Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS)

Gebhart, Johanna; Posch, Florian; Koder, Silvia; Perkmann, Thomas; Quehenberger, Peter; Zoghlami, Claudia; Ay, Cihan; Pabinger, Ingrid

doi:10.1182/blood-2014-11-611129

Cited by 62 publications

(56 citation statements)

References 41 publications

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“…7, 11 Patients with thrombotic APS are at higher risk for subsequent cardiovascular mortality than patients without these antibodies 138 In the Vienna APS study, a prospective observational cohort, LA positive patients, with or without thrombosis, had higher mortality at 10 years (cumulative relative survival 87%) compared with a reference population matched for age, sex and inclusion year. 140 …”

Section: Management Of Thrombosis In Apsmentioning

confidence: 99%

Diagnosis and management of the antiphospholipid syndrome

2017

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Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed towards phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, and complement activation, among others. There is a high rate of recurrent thrombosis in APS, especially in triple positive patients (patients with lupus anticoagulants, aCL and anti-β2GPI antibodies), and indefinite anticoagulation with a vitamin K antagonist is the standard of care for thrombotic APS. There is currently insufficient evidence to recommend the routine use of direct oral anticoagulants (DOAC) in thrombotic APS. Aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS. Recent insights into the pathogenesis of APS have led to the identification of new potential therapeutic interventions, including anti-inflammatory and immunomodulatory therapies. Additional research is needed to better understand the effects of APLA on activation of signaling pathways in vascular cells, to identify more predictive biomarkers that define patients at greatest risk for a first or recurrent APLA-related clinical event, and to determine the safety and efficacy of DOACs and novel anti-inflammatory and immune-modulatory therapies for refractory APS.

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Section: Management Of Thrombosis In Apsmentioning

confidence: 99%

Diagnosis and management of the antiphospholipid syndrome

2017

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“…Indeed, lupus anticoagulant is the antiphospholipid antibody test that best predicts thrombotic events in classic APS [23]*, and 82% of patients in the CAPS registry have been reported to have a positive lupus anticoagulant [6]. Clinical states that prolong clotting times, such as therapeutic anticoagulation or disseminated intravascular coagulation (DIC), introduce inherent complications (and the potential for false positives) into lupus anticoagulant testing.…”

Section: Diagnosismentioning

confidence: 99%

Treatment of catastrophic antiphospholipid syndrome

Kazzaz

McCune

Knight

2016

Current Opinion in Rheumatology

109

113

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Purpose of review Catastrophic antiphospholipid syndrome (CAPS) is a severe manifestation of APS. While affecting only 1% of patients with APS, the condition is frequently fatal if not recognized and treated early. Here, we will review the current approach to diagnosis and treatment of CAPS. Recent findings Data from the international “CAPS registry,” spearheaded by the European Forum on Antiphospholipid Antibodies, have improved our understanding of at-risk patients, typical clinical features, and associated/precipitating diagnoses. Current guidelines also continue to support a role for anticoagulants and glucocorticoids as foundation therapy in all patients. Finally, new basic science and case series suggest that novel therapies, such as rituximab and eculizumab warrant further study. Summary Attention to associated diagnoses such as infection and systemic lupus erythematosus (SLE) are critical at the time of diagnosis. All patients should be treated with anticoagulation, corticosteroids, and possibly plasma exchange. In patients with SLE, cyclophosphamide should also be considered. In refractory or relapsing cases, new therapies such as rituximab and possibly eculizumab may be options, but need further study.

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“…A poor survival rate was not associated with the presence of aCLs and anti-b2GPI antibodies, prior history of thrombosis or pregnancy complications, or prior diagnosis of an autoimmune rheumatic disease in their cohort. 1 In conclusion, Gebhart et al have clearly shown that the young female patient with LA described above is at increased risk for thrombosis. Our ability to identify higher-risk patients may be improved by better definition of risk factors for thrombosis other than LA and by improved understanding of the unique aspects of the pathophysiology of thrombosis in APS patients.…”

mentioning

confidence: 73%

“…In the present study, Gebhart et al prospectively investigated 151 LA-positive patients for a median of 8 years. 1 At the beginning of the study, 39 patients had no clinical findings attributed to an autoimmune disease (as in scenario 1), 112 patients were diagnosed with APS, and 29 patients had concomitant systemic lupus erythematosus (as in scenario 3). Thirty patients (20%) experienced thromboembolic events during follow-up; 14 of them were arterial thrombosis.…”

mentioning

confidence: 99%

Lupus anticoagulant, thrombosis, and death

Diz‐Küçükkaya

2015

Blood

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inhibitors. The possibility also exists that other mutant oncoproteins implicated in leukemogenesis, and for which specific inhibitors are not yet available, could represent additional targets for this strategy.There are, however, several questions and caveats that could clearly determine the potential of this approach. For example, it remains to be established whether the ATRA/ATO strategy targets mutant NPM1-expressing leukemia-initiating cells (stem cells) which, at least theoretically, could be responsible for disease relapse. In addition, although both cultured and primary NPM1-mutant AML cells were very susceptible to this regimen, it is less certain whether the degree of cell killing can approximate that observed in the case of APL cells. Finally, although the ATRA/ATO regimen showed some activity in patients with mutant NPM1 AML, it is generally recognized that survival benefits in this (or other) disease(s) absent objective complete responses are unlikely. In this regard, the finding that ATRA/ATO enhanced the activity of an active anti-leukemic agent (eg, daunorubicin) in mutant NPM1 AML is noteworthy and raises the possibility of a more effective future approach. Alternatively, combining the ATRA/ATO strategy with other targeted therapies, including those directed against NPM1 itself, may provide opportunities for cure in this disease, as observed in some patients with APL. Finally, extrapolation of this strategy to other AML subtypes that display different oncogenic mutant proteins represents a promising possibility and one that clearly deserves further investigation.Conflict-of-interest disclosure: The author declares no competing financial interests. n

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Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS)

Cited by 62 publications

References 41 publications

Diagnosis and management of the antiphospholipid syndrome

Diagnosis and management of the antiphospholipid syndrome

Treatment of catastrophic antiphospholipid syndrome

Lupus anticoagulant, thrombosis, and death

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