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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

Magdalena Celińska-Löwenhoff
1   Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
,
Teresa Iwaniec
1   Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
,
Agnieszka Padjas
1   Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
,
Jacek Musiał
1   Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
,
Anetta Undas
2   Institute of Cardiology Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland
› Author Affiliations Financial support: This work was supported by Jagiellonian University Medical College (grant no. K/ZDS/002936 to A.U) and National Science Center (grant no. UMO-2011/03/B/NZ6/01608 to J.M).
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Publication History

Received: 26 November 2013

Accepted after major revision: 26 February 2014

Publication Date:
04 December 2017 (online)

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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
 

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