Altered plasma fibrin clot properties and fibrinolysis in patients with multiple myeloma. (June 2014)

• Record Type: Journal Article
• Authors: Undas, Anetta; Zubkiewicz‐Usnarska, Lidia; Helbig, Grzegorz; Woszczyk, Dariusz; Kozińska, Justyna; Dmoszyńska, Anna; Podolak‐Dawidziak, Maria; Kuliczkowski, Kazimierz
• Is Part Of: European journal of clinical investigation. Volume 44:Number 6(2014:Jun.)
• Page Start: 557
• Page End: 566
• Publication Date: 2014-06
• Subjects: Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12269
• Languages: English
• ISSNs: 0014-2972

Abstract

<abstract abstract-type="main" id="eci12269-abs-0001"> <title>Abstract</title> <sec id="eci12269-sec-0001" sec-type="section"> <title>Background</title> <p>Multiple myeloma (MM) is associated with increased risk of venous and arterial thromboembolism. Formation of denser and poorly lysable fibrin clots is observed in patients with arterial and venous thromboembolism. We investigated fibrin clot properties and their determinants in MM patients.</p> </sec> <sec id="eci12269-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p> <italic>Ex vivo</italic> plasma fibrin clot permeability, turbidity and susceptibility to lysis were evaluated in 106 MM patients at the time of diagnosis vs. 100 age‐ and sex‐matched controls. MM patients had lower clot permeability (<italic>K</italic><sub>s</sub>), compaction, indicating denser fibrin clots, impaired fibrin polymerization with longer lag phase and lower final turbidity (<italic>D</italic>−<italic>D</italic><sub>max</sub>), combined with hypofibrinolysis reflected by longer lysis time and slower rate of D‐dimer release from fibrin clots (<italic>D</italic>−<italic>D</italic><sub>rate</sub>) compared with controls (all <italic>P </italic>< 0·001).</p> </sec> <sec id="eci12269-sec-0003" sec-type="section"> <title>Results</title> <p>Patients with IgG MM had lower <italic>K</italic><sub>s</sub> compared with IgA MM [5·9 (5·1–6·4) vs. 6·3 (5·9–7·2) 10<sup>−9</sup> cm<sup>2</sup>; <italic>P </italic>= 0·007] and longer lysis time compared with light‐chain‐disease patients [11·4 (10·9–12·3) vs. 10·7 (9·8–11·9) min; <italic>P </italic>= 0·022]. Of the fibrin variables, only <italic>K</italic><sub>s</sub> was significantly lower in patients with International Staging System (ISS) grade III than in those with ISS grade I and II [5·9 (4·9–6·6) vs. 6·2 (5·7–6·8) 10<sup>−9</sup> cm<sup>2</sup>; <italic>P </italic>= 0·015]. Multivariate analysis adjusted for age and fibrinogen showed that in MM patients elevated peak thrombin levels determine <italic>K</italic><sub>s</sub> and <italic>D</italic>−<italic>D</italic><sub>max</sub>, while thrombin‐activatable fibrinolysis inhibitor (TAFI) activity predicts <italic>K</italic><sub>s</sub>, <italic>t</italic><sub>50%</sub>, <italic>D</italic>−<italic>D</italic><sub>rate</sub> and lag phase.</p> </sec> <sec id="eci12269-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our study demonstrates prothrombotic fibrin clot phenotype in patients with MM, with a significant impact of increased thrombin formation and TAFI activity.</p> </sec> </abstract>