Abstract 3331

Hypercoagulability reflected by enhanced activity of clotting factors or a natural inhibitor deficiency is a risk factor of venous thromboembolism (VTE). Whether defects in the fibrinolytic system confer an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic system activity (reflected by clot lysis time [CLT]) and the risk of recurrent VTE.

We followed 704 patients (378 women; mean age 48 years) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, female hormone use, homozygosity or double heterozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. The fibrinolytic potential was assessed using a plasma based clot-lysis assay according to Lisman et al. (1). A tissue factor-induced clot was lysed by adding tissue-type plasminogen activator and the optical density was measured at 405 nm in an absorbance microplate reader every 30 seconds in order to get a clot-lysis turbidity profile. Study end point was symptomatic recurrent VTE.

135 (19%) patients had recurrent VTE. Recurrence was unprovoked in 117 patients and was more frequent in men (97/326, 29.8%) than in women (38/378, 10.1%). When CLT was entered as continuous variable in a Cox proportional hazards model, hazard ratio (HR) for recurrence was 1.13 (95% CI 1.02–1.25; p=0.02) for each 10 minutes prolongation. The HR for recurrence was 1.11 (95% CI 1.11–1.24; p=0.046) after adjustment for age and 1.08 (95% CI 0.98–1.20; p=0.13) after additional adjustment for sex. After 5 years, the likelihood of recurrence was 23.8% (95% CI 19.3%-28.3%) in patients with a CLT longer than 63.5 minutes (25th percentile) as compared with 14.1% (95% CI 7.4%-20.8%; p=0.04) among those with a shorter CLT. Men and women differed with regard to CLT (76.1±16.2 vs. 71.5±13.6 sec, p<0.001). After adjustment for age, the HR was 1.04 (95% CI 0.92–1.18; p=0.54) among men and 1.14 (95% CI 0.93–1.14; p=0.22) among women.

Hypofibrinolysis confers an increased risk of recurrent VTE. The effect was more pronounced in women than in men.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
prospective studies, venous thromboembolism, fibrinolytic agents, thrombolytic therapy, anticoagulation, alteplase, antiphospholipid syndrome, blood coagulation factors, cancer, factor v leiden

1)

Lisman. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood, 2005 105: 1102–5.

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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