Anti-phospholipid antibody syndrome

2015 ◽  
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Fetal Death ◽  
Clinical Manifestations ◽  
Obstetric Care ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

Anti-phospholipid antibody syndrome

2013 ◽  
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Fetal Death ◽  
Clinical Manifestations ◽  
Obstetric Care ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

Anti-phospholipid antibody syndrome

2013 ◽  
pp. 957-968
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Clinical Manifestations ◽  
Obstetric Care ◽  
Recurrent Miscarriages ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

Antiphospholipid antibody profile: implications for the evaluation and management of patients

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 432-435 ◽  
Author(s):  
A. Tincani ◽  
L. Andreoli ◽  
C. Casu ◽  
R. Cattaneo ◽  
P. Meroni
Keyword(s):  
Pregnancy Loss ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Diagnostic Value ◽  
Antiphospholipid Antibody ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Antibody Assays ◽  
Independent Risk Factors ◽  
Deep Vein

According to the classification criteria of antiphospholipid syndrome, lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I antibody assays are independent risk factors for the occurrence of vascular thrombosis and pregnancy loss. However, it is generally accepted that patients carrying multiple positivity have more a severe disease and higher recurrence rate despite treatment. On the other hand, the diagnostic value of a positive result in one only assay is more controversial, particularly in the presence of clinical manifestations such as deep vein thrombosis or early miscarriages, which are rather common in the general population. In this review we speculate on current and future strategies to interpret different antiphospholipid antibody profiles in the clinical practice. Lupus (2010) 19, 432—435.

scholarly journals Anti-Phosphatidylserine/Prothrombin Antibodies at Two Points: Correlation With Lupus Anticoagulant and Thrombotic Risk

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalia Egri ◽  
Chelsea Bentow ◽  
Laura Rubio ◽  
Gary L. Norman ◽  
Susana López-Sañudo ◽  
...  
Keyword(s):  
Lupus Anticoagulant ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Risk Markers ◽  
Thrombotic Risk ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Pt Complex ◽  
Associated Proteins ◽  
Anti Phospholipid Syndrome

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (β2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) &gt; than 9 points (p &lt; 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.

scholarly journals O09 Safety profile of baricitinib for the treatment of RA up to 8.4 years: an updated integrated safety analysis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Kevin L Winthrop ◽  
Tsutomu Takeuchi ◽  
Gerd Burmester ◽  
Walter Deberdt ◽  
Douglas Schlichting ◽  
...  
Keyword(s):  
Safety Profile ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Stock Ownership ◽  
Research Support ◽  
Vein Thrombosis ◽  
Non Melanoma Skin Cancer ◽  
Deep Vein

Abstract Background/Aims  Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1/2, approved for treatment of moderate-to-severe- rheumatoid arthritis (RA) in adults. Here, we update the drug’s safety profile with data up to 8.4 years of treatment. Methods  Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study. Incidence rates(IRs) per 100 patient-years (PY) were calculated for all RA patients treated with ≥1 dose of BARI through 1-Sep-2019(All-BARI-RA set). IRs for deep vein thrombosis(DVT), pulmonary embolism(PE), and DVT and/or PE(DVT/PE) were also calculated for groups of patients while receiving BARI 2mg/4mg within All-BARI-RA. Major adverse cardiovascular events(MACE) were adjudicated in 5 Ph3 studies and the LTE. Results  3770 pts received BARI for 13,148 PY, with median and maximum exposure: 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.46)(excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.46); malignancies excluding non-melanoma skin cancer (NMSC)(0.91); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). (IRs)[95% confidence intervals] for patients while receiving BARI 2mg (N = 1077) and BARI 4mg (N = 3400) were DVT 2mg (0.38)[0.18, 0.73] and 4mg (0.30)[0.21, 0.43]; PE 2mg (0.26)[0.09, 0.56] and 4mg (0.25)[0.16, 0.36]; and DVT/PE 2mg (0.47)[0.23, 0.84] and 4mg (0.46)[0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time. Across safety topics, IRs were consistent with previous analyses. Conclusion  In this update, with 3021 additional PY of exposure, BARI maintained a safety profile similar to that previously reported, with no increase of IRs across safety topics through exposures up to 8.4 years. Disclosure  K.L. Winthrop: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and UCB Pharma. Grants/research support; Bristol Myers Squibb and Pfizer. T. Takeuchi: Consultancies; AbbVie, Asahi Kasei Medical, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis, Pfizer Japan, Taiho Pharmaceutical, Taiho Toyama Pharmaceutical, Takeda, and UCB Japan. G. Burmester: Consultancies; Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; Eli Lilly and Company. W. Deberdt: Shareholder/stock ownership; Eli Lilly and Company. D. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. D. Mo: Shareholder/stock ownership; Eli Lilly and Company. C. Walls: Shareholder/stock ownership; Eli Lilly and Company. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead Sciences, ILTOO Pharma, Janssen, MedImmune, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB Pharma. Grants/research support; AbbVie, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

