening entity. There are no detailed published reports in the current literature describing CAPS as a complication after surgery. We report a case of a 21 year old that developed CAPS postoperatively and discuss the multidisciplinary approach for diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective We aimed to analyse the prevalence of non-criteria anti-phospholipid (aPL) antibodies and their role in the diagnosis, treatment and prognosis in a cohort of patients with clinical features consistent with a diagnosis of antiphospholipid syndrome (APS), but persistently negative for criteria aPL – anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2-GPI) and lupus anticoagulant (LA) – named seronegative APS (SN-APS). Methods Sera from SN-APS patients were tested for aCL by TLC-immunostaining, anti-vimentin/cardiolipin (aVim/CL) and anti-phosphatidylserine/prothrombin (anti-PS/PT) by ELISA. Control groups of our study were APS patients and healthy controls. Results We enrolled 114 consecutive SN-APS patients, 69 (60.5%) resulted positive for at least one non-criteria test in two occasions 12 weeks apart. Among the persistently positive patients to these tests, 97% resulted positive for aCL by TLC-immunostaining, 52.3% for aVim/CL and 17.4% for aPS/PT. SN-APS patients with double positivity (aCL by TLC-immunostaining and aVim/CL) showed a likelihood positive ratio of 8 to present mixed thrombotic and obstetrical features. Among SN-APS patients tested positive, after the therapeutic changes, three cases of recurrent thrombosis were observed [median follow-up 41 months (IQR 39.5)]. Twenty pregnancies were recorded in 17 SN-APS patients after the detection of unconventional aPL and 12 of them (60%) experienced a good outcome under conventional treatment for APS. Conclusions This is the largest monocentric study demonstrating that aCL tested by TLC-immunostaining and aVim/CL can detect aPL positivity in SN-APS. It may encourage clinicians to monitor and provide adequate targeted therapy, which improve SN-APS prognosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 50-year-old man with antiphospholipid syndrome (APS) presents to your office for the first time with a 3-month history of worsening dyspnea, dry cough, and early morning blood-tinged sputum. Topics include the APS diagnosis was based on an unprovoked left leg deep vein thrombosis, and the physical examination is normal except for livedo racemosa around his knees.

Objectives: We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years. Methods: Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF. Results: Neither patient had recurrent microthrombotic disease during a 4-year follow-up. Conclusions: As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APLS) is characterised by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies. Catastrophic Antiphospholipid Syndrome (CAPS) is a severe and rare form of antiphospholipid syndrome characterised by multiple site thrombosis involving small, medium and large blood vessels occurring over a short period of time (usually 1 week) causing multiorgan failure. We present an unusual case of left upper limb acute arterial thrombosis with purpura fulminans like skin lesions precipitated by swine flu (H1N1) infection with adult respiratory distress syndrome subsequently developing acute renal failure, retinal infarcts, multiple acute cerebral infarcts, cardiac valvular vegetations and hemolytic anemia with recurrent bleeding episodes. A positive lupus anticoagulant confirmed the diagnosis of CAPS. In spite of early initiation of triple therapy (anticoagulation, high dose steroids, plasmapheresis) our patient did not survive. This rare case of probable CAPS is presented with an aim to study the clinical manifestations, laboratory findings, efficacy of therapy and prognosis in the medical ICU. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases. Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 years ± 9.9 SD). Triple aPL positivity (IgG/IgM anticardiolipin + IgG/IgM anti-β2Glycoprotein I + lupus anticoagulants) significantly prevailed in the CAPS patients with respect to the controls (p = 0.003). IgG anticardiolipin and IgG anti-β2Glycoprotein I mean antibody titers of the CAPS patients were significantly higher than those of the controls (p = 0.0018 and p = 0.003, respectively). Triple therapy (anticoagulation + plasma exchange + steroids) was administered to all the CAPS cases except for one. Beginning in 2009, intravenous immunoglobulin infusion has also been included in the triple therapy protocol (six patients). All the patients recovered from CAPS; five showed renal failure and one a I-II class New York Heart Association (NYHA) dilated cardiomyopathy. Long-term outcomes of CAPS included a gradual worsening of renal failure in one patient who required hemodialysis 30 years after the acute episode. Renal function improved in the other four patients. The patient affected with dilated cardiomyopathy worsened to a II class NYHA over a five year period. Currently all the patients are alive. A specific antiphospholipid antibody profile could be considered a risk factor associated to CAPS. Early use of a defined treatment protocol based on triple therapy either or not associated with IVIG was associated with recovery in all CAPS patients. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS) is a condition characterized by the occurrence of thromboembolic events and/or pregnancy loss combined with one laboratory criterion among Lupus Anticoagulant- LAC, anticardiolipin –aCL, and anti β2-Glycoprotein I -aβ2GPI antibodies. Several hypotheses were put forward to explain the causal role of antibodies in the clinical events but none is fully convincing. Current laboratory diagnosis is based on three tests (LAC, IgG/IgM aβ2GPI and IgG/IgM aCL antibodies). The triple-positive profile (all the three tests positive, same isotype) is associated with a higher risk for thrombosis. The mainstay of therapy in thrombotic APS is anticoagulation, with VKAs being the cornerstone. Low dose aspirin in combination or alone may have a role in arterial thrombosis, and in primary thromboprophylaxis. The Non-Vitamin K Antagonists Oral Anticoagulants (NOACs) role in the therapy of APS is under investigation but not verified. Alternative treatment options including rituximab and eculizumab have been successfully reported in few cases of catastrophic APS. [ABSTRACT FROM AUTHOR]

