Diagnosis and Management of the Antiphospholipid Syndrome

García, David; Erkan, Doruk

doi:10.1056/nejmra1705454

Cited by 544 publications

(537 citation statements)

References 67 publications

Supporting

Mentioning

482

Contrasting

Unclassified

Order By: Relevance

“…[16][17][18] Common indications for further testing include prolongation of APTT with or without clinical symptoms indicative of antiphospholipid syndrome or systemic autoimmune disease. 15,19 A high-risk antiphospholipid antibody testing profile is defined by the presence of a positive lupus anticoagulant test, 19 and especially triple positivity for antiphospholipid antibodies (lupus anticoagulants, anticardiolipin, and anti-β 2 -glycoprotein I antibodies). 20,21 Triple positivity has been associated with a high thrombotic risk and may require long-term anticoagulation to prevent recurrence after the first thrombotic episode.…”

Section: Lupus Anti Coag Ul Antsmentioning

confidence: 99%

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini‐review

Rasmussen

Philips

Tripodi

et al. 2020

European J of Haematology

View full text Add to dashboard Cite

A common inquiry in coagulation laboratories is how to interpret an unexpected, isolated prolonged activated partial thromboplastin time (APTT). In this context, isolated means together with a normal prothrombin time (PT) and/or normal international normalized ratio (INR). This finding may lead to contact with laboratory doctors for further advice on a diagnostic strategy. Occasionally, the need for a diagnostic algorithm can be subacute, where surgery has to be postponed until an explanation for the isolated, prolonged APTT has been established. Activated partial thromboplastin time as a coagulation test was developed to monitor patients with hemophilia.Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors. An isolated, prolonged APTT is seen in (a) individuals/patients with lupus anticoagulants, (b) patients in treatment with anticoagulants, mainly heparin, and (c) patients with deficiencies of specific coagulation factors. In this tutorial review, we summarize what may cause an isolated prolonged APTT and we present a simple diagnostic algorithm to differentiate between lupus anticoagulants (common) and factor deficiencies (rare). The identification of an isolated prolonged APTT as well as the underlying cause can be of the utmost importance in ensuring the correct therapeutic follow-up. K E Y W O R D Sactivated partial thromboplastin time, hemophilia, lupus anticoagulants

show abstract

Section: Lupus Anti Coag Ul Antsmentioning

confidence: 99%

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini‐review

Rasmussen

Philips

Tripodi

et al. 2020

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…Antiphospholipid syndrome (APS) is an autoimmune condition of unknown cause and is defined by the presence of circulating antiphospholipid antibodies (aPLs; anticardiolipin, anti–β 2 ‐glycoprotein I [anti‐β 2 GPI], or lupus anticoagulant [LAC]) . The morbidity and mortality of APS are significant, as patients carry a markedly increased risk of thrombotic events (especially stroke and deep vein thrombosis) and pregnancy loss . Beyond these disease‐defining events, patients with APS may also develop cytopenias, heart valve damage, nephropathy, and cognitive dysfunction, among other complications .…”

Section: Introductionmentioning

confidence: 99%

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1

Sule

Kelley

Gockman

et al. 2019

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective While the role of antiphospholipid antibodies in activating endothelial cells has been extensively studied, the impact of these antibodies on the adhesive potential of leukocytes has received less attention. This study was undertaken to investigate the extent to which antiphospholipid syndrome (APS) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion. Methods Patients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells (HUVECs). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellular trap release (NETosis) was assessed in neutrophil‐HUVEC cocultures. Results Upon perfusion of anticoagulated blood through the flow chamber, APS neutrophils demonstrated increased adhesion as compared to control neutrophils under conditions representative of either venous (n = 8; P < 0.05) or arterial (n = 15; P < 0.0001) flow. At the same time, APS neutrophils were characterized by up‐regulation of CD64, CEACAM1, β2‐glycoprotein I, and activated Mac‐1 on their surface (n = 12–18; P < 0.05 for all markers). Exposing control neutrophils to APS plasma or APS IgG resulted in increased neutrophil adhesion (n = 10–11; P < 0.0001) and surface marker up‐regulation as compared to controls. A monoclonal antibody specific for activated Mac‐1 reduced the adhesion of APS neutrophils in the flow‐chamber assay (P < 0.01). The same monoclonal antibody reduced NETosis in neutrophil–HUVEC cocultures (P < 0.01). Conclusion APS neutrophils demonstrate increased adhesive potential, which is dependent upon the activated form of Mac‐1. In patients, this could lower the threshold for neutrophil–endothelium interactions, NETosis, and possibly thrombotic events.

