title: Altered plasma fibrin clot properties and fibrinolysis in patients with multiple myeloma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Ex vivo 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 (Ks ), compaction, indicating denser fibrin clots, impaired fibrin polymerization with longer lag phase and lower final turbidity (D-Dmax ), combined with hypofibrinolysis reflected by longer lysis time and slower rate of D-dimer release from fibrin clots (D-Drate ) compared with controls (all P < 0·001).
  
  
  RESULTS
  Patients with IgG MM had lower Ks compared with IgA MM [5·9 (5·1-6·4) vs. 6·3 (5·9-7·2) 10(-9)  cm(2) ; P = 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; P = 0·022]. Of the fibrin variables, only Ks 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(-9)  cm(2) ; P = 0·015]. Multivariate analysis adjusted for age and fibrinogen showed that in MM patients elevated peak thrombin levels determine Ks and D-Dmax , while thrombin-activatable fibrinolysis inhibitor (TAFI) activity predicts Ks , t50% , D-Drate and lag phase.
  
  
  CONCLUSIONS
  Our study demonstrates prothrombotic fibrin clot phenotype in patients with MM, with a significant impact of increased thrombin formation and TAFI activity.
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Lidia
authors.initials: L
authors.lastname: Zubkiewicz-Usnarska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Helbig
authors.forename: Dariusz
authors.initials: D
authors.lastname: Woszczyk
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozińska
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: Maria
authors.initials: M
authors.lastname: Podolak-Dawidziak
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
mesh_terms: D000368:Aged; D005260:Female; D005337:Fibrin / Q000502:physiology*; D063285:Fibrin Clot Lysis Time; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood*; D010641:Phenotype; D013917:Thrombin / Q000378:metabolism / Q000502:physiology
chemical_list: D005337:Fibrin; D013917:Thrombin
keywords: Fibrin clot; fibrinolysis; multiple myeloma; thrombin