The catastrophic antiphospholipid syndrome (CAPS) is a life-threating variant of the antiphospholipid syndrome characterized by the development of multiple thrombosis in a short period of time, usually ending up in the failure of function of several vital organs. Most CAPS episodes are related to a prothrombotic situation or precipitating factor such as infections, surgical procedures or malignant diseases. In patients with CAPS, the development of multiple thrombosis leads to an important cytokine release that worsens the already critical patient's situation. The disease usually involves the kidneys, the lungs and the heart, although any organ system can be affected. Although occasionally the disease affects large vessels, in the majority of cases it affects small vessels, leading to a disseminated microangiopathic syndrome resembling thrombotic thrombocytopenic purpura. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in those CAPS cases associated to systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Mortality is still around 30% despite current treatment. [ABSTRACT FROM AUTHOR]

Objective: To elucidate clinical feature and anti-phospholipid antibody (aPL) profiles, including lupus anticoagulant (LA), anti-cardiolipin (CL) antibodies and anti-phosphatidylserine/prothrombin (PS/PT) antibodies, of pregnancy failure in patients with antiphospholipid antibody syndrome (APS) already treated with conventional therapy. Materials and methods: Thirty-four women with a history of pregnancy who were diagnosed with APS between 2008 and 2016 were included in the study. We defined the successful pregnancy group as women who gave birth to a healthy baby over 1500 g after 34 weeks of pregnancy under conventional treatment (heparin and/or low-dose aspirin). The unsuccessful pregnancy group was defined as women whose pregnancy outcomes did not meet the aforementioned criteria despite the conventional therapy. The clinical features and aPL profiles were compared between the two groups. Results: Fifteen women were classified into the unsuccessful pregnancy group; seven women were in the successful pregnancy group. Having history of both thrombosis and pregnancy morbidity and LA positivity were significantly more prevalent in the unsuccessful pregnancy group than in the successful pregnancy group (p <.05, respectively). In contrast, single positivity of anti-CL antibody was negatively associated with APS-associated pregnancy morbidity under the conventional treatment (p <.01). The proportion of anti-PS/PT IgG-positive patients was significantly higher in the unsuccessful pregnancy group (p = .02, OR 18.7, 95% CI 1.50, 232.29) with high concordance rate with LA (97% consistence). Conclusion: History of both thrombosis and pregnancy morbidity and the positivity of LA and/or anti-PS/PT-IgG, not but anti-CL-antibodies were correlated with APS-associated pregnancy morbidity refractory to conventional treatment. Clinical feature and aPL profiles might help us to make risk assessment for adverse pregnancy outcomes in patients with APS. [ABSTRACT FROM AUTHOR]

Objectives. The objective of this study was to assess the effect that triple therapy (anticoagulation plus CS plus plasma exchange and/or IVIGs) has on the mortality risk of patients with catastrophic APS (CAPS) included in the CAPS Registry. Methods. Patients from the CAPS Registry were grouped based on their treatments: triple therapy; drugs included in the triple therapy but in different combinations; and none of the treatments included in the triple therapy. The primary endpoint was all-cause mortality. Multivariate logistic regression models were used to compare mortality risk between groups. Results. The CAPS Registry cohort included 525 episodes of CAPS accounting for 502 patients. After excluding 54 episodes (10.3%), a total of 471 patients with CAPS were included [mean (S.D.) age 38.5 years (17); 68.2% female; primary APS patients 62%]. Overall, 174 (36.9%) patients died. Triple therapy was prescribed in 189 episodes (40.1%), other combinations in 270 (57.3%) and none of those treatments in 12 episodes (2.5%); the mortality rate in the three groups was 28.6, 41.1 and 75%, respectively. Triple therapy was positively associated with a higher chance of survival when compared with non-treatment [adjusted odds ratio (OR) = 9.7, 95% CI: 2.3, 40.6] or treatment with other combinations of drugs included in the triple therapy (adjusted OR = 1.7, 95% CI: 1.2, 2.6). No statistical differences were found between patients that received triple therapy with plasma exchange or IVIGs (P = 0.92). Conclusion. Triple therapy is independently associated with a higher survival rate among patients with CAPS. [ABSTRACT FROM AUTHOR]

Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mainstay of the treatment of obstetric APS, allowing a birth rate in 70% of cases. The management of refractory APS, thrombotic as well as obstetric, is highly debated, but an increasing burden of evidence points towards the beneficial effects of multiple treatments. Similarly, a management envisaging multiple drugs (anticoagulation, steroids, plasma exchange and/or intravenous immunoglobulins) is the most effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher risk of thrombotic and obstetric complications compared to the general population, thus potentially benefitting of a pharmacological intervention. LDASA and hydroxychloroquine can be considered as options, in particular in case of high risk aPL profile, concomitant cardiovascular risk factors or associated autoimmune disease. APS is apparently a simple condition, but its multifaceted nature requires a complex and tailored treatment. [ABSTRACT FROM AUTHOR]

The major treatment issues in Antiphospholipid Syndrome (APS) include the the prevention of first thrombosis, the treatment of acute thromboembolic manifestations, the choice of anticoagulation, the duration of anticoagulation and secondary thrombosis prevention. Anticoagulation should individualized to the patient and clinical setting. Clasical anti vitamin K antagonists, warfarin and acenocumoral, carry some risks and disadvantages. Direct thrombin inhibitor and direct anti-Xa inhibitors are currently available and were approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and for the prevention of recurrent DVT and pulmonary embolism. Besides many case series reports, there are ongoing clinical trials testing their efficiency and safety in patients with APS. In this paper we reviewed the advantages, risks and disadvantages for the use of direct oral anticoagulants in this category of patients. [ABSTRACT FROM AUTHOR]