show abstract

“…Antiphospholipid syndrome (APS) is a systemic autoimmune disease associated with thrombotic or obstetrical events in patients with persistent immunoglobulin (Ig)G or IgM antiphospholipid antibodies (aPL) . Laboratory classification criteria for definite APS include detection of persistent lupus anticoagulant (LA) activity and/or medium to high levels of anticardiolipin (aCL) and/or anti‐β2‐glycoprotein I (aβ2GPI) antibodies . Triple positive APS, including the positive LA and high titers of aCL and aβ2GPI antibodies, instead of individual test positivity, are associated with up to 30‐fold higher risk of thrombosis .…”

Section: Introductionmentioning

confidence: 99%

“…1 Laboratory classification criteria for definite APS include detection of persistent lupus anticoagulant (LA) activity and/or medium to high levels of anticardiolipin (aCL) and/ or anti-β2-glycoprotein I (aβ2GPI) antibodies. 1 Triple positive APS, including the positive LA and high titers of aCL and aβ2GPI antibodies, instead of individual test positivity, are associated with up to 30-fold higher risk of thrombosis. 2,3 Although prothrombin is a known antigenic target for aPL antibodies and previous studies have shown that 50% to 90% of aPL-positive patients present antibodies reacting against prothrombin, 4 positive antiprothrombin antibodies have not been yet included in the guidelines as the APS classification criteria.…”

Section: Introductionmentioning

confidence: 99%

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Ząbczyk

Celińska-Löwenhoff

Plens

et al. 2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are recognized as a marker for antiphospholipid syndrome (APS). Dense and poorly lysable fibrin clots occur in thrombotic APS. Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS. We hypothesized that elevated aPS/PT antibodies determine unfavorable clot features. Methods In a cohort study involving 124 consecutive patients with thrombotic APS, we measured at baseline plasma fibrin clot permeability (Ks), efficiency of fibrinolysis (clot lysis time, CLT), and turbidity (off anticoagulation) along with immunoglobulin (Ig)G/IgM aPS/PT. During follow‐up, symptomatic thromboembolic events were recorded. Results Elevated IgG and IgM aPS/PT antibodies >30 international enzyme units (UI) were detected in 54.8% and 42.7% of APS patients, including 76.2% and 54% of lupus anticoagulant‐ (LA, n = 63) positive patients, respectively. Elevated IgG and IgM aPS/PT antibodies predicted low Ks (lower quartile, <6 × 10−9 cm2; odds ratio [OR] = 5.93, 95% confidence interval [CI] 2.09‐16.82 and OR = 11.79, 95% CI 4.10‐33.92) and prolonged CLT (top quartile, ≥116 min; OR = 4.85, 95% CI 2.42‐25.07 and OR = 6.04, 95% CI 2.42‐15.07). No such associations were observed for anticardiolipin or β2‐glycoprotein I antibodies or LA presence. During follow‐up (median 72.5, range 66‐83 months), thromboembolic events observed in 32 (26.7%, 4.6%/year) patients were independently predicted by IgG aPS/PT antibodies >30 UI (hazard ratio [HR] = 3.04, 95% CI 1.20‐8.88) and low Ks (HR = 3.00, 95% CI 1.41‐6.50). Conclusions We identified aPS/PT antibodies as a determinant of denser and poorly lysable plasma fibrin clot formation in APS patients. The association of elevated aPS/PT antibodies with thromboembolism in APS could be at least in part mediated by prothrombotic clot properties.

show abstract

Diagnosis and Management of the Antiphospholipid Syndrome

Cited by 544 publications

References 67 publications

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini‐review

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini‐review

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Contact Info

Product

Resources

About