scholarly journals Predictors of long-term post-thrombotic syndrome following high proximal deep vein thrombosis: a cross-sectional study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Marit Engeseth ◽  
Tone Enden ◽  
Per Morten Sandset ◽  
Hilde Skuterud Wik
Keyword(s):  
Deep Vein Thrombosis ◽  
Proximal Deep Vein Thrombosis ◽  
Cross Sectional ◽  
Clinical Criteria ◽  
Vein Thrombosis ◽  
Post Thrombotic Syndrome ◽  
Younger Age ◽  
Deep Vein

Abstract Background Post-thrombotic syndrome (PTS) is a frequent chronic complication of proximal deep vein thrombosis (DVT) of the lower limb, but predictors of PTS are not well established. We aimed to examine predictors of PTS in patients with long-term PTS following proximal DVT. Methods During 2006–09, 209 patients with a first time acute upper femoral or iliofemoral DVT were randomized to receive either additional catheter-directed thrombolysis or conventional therapy alone. In 2017, the 170 still-living participants were invited to participate in a cross-sectional follow-up study. In the absence of a gold standard diagnostic test, PTS was defined in line with clinical practice by four mandatory, predefined clinical criteria: 1. An objectively verified DVT; 2. Chronic complaints (> 1 month) in the DVT leg; 3. Complaints appeared after the DVT; and 4. An alternative diagnosis was unlikely. Possible predictors of PTS were identified with multivariate logistic regression. Results Eighty-eight patients (52%) were included 8–10 years following the index DVT, and 44 patients (50%) were diagnosed with PTS by the predefined clinical criteria. Younger age and higher baseline Villalta score were found to be independent predictors of PTS, i.e., OR 0.96 (95% CI, 0.93–0.99), and 1.23 (95% CI, 1.02–1.49), respectively. Lack of iliofemoral patency at six months follow-up was significant in the bivariate analysis, but did not prove to be significant after the multivariate adjustments. Conclusions In long-term follow up after high proximal DVT, younger age and higher Villalta score at DVT diagnosis were independent predictors of PTS.

P6461The long-term clinical comparisons of symptomatic patients of pulmonary embolism with and those without deep vein thrombosis: from the COMMAND VTE Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Murata ◽  
Y Yamashita ◽  
T Morimoto ◽  
H Amano ◽  
T Takase ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Acute Phase ◽  
Clinical Presentation ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Severe Clinical Presentation ◽  
Recurrent Vte ◽  
Deep Vein