The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion). We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed. To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted. [ABSTRACT FROM AUTHOR]

Background: The antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined. Objective: To test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up. Methods: 244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL. Results: During the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p<0.001). The incidence rate of APS-events was 3.1% per year in IgA-aB2GP1 positive patients and 0.6% per year in the control group. Arterial thrombosis were the most frequent APS-events (N = 25, 55%) and were mainly observed in Group-1 patients (21 vs 4, p = 0.001). Multivariate analysis were shown as independent risk-factors for the development of APS-events, age, sex (men) and presence of IgA-aB2GP1 (odds ratio 5.25, 95% CI 2.24 to 12.32). Conclusion: The presence of IgA-aB2GP1 in people with no history of APS-events is the main independent risk factor for the development of these types of events, mainly arterial thrombosis. [ABSTRACT FROM AUTHOR]

Introduction Antiphospholipid syndrome (APS) is a common acquired thrombophilia associated with a high thrombotic risk, in which vitamin K antagonists (VKA) represent the mainstay of therapy. Case series involving up to 35 patients with APS suggested limited efficacy and safety of direct oral anticoagulants (DOACs). Material and methods In the prospective case series we followed 56 consecutive patients with APS (44 women and 12 men, aged from 22 to 64 years), including 33 (60%) associated with systemic lupus erythematosus (SLE) and 16 (28.6%) with triple APS who were treated with DOACs due to their preferences or unstable anticoagulation with VKA. DOACs were started at least 3 months since the thromboembolic event in patients with D-dimer below 500 ng/ml. Results Forty-nine (87.5%) patients were treated with rivaroxaban, 4 (7.3%) with dabigatran and 3 (5.4%) with apixaban. During follow-up of 2 to 43 (mean 22) months, 6 (10.7%, 5.8 per 100 patient-years) patients (4 women and 2 men, 4 with triple positive APS) experienced recurrent thrombosis, including deep vein thrombosis ( n = 4, including 2 episodes preceded by nonadherence), superficial vein thrombosis ( n = 1) and non-ST elevation myocardial infarction ( n = 1). The recurrence rate of VTE on DOACs was 5.8 per 100 patient-years. Two patients (3.6%) experienced severe bleeding. Conclusions This case-series suggests that DOACs are safe in patients with APS. These findings need to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Background: Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA.Methods: We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs).Results: During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22).Conclusions: Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by recurrent thromboses and fetal losses with the presence of antiphospholipid antibodies. The main treatment to prevent recurrent thrombotic events is oral anticoagulation with vitamin K antagonist (VKA), which requires frequent monitoring and dosage adjustments. Outpatient anticoagulation monitoring has its limitations, such as patients spending long hours between the testing procedure and waiting for the results to be adjusted. To optimize this adjustment and to improve APS patients-doctors relationship, we developed a website to help monitor APS patients, called Antiphospholipid Syndrome On Cloud or APSOnCloud. To test it, since March 2014 to March 2016, we registered 20 patients with APS that have inserted 132 international normalized ratio (INR) values. Sixty two percent were out of range and it took on average 7 hours for the doctor in charge to adjust these values. The mean time in therapeutic range was 58.1%. Our preliminary experience in monitoring VKA oral anticoagulation on APSOnCloud suggests that patients with APS might benefit from this web-based monitoring. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis and pregnancy morbidity in the presence of pathogenic autoantibodies known as antiphospholipid antibodies (aPL). APS may be associated with other diseases, mainly systemic lupus erythematosus (SLE). The presence or absence of SLE might modify the clinical or serological expression of APS. Apart from the classical manifestations, APS patients with associated SLE more frequently display a clinical profile with arthralgias, arthritis, autoimmune hemolytic anemia, livedo reticularis, epilepsy, glomerular thrombosis, and myocardial infarction. The management of patients with SLE and APS/aPL should include an accurate stratification of vascular risk factors. Low dose aspirin and hydroxychloroquine should be considered as primary prophylaxis. In high risk situations, such as surgery, prolonged immobilization, and puerperium, the prophylaxis should be potentiated with low molecular weight heparin. The challenge of treating patients with a previous vascular event (secondary prophylaxis) is the choice of treatment (anti-platelet agents, anticoagulation with vitamin K antagonists or combined therapy) and its duration, based on individual risk stratification and the site of vascular presentation. The role of novel anticoagulants in APS patients is still to be clearly defined. Novel approaches are needed since the prognosis of SLE patients with APS/aPL is still worse than that of SLE patients with negative aPL. The goal for the future is to improve the outcome of these patients by means of early recognition and optimal preventative treatment. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis or pregnancy loss with persistent positive antibodies. Standard treatment for APS with history of thromboembolism is heparin or low-molecular-weight heparin followed by a vitamin K antagonist (VKA). Novel oral anticoagulants (NOACs) could be effective in patients with APS, but none carry indications for treatment related to APS. Clinical Evidence: Five case reports or series with rivaroxaban and dabigatran suggest thrombotic events occur most often in the higher risk population (arterial thrombosis and/or triple positive antibodies) or in patients who had recurrent VTEs on warfarin therapy. An observational cohort in 26 APS patients using dabigatran or rivaroxaban described a recurrent thrombotic event in only 1 patient after 8 months of treatment. The event-free survival rate was 87.9% at 12 months. Three controlled clinical trials are underway to evaluate the thrombotic risk of NOACs (RAPS, TRAPS, and ASTRO-APS). Discussion: There are no completed studies that evaluate the use of NOACs in APS compared to VKAs. One major disadvantage of the NOACs is the limited availability of reversal agents for patients with a major bleeding episode. An increased risk of thrombotic events is associated with arterial occlusions and triple antibody positivity APS with both warfarin and NOACs; this is currently being researched in the TRAPS study. Conclusion: Based on current available evidence, VKAs remain the standard of care in the treatment of APS. Results of ongoing trials may offer more guidance on how to appropriately use NOACs for patients with APS. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (apL). Management of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thrombo-prophylaxis is recommended in patients with systemic lupus erythromatosus (SLE) and obstetric APS. Obstetric APS care is based on high-risk management and treatment with aspirin and heparin. Possible future therapies include statins, hydroxychloroquine, rituximab, and new anticoagulant drugs. Current research is focused on targeting components of the complement system, interfering with aPL–mediated cell activation and using tailored peptides to block the pathogenic subpopulation of aPL. [ABSTRACT FROM PUBLISHER]

