Altered fibrin clot structure/function in patients with antiphospholipid syndrome: association with thrombotic manifestation

Magdalena Celińska-Löwenhoff; Teresa Iwaniec; Agnieszka Padjas; Jacek Musiał; Anetta Undas

doi:10.1160/TH13-11-0980

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(02): 287-296
DOI: 10.1160/TH13-11-0980

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Altered fibrin clot structure/function in patients with antiphospholipid syndrome: association with thrombotic manifestation

Authors

Magdalena Celińska-Löwenhoff

¹Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
Teresa Iwaniec

¹Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
Agnieszka Padjas

¹Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
Jacek Musiał

¹Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
Anetta Undas

²Institute of Cardiology Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland

Abstract

Summary

We tested the hypothesis that plasma fibrin clot structure/function is unfavourably altered in patients with antiphospholipid syndrome (APS). Ex vivo plasma clot permeability, turbidity and susceptibility to lysis were determined in 126 consecutive patients with APS enrolled five months or more since thrombotic event vs 105 controls. Patients with both primary and secondary APS were characterised by 11% lower clot permeability (p<0.001), 4.8% shorter lag phase (p<0.001), 10% longer clot lysis time (p<0.001), and 4.7% higher maximum level of D-dimer released from clots (p=0.02) as compared to the controls. Scanning electron microscopy images confirmed denser fibrin networks composed of thinner fibres in APS. Clots from patients with “triple-antibody positivity” were formed after shorter lag phase (p=0.019) and were lysed at a slower rate (p=0.004) than in the remainder. Clots from APS patients who experienced stroke and/or myocardial infarction were 8% less permeable (p=0.01) and susceptible to lysis (10.4% longer clot lysis time [p=0.006] and 4.5% slower release of D-dimer from clots [p=0.01]) compared with those following venous thromboembolism alone. Multivariate analysis adjusted for potential confounders showed that in APS patients, lupus anticoagulant and “triple-positivity” were the independent predictors of clot permeability, while “triple-positivity” predicted lysis time. We conclude that APS is associated with prothrombotic plasma fibrin clot phenotype, with more pronounced abnormalities in arterial thrombosis. Molecular background for this novel prothrombotic mechanism in APS remains to be established.

Keywords

Antiphospholipid syndrome - plasma fibrin clot structure - fibrinolysis

Full Text

References

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