Abstract Background Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), has significant morbidity and mortality. Acute PE, in particular, is fatal if we miss it, and symptomatic patients of PE sometimes have concomitant DVT. Purpose This study compared the risk of mortality in symptomatic patients of PE with and those without DVT in the long term. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. Patients with both PE and DVT (N=1334) were regarded as PE patients, and the current study population consisted of 1715 PE patients and 1312 DVT patients. Results There were 1203 symptomatic patients of PE, including 381 without and 822 with DVT. In our cohort, the mean age was 67.9±14.9 years, 63% was female, 44% had hypertension, 12% diabetes mellitus, 5% history of VTE. There were 20% of active cancer. Baseline characteristics were well matched except for dyslipidemia (18% vs. 23%, p=0.021) and atrial fibrillation (8% vs. 5%, p=0.045). Patients without DVT had a more severe clinical presentation compared to those with DVT, including hypoxemia, shock and arrest. Moreover, Initial parenteral anticoagulation therapy in the acute phase was administered less frequently in patients without DVT (89% vs. 96%, P=0.0001). Two groups received thrombolysis (20% vs. 26%, P=0.18) and mechanical supports (Ventilator 14% vs. 5%, p<0.001, PCPS 5% vs. 3%, p<0.001, respectively). During follow-up, 93 (8%) patients experienced recurrent VTE events and 98 (8%) major bleeding events, and 323 (27%) patients died. The most frequent cause of death was cancer (11%). There were a significant differences in the cumulative incidences of all-cause death between the groups (32% vs. 24%, P=0.006), whereas there was significant difference in VTE-related death (13% vs. 4%, p<0.001). Estimated freedom rates from death for patients of PE without and those with DVT were as follows: 88% vs 99% at 10-day, 86% vs 95% at 1-month, 75% vs 83% at 1-year, and 64% vs 71% at 5-year, respectively. Landmark analysis Conclusions In symptomatic patients of PE, there was a difference in mortality between groups, but no difference in recurrent VTE. Patients without DVT had a more severe clinical presentation compared to those with DVT, and many VTE-related deaths in the acute phase. The one-month mortality rate differed statistically between groups, but there was no significant difference in long-term survival beyond one month. Most of deaths were due to underlying diseases, mainly cancer, and less commonly due to VTE in the long term. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Atrial fibrillation associated with increased risk of venous thromboembolism

2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

scholarly journals Economic Analysis of Rivaroxaban for the Treatment and Long-Term Prevention of Venous Thromboembolism in Portugal

2014 ◽  
Vol 27 (5) ◽  
pp. 615 ◽  
Author(s):  
Isabel Fonseca Santos ◽  
Sónia Pereira ◽  
Euan McLeod ◽  
Anne-Laure Guillermin ◽  
Ismini Chatzitheofilou
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Standard Of Care ◽  
Quality Adjusted Life Years ◽  
Vein Thrombosis ◽  
Scenario Analyses ◽  
Life Years ◽  
Deep Vein ◽  
Quality Adjusted Life

<p><strong>Introduction:</strong> Venous thromboembolism is a burden on healthcare systems. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (enoxaparin/warfarin) in Portugal for the treatment and secondary prevention of venous thromboembolism.<br /><strong>Material and Methods:</strong> A Markov model was developed using event rates extracted from the EINSTEIN trials supplemented with literature-based estimates of longer-term outcomes. Core outcomes included per patient costs and quality-adjusted life years reported separately per treatment arm and incrementally, as well as cost per quality-adjusted life years gained. The deep vein thrombosis and pulmonary embolism indications were analysed separately. The analyses were conducted from the Portuguese societal perspective and over a 5-year time horizon. Costs and outcomes were discounted at a 5% annual rate. Several scenario analyses were undertaken to explore the impact on results of varying key modeling assumptions.<br /><strong>Results:</strong> Rivaroxaban treatment was associated with cost-savings for the treatment of deep vein thrombosis and was both cost-saving and more effective for the treatment of pulmonary embolism, compared with enoxaparin/warfarin.<br /><strong>Discussion:</strong> The results of the sensitivity and scenario analyses further supported that rivaroxaban is a cost-effective alternative to standard of care treatment. The use of an expert panel to derive some input values and the lack of Portuguese specific utilities were the main limitations.<br /><strong>Conclusion:</strong> Rivaroxaban represents an efficient alternative to using enoxaparin/warfarin in Portugal, as it’s associated with lower costs (for both indications) and greater quality adjusted life years (for the pulmonary embolism indication).</p><p><br /><strong>Keywords: </strong>Venous Thrombosis; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism.</p>

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