In the antiphospholipid syndrome (APS), patients produce antiphospholipid antibodies (aPL) that promote thrombosis and adverse pregnancy outcomes. Current therapy with anticoagulation is only partially effective and associated with multiple complications. We previously discovered that aPL recognition of cell surface β2-glycoprotein I (β2-GPI) initiates apolipoprotein E receptor 2 (apoER2)-dependent signaling in endothelial cells and in placental trophoblasts that ultimately promotes thrombosis and fetal loss, respectively. Here we sought to identify a monoclonal antibody (mAb) to β2-GPI that negates aPL-induced processes in cell culture and APS disease endpoints in mice. In a screen measuring endothelial NO synthase (eNOS) activity in cultured endothelial cells, we found that whereas aPL inhibit eNOS, the mAb 1N11 does not, and instead 1N11 prevents aPL action. Coimmunoprecipitation studies revealed that 1N11 decreases pathogenic antibody binding to β2-GPI, and it blocks aPL-induced complex formation between β2-GPI and apoER2. 1N11 also prevents aPL antagonism of endothelial cell migration, and in mice it reverses the impairment in reendothelialization caused by aPL, which underlies the non-thrombotic vascular occlusion provoked by disease-causing antibodies. In addition, aPL inhibition of trophoblast proliferation and migration is negated by 1N11, and the more than 6-fold increase in fetal resorption caused by aPL in pregnant mice is prevented by 1N11. Furthermore, the promotion of thrombosis by aPL is negated by 1N11. Thus, 1N11 has been identified as an mAb that attenuates APS-related pregnancy complications and thrombosis in mice. 1N11 may provide an efficacious, mechanism-based therapy to combat the often devastating conditions suffered by APS patients. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs). Patients and methods Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed. Results The mean age was 45 ± 14.36 (range 27–69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17–153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2–36 months). There was no recurrence of thrombosis by the time of data collection. Conclusions Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients. [ABSTRACT FROM AUTHOR]

Background Patients with antiphospholipid syndrome (APS) often have thrombotic recurrences, sometimes despite appropriate ongoing anticoagulant treatment. Identifying APS vascular patients at high risk for thrombotic recurrences is still an unsolved issue. Objectives To report the real-life experience of thrombotic recurrences in APS patients included in the Piedmont observational cohort study, and evaluate clinical and laboratory risk factors for thrombotic recurrences. Patients A multi-centre observational study was performed by enrolling 177 patients with vascular APS (primary APS in 99 subjects (56%)); the median follow-up was five years (range 1–26 years). Results The observed thrombotic recurrence rate was about 7.5/100 patient years in the first five years after the first thrombotic event. While the first recurrence often occurred (45%) in patients who were not on oral anticoagulant therapy (OAT), the second recurrence mainly occurred despite ongoing OAT (80%). However, due to the real-life observational nature of this study, treatment was based on the treating physician’s judgement, and no structured therapeutic protocol was applied. Moreover, compliance with OAT was not available. No differences in antiphospholipid antibodies (aPL) profile were observed between patients with or without thrombotic recurrences, but a high risk aPL profile (Miyakis type 1 and 2a) was present in 96% of our patients, 26% of whom had triple positivity. Diabetes (p < 0.01, OR 10), inherited thrombophilia (p < 0.0078, OR 4) and OAT withdrawal were independent risk factors for recurrences. Conclusions With the limit of a real-life observational cohort study, the thrombotic recurrence rate in APS was as high as 7.5/100 patient years in the first five years after the first thrombotic event. OAT discontinuation, diabetes and inherited thrombophilia, when associated with a high-risk aPL profile, are risk factors for thrombotic recurrences. [ABSTRACT FROM AUTHOR]

The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as unpredictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been speculated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention during rivaroxaban use. All patients had venous thrombosis as the initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS. [ABSTRACT FROM AUTHOR]

Catastrophic antiphospholipid syndrome is a rare condition with high morbidity and mortality. We present a refractory case of catastrophic antiphospholipid syndrome with a view to highlight the importance of early identification and aggressive treatment of this condition. A 36-year-old female presented with clinical manifestations of multiorgan vascular occlusion with a known history of primary antiphospholipid syndrome. The presentation was on a background of a recent change of her long-term anticoagulation from warfarin to therapeutic low-molecular-weight heparin. Given that multiorgan involvement with 3 organ systems occurred nearly simultaneously, a diagnosis of probable catastrophic antiphospholipid syndrome was made. Prompt therapeutic anticoagulation, antiplatelet, and glucocorticoid therapy was commenced. Despite this, the patient continued to demonstrate clinical features concerning for ongoing small vessel occlusion necessitating aggressive immunomodulatory therapy in the form of intravenous immunoglobulin, plasma exchange, and rituximab. [ABSTRACT FROM AUTHOR]

For patients with antiphospholipid syndrome (APS), the consensus is to treat those who develop thrombosis with long-term oral anticoagulation therapy and to prevent obstetric manifestations by use of aspirin and heparin. These recommendations are based on data from randomized controlled trials and observational studies. Despite this body of knowledge, areas of uncertainty regarding the management of APS exist where evidence is scarce or nonexistent. In other words, for a subset of patients the course of management is unclear. Some examples are patients with 'seronegative' APS, those who do not fulfil the formal (clinical or serological) classification criteria for definite APS, and those with recurrent thrombotic events despite optimal anticoagulation. Other challenges include the treatment of clinical manifestations not included in the classification criteria, such as haematologic manifestations (thrombocytopenia and haemolytic anaemia), neurologic manifestations (chorea, myelitis and multiple sclerosis-like lesions), and nephropathy and heart valve disease associated with antiphospholipid antibodies (aPL), as well as the possible withdrawal of anticoagulation treatment in selected cases of thrombotic APS in which assays for aPL become persistently negative. This Review focuses on the current recommendations for thrombotic and obstetric manifestations of APS, as well as the management of difficult cases. Some aspects of treatment, such as secondary prophylaxis of venous thrombosis, are based on strong evidence--the 'lights' of APS treatment. Conversely, other areas, such as the treatment of non-criteria manifestations of APS, are based only on expert consensus or common sense and remain the 'shadows' of APS therapy. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a disorder characterized by the association of arterial or venous thrombosis and/or pregnancy morbidity with the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant antibodies, and/or anti-β2-glycoprotein I antibodies). Thrombosis is the major manifestation in patients with aPLs, but the spectrum of symptoms and signs associated with aPLs has broadened considerably, and other manifestations, such as thrombocytopenia, non-thrombotic neurological syndromes, psychiatric manifestations, livedo reticularis, skin ulcers, hemolytic anemia, pulmonary hypertension, cardiac valve abnormality, and atherosclerosis, have also been related to the presence of those antibodies. Several studies have contributed to uncovering the basis of antiphospholipid antibody pathogenicity, including the targeted cellular components, affected systems, involved receptors, intracellular pathways used, and the effector molecules that are altered in the process. Therapy for thrombosis traditionally has been based on long-term oral anticoagulation; however, bleeding complications and recurrence despite high-intensity anticoagulation can occur. The currently accepted first-line treatment for obstetric APS (OAPS) is low-dose aspirin plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). However, in approximately 20% of OAPS cases, the final endpoint, i.e. a live birth, cannot be achieved. Based on all the data obtained in different research studies, new potential therapeutic approaches have been proposed, including the use of new oral anticoagulants, statins, hydroxychloroquine, coenzyme Q10, B-cell depletion, platelet and TF inhibitors, peptide therapy or complement inhibition among others. Current best practice in use of these treatments is discussed. [ABSTRACT FROM AUTHOR]

Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and compared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT-derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equivalent was less frequently observed in the APS patients (55.6 vs. 67.8 %; p = 0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)-calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants compared with the APL-negative controls. In conclusion, monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients. [ABSTRACT FROM AUTHOR]

Among the so called antiphospholipid (aPL) antibodies Lupus Anticoagulant (LAC) is considered the strongest risk factor for thromboembolic events. In individuals without a previous thromboembolic event (carriers), LAC is a risk factor when associated with the presence of anticardiolipin (aCL) and aβ2-Glycoprotein I (aβ2GPI) antibodies. On the other hand, data on carriers of isolated LAC positivity are sparse and inconclusive. The aim of this study was to prospectively determine the incidence of thrombosis in a cohort of carriers of isolated LAC positivity. One-hundred seventy-nine carriers of LAC confirmed twelve weeks apart and in a reference laboratory were studied. During a total follow up of 552 person-years, there were seven thromboembolic events (1.3% person-y). All the seven patients had at least one adjunctive major risk factor for thrombosis. The cumulative incidence of thromboembolic events was 3.1% (95% CI 0.6-5.6) after 2years, and 5.9% (95% CI 1.2-10.6) after 5 and 10years. On a multivariate regression analysis considering age, sex, autoimmune disease, risk factors for arterial and venous thrombosis, use of aspirin, only age was found to be an independent predictor of thromboembolic events (HR=1.1, 95% CI 1.0-1.2, p=0.02). These data might be relevant in clinical practice and underline the importance of differentiating LAC carriers in terms of isolated positivity or positivity associated with the presence of antibodies to aCL and β2-glycoprotein I. [ABSTRACT FROM AUTHOR]

The article looks at a research which focuses on complexity related to demonstration of an antiphospholipid antibody by the lupus anticoagulants (LA) assay in antiphospholipid syndrome (APS), an autoimmune disorder associated with hypercoagulability. Topics discussed include heparin neutralization for a prolonged partial thromboplastin time (PTT), coagulation testing characteristics and LA identification to culminate in less secondary testing and guide appropriate antithrombotic therapy.

A main goal in clinical management of patients with antiphospholipid syndrome (APS) is to prevent thrombotic recurrences and/or miscarriages. For many decades, the only available oral anticoagulant drugs have been vitamin K antagonists (VKA), which are still the cornerstone of long-term treatment of thromboembolism. However, the limits of VKA treatment are well known: narrow therapeutic window and high patient-to-patient variability of response. Moreover, in some patients with APS a higher international normalized ratio (INR) therapeutic target was suggested, and INR inaccuracy due to antiphospholipid antibodies was reported. Therefore, VKA management in APS patients is frequently cumbersome, requires close INR monitoring and may affect patient’s quality of life. A new class of oral anticoagulant agents has been developed, the Direct Oral Anticoagulants (DOA), which directly inhibit a single enzyme of the coagulation cascade. Compared with VKA, they have more stable pharmacokinetic and pharmacodynamic profiles, little interaction with food or drugs with a predictable anticoagulation effect, they can thus be prescribed in a fixed dose, without requiring frequent laboratory monitoring. The efficacy and safety of DOA has been shown in large phase III clinical trials. Unfortunately, translating these good results to APS patients is not straightforward: currently, at least three randomized controlled clinical trials are ongoing. [ABSTRACT FROM PUBLISHER]

Abstract: The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed. [Copyright &y& Elsevier]

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved. [ABSTRACT FROM AUTHOR]

Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval [CI], 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Anedoctal reports suggest that some thrombotic primary antiphospholipid antibody syndrome (PAPS) patients on oral anticoagulation require higher than average doses to achieve given targets international normalized ratios (INR). Materials and methods: To test the hypothesis of relative warfarin resistance in thrombotic PAPS and the effect of baseline IgG anticardiolipin antibodies, the cytochrome CYP2C9 and the vitamin K epoxide reductase (VKORC1) haplotypes we compared weekly warfarin consumption of 40 TPAPS (mean age 44±16years) with that of 65 thrombotic patients with inherited thrombophilia (IT) (mean age 52±18) at similar target INR 2.0-3.0 followed up between January-1994 and January 2003. To investigate an involvement of the epoxidation pathway in this difference and to assess enhanced residual fibrin turnover decarboxylated prothrombin (PIVKA-II) and D-dimers (DD) were cross-sectionally investigated in the same patients between March and May 2008. Results: CEX7 and VKORC1 polymorphisms explained 45.1% of the variability in warfarin consumption, whose age-adjusted mean weekly consumption was greater in PAPS than IT (27.62 vs 21.24mg, p=0.03). In PAPS baseline IgG aCL and VKORC1 predicted weekly warfarin consumption (p=0.028 and p=0.024). IgG β2GPI and warfarin dose independently predicted plasma PIVKA-II (p=0.01 and p=0.02). Age and sex adjusted DD was greater in PAPS than IT (132±34 vs 83±37mg/dl, p=0.03). Conclusions: Thrombotic PAPS exhibit a degree of warfarin resistance partly accounted by antiphospholipid antibodies and are in a state of enhanced fibrin turnover despite oral anticoagulation that might have implications for re-thrombosis and atherosclerosis. [Copyright &y& Elsevier]

Persistently positive antiphospholipid antibodies in association with thromboses and/or pregnancy morbidity is the hallmark of the antiphospholipid syndrome. The management of antiphospholipid antibody-positive patients has been focused on utilizing anti-thrombotic medications such as heparin or warfarin. Given that our understanding of the molecular mechanisms of antiphospholipid antibody-mediated thrombosis has been growing, it is highly likely that the current 'anti-thrombotic' approach to these patients will be replaced by an 'immunomodulatory' approach in the near future. This review article will address the experimental and/or clinical evidence behind some of these potential 'immunomodulatory' approaches (tissue factor inhibition, P38 mitogen-activated protein kinase inhibition, nuclear factor-κB inhibition, platelet glycoprotein receptor inhibition, hydroxychloroquine, statins, inhibition of β2GPI and/or anti-β2GPI binding to target cells, complement inhibition, and B cell inhibition) in antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

The classical clinical picture of the antiphospholipid syndrome (APS) is characterized by venous or arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant, anticardiolipin antibodies or antibodies directed to various proteins, mainly β2 glycoprotein 1, or all three. Apart from being "primary" (without any discernable underlying systemic autoimmune disease), or associated to another disease (usually to systemic lupus erythematosus), it may also occur rapidly over days or weeks when it has been termed "catastrophic" APS. Therapy should not primarily be directed at effectively reducing the aPL levels and the use of immunotherapy (including high dose steroid administration, immunosuppression or plasma exchange) is generally not indicated, unless in the catastrophic APS. Treatment of APS patients should be based on the use of antiaggregant and anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Background and aims Antiphospholipid Syndrome (APS) is often complicated by ischemic vascular events. Vitamin K Antagonists (VKAs) reduce the risk of recurrent thrombosis. Quality of VKAs treatment, as assessed by the Time in Therapeutic Range (TTR), has never been investigated in APS patients. Methods We performed a prospective observational study including 30 APS and 30 Atrial Fibrillation (AF) patients balanced by age and gender. All patients were treated with VKAs (INR target 2.5), and TTR was calculated. Results Median TTR of APS was 53.5% vs. 68% of AF patients (p = 0.001). A multivariable linear regression analysis confirmed that the presence of APS (vs. AF) was independently associated with a worse TTR (B: −14.067, 95% Confidence Interval −25.868/−2.266, p = 0.020). The weekly dosage of VKAs was significantly higher in APS than AF patients. Conclusions APS patients disclose a lower quality of anticoagulation compared to those with AF, requiring higher doses of VKAs. The efficacy of non-vitamin K oral anticoagulants in this high-risk patients should be tested. [ABSTRACT FROM AUTHOR]

Abstract: Antiphospholipid syndrome (APS) is characterised by vascular thrombosis and/or obstetric morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Balancing an individuals'' risk of thrombosis against the benefits and risks of antithrombotic therapies is crucial for optimising management and preventing morbidity in APS and asymptomatic aPL. Limitations in research studies have led to debate regarding best-practice. This review of the available literature makes the following recommendations. Those with asymptomatic aPL should only be treated with aspirin if they have persistently positive aPL, obstetric APS, or co-existent systemic lupus erythematosus. For those with APS, lower risk patients (i.e. first venous thrombosis) should be treated with warfarin to an INR 2.0–3.0. Those at higher risk (i.e. arterial thrombosis or recurrent events) should be treated with warfarin to an INR of >3.0. During pregnancy in APS, low molecular weight heparin (LMWH) and aspirin should be used and women should be under the care of obstetricians and physicians specialising in APS. Additional vascular and thrombotic risk factors should be actively reduced in all patient groups. Further randomised controlled trials are required, which should involve larger patient groups with APS diagnosed according to accepted criteria. This may mean that international and multi-centre trials are needed to ascertain the best treatment regimens. [Copyright &y& Elsevier]

This report considers the rare situation in which primary antiphospholipid syndrome (PAPS) is linked with thrombotic thrombocytopenic purpura (TTP). It describes the case of a young lady with PAPS, characterized by recurring cerebro-vascular abnormalities and marked livedo reticularis, combined with circulating anticardiolipin and lupus anticoagulant antibodies. On follow-up, while on oral anticoagulation, she developed severe thrombocytopenia associated with hematuria, microangiophatic anaemia and neurological manifestations consistent with a diagnosis of TTP. The patient was treated with pulses of methylprednisolone and plasmapheresis with plasma exchange. The result was a favourable outcome. To our knowledge, this is the seventh report on this rare association in the English-language literature of this field. [ABSTRACT FROM AUTHOR]

To examine the clinical manifestations, intensity of oral anticoagulation and outcomes in the prevention of recurrent thromboses in patients with antiphospholipid syndrome (APS) in a tertiary rheumatology centre in Singapore. Retrospective case review of consecutive patients with APS attending a rheumatology clinic from 1st January 2004 to 31st December 2005. There were 59 (44%) patients with definite APS and 75 (56%) with probable APS. Systemic lupus erythematosus (SLE) was the most common cause of secondary APS. Hypertension and hyperlipidaemia were the most common cardiovascular comorbidities. The most common manifestations were haematological (thrombocytopaenia and haemolytic anaemia), neurological (seizure, headache) and pulmonary hypertension. Among those with definite APS, there were similar proportions with arterial and venous thromboses. Recurrent thromboses occurred in 14 (23.7%) patient with definite APS receiving warfarin, comprising 14 (73.7%) episodes of arterial and 5 (26.3%) episodes of venous thromboses. Recurrent arterial thromboses occurred at international normalized ratio (INR) of <2 in 5 (35.7%), INR 2-3 in 6 (42.9%), INR > 3 in 3 (21.4%) episodes, respectively. Recurrent venous thromboses occurred at INR < 2 in 4 (80.0%) and INR > 3 in 1 (20.0%) episode, respectively. Twenty-eight episodes of bleeding occurred in 21 (35.6%) patients, the majority (78.6%) being minor bleeding. Two-thirds of all major bleeds occurred at INR = 3. Venous and arterial thromboses were equally common in our patients with definite APS, although recurrent thromboses were more common in the arterial circulation. Target INR > 3 was associated with lower rates of recurrent arterial thromboses but higher rates of major and recurrent bleeding. Target INR ≥ 2 appeared to be sufficient to prevent recurrent venous thromboses. [ABSTRACT FROM AUTHOR]

Purpose. The quality of anticoagulation therapy in patients with antiphospholipid syndrome (APS) was evaluated. Summary. The high risk of unnecessary anticoagulation and recent changes in the recommended International Normalized Ratio (INR) target range prompted a performance-improvement initiative to improve the care of patients with APS within the University of Iowa Hospitals and Clinics internal medicine and family medicine anticoagulation clinics. Twenty-three patients with an initial diagnosis of APS were evaluated through chart review to determine the anticoagulation indication, occurrence of thromboembolic events, and INR target range. Confirmation of APS diagnosis was made using Sapporo criteria. Recommendations were made to the patients' physicians for confirmatory APS testing and changes in the anticoagulation regimen. INR target ranges were 2.0–3.0, 2.5–3.5, and 2.5–3.0 for 57%, 39%, and 4% of patients, respectively. Only 6 (26%) of the 23 patients met Sapporo criteria for a definite diagnosis of APS. Of the 17 patients (74%) who did not meet these criteria, 8 (47%) had another indication for indefinite anticoagulation. Repeat APS testing was indicated for 7 patients, 5 of whom met Sapporo criteria for APS. A lower target INR range of 2.0–3.0 was determined appropriate for 6 (26%) of the 23 patients evaluated. Conclusion. A majority of patients with an initial diagnosis of APS did not meet criteria for a definite diagnosis of APS. Of those patients, approximately half had another indication for long-term anticoagulation, and one third were receiving warfarin dosages based on an INR target range that was higher than clinically indicated. [ABSTRACT FROM AUTHOR]

Thrombotic events associated with antiphospholipid (aPL) antibodies can be the first manifestation of malignancy. The pathologic significance of aPL antibodies in patients with malignancies, however, is still unclear. It remains an unresolved issue as to whether the presence of aPL antibodies may be considered as an "epiphenomenon" of the malignancy itself or whether it contributes directly to the development of thrombosis in these patients. In particular, solid tumors may be associated with the development of aPL antibodies, enhancing the thrombophilic risk in these patients. In general, routine anticoagulant prophylaxis with low-molecular-weight heparin in cancer patients with positive aPL antibodies is strongly indicated. [ABSTRACT FROM AUTHOR]

Background: Prolonged anticoagulation is the treatment of choice for patients with thrombosis and the antiphospholipid syndrome. However, there is still debate about the optimum intensity of anticoagulation. Methods: The study included 66 patients with antiphospholipid syndrome (Sapporo criteria) and previous thrombosis. All were receiving oral anticoagulation to a target international normalized ratio of 3.5. Every patient was individually interviewed to recall major bleeding and thrombotic episodes during the previous 12 months. Results: Patients were mainly women and white. The rate of major bleeding was 6 cases per 100 patient-years (95% confidence interval [CI] 1.6-15.0). The rate of intracranial bleed was 1.5 per 100 patient-years (95% CI, 0.04-8.4). None of the bleeding episodes was fatal. The rate of thrombotic recurrences was 9.1 cases per 100 patient-years (95% CI, 3.3-19.6). Most recurrences took place in the same vascular bed as the original thrombosis. Age, time receiving anticoagulant therapy, primary vs secondary antiphospholipid syndrome, positivity for anticardiolipin antibodies, positivity for lupus anticoagulant, previous artenal thrombosis, previous stroke, previous venous thrombosis, and previous thrombocytopenia were not predictive of bleeding events. However, the risk of thrombotic recurrences was independently higher in patients who were receiving anticoagulation for longer periods. Conclusions: The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses. [ABSTRACT FROM AUTHOR]

Because of the variable responsiveness of thromboplastins to lupus anticoagulants (LA), concerns have been raised about the validity of the prothrombin time–International Normalized Ratio (PT–INR) in monitoring oral anticoagulant treatment in patients with the antiphospholipid syndrome (APS) and LA. To date, few studies have been performed, numbers of patients investigated are relatively small and results are conflicting. We report on a multicentre study organized to investigate further this clinically relevant issue. Each of nine thrombosis centres was asked to collect plasma samples from patients with APS who were on oral anticoagulants (cases) and patients without APS who were on oral anticoagulants (controls). Nine thromboplastins (three human recombinant, one from human placenta and five from rabbit brain) were calibrated at the co-ordinating centre according to World Health Organization guidelines. Measurements of the INR and factor X amidolytic activity for all frozen plasmas were performed centrally. The numbers of patients investigated were 58 cases and 57 controls. Between-reagent variability of the INR was higher in cases [coefficient of variation (CV) = 12·4%] than in controls (CV = 6·7%), but this was because of one of the thromboplastins only (Thromborel R, human recombinant), which measured considerably higher INR values than the others in cases but not in controls. In conclusion, our data indicate that LA interference on the PT–INR measured with the majority of commercial thromboplastins is not enough to cause concern if insensitive thromboplastins, properly calibrated to assign them an instrument-specific International Sensitivity Index are used. New thromboplastins, especially those made of relipidated tissue factor, should be checked for their responsiveness to LA before they are used to monitor oral anticoagulant treatment in patients with APS. [ABSTRACT FROM AUTHOR]

We report three cases of severe haemorrhagic rupture of luteal ovarian cyst requiring surgical haemostasis in young women treated with long-term oral anticoagulation for antiphospholipid syndrome (APS) who used no contraception. At the time of bleeding, the international normalized ratios were 3.78, 4.24, and 7.11. Anticoagulation was resumed post-operatively, in association with antigonadotropic progestins to induce ovulatory suppression. A systematic use of these progestins should probably be discussed in young women receiving long-term warfarin for APS. Ovarian haemorrhage must be considered when such patients develop acute abdominal pain. [ABSTRACT FROM AUTHOR]

Focuses on the topics discussed at the European Forum on Antiphospholipid Antibodies (aPL) in New Orleans in October 1996. Biological heterogeneity of aPL; Use of oral anticoagulants in the prevention of recurrent thrombosis in patients with antiphospholipid syndrome; Hypothesis on pathogenicity and clinical relevance of aPL.

Heart valve disease (HVD) is the most common cardiac manifestation in the antiphospholipid syndrome (APS). Valve lesions should be described according to the established definition. HVD is progressive despite anticoagulant/antiplatelet treatments. Around 4–6% of patients with HVD in APS will require valve replacement surgery, which is considered a very high risk procedure in APS. Unfortunately, no recommendations regarding medical treatment of antiphospholipid antibodies-associated HVD can be made at this moment. There are evidence-based data and strong pathophysiologic rationale for considering HVD as a manifestation of APS. Thus, HVD should be included as a criterion of definite APS. [ABSTRACT FROM PUBLISHER]