Factor XI deficiency (FXI-Def) is associated with mild, unpredictable bleeding tendency. FXI is believed to participate in a thrombin-dependent positive feed-back that leads to the formation of a second burst of thrombin, which, in turn, inhibits fibrinolysis mainly through TAFI activation. It is conceivable, therefore, that FXI-Def leads to the formation of clots that are more susceptible to lysis. Our study was undertaken to test this hypothesis.

Eighteen subjects with FXI-Def (1-58%), and 17 matched controls were studied. All assays were performed on citrate-plasma stored at -80°C.

The fibrinolytic resistance to t-PA (30 ng/ml) of clots generated by 0.5 pM tissue factor was lower in samples from FXI-Def subjects than in controls (lysis time: 61.1 ± 9.7 vs 74.9 ± 14.9 min, P=0.008). Generation of thrombin and TAFIa during fibrinolysis was markedly reduced in FXI-Def samples (<0.0005) and TAFIa10min was significantly correlated with lysis time (rho=0.56, P=0.01). Furthermore, enhancement of TAFI activation by thrombomodulin increased fibrinolytic resistance to normal. However, neutralization of TAFIa by PTCI did not abolish the difference between the two groups, suggesting that both TAFI-dependent and TAFI-independent mechanisms concurred to enhance the lysability of FXI-Def clots. Several findings suggest that FXI-Def is not the main cause of hastened fibrinolysis: 1) lysis time did not correlate with FXI level; 2) a significant difference in fibrinolytic resistance between FXI-Def and controls was observed under conditions that bypassed FXI activation (clots induced by thrombin+CaCl2+FXa-inhibitor or by a 100-fold higher concentration of tissue factor) or after normalization of FXI levels by addition of purified FXI. In conclusion, bleeding in FXI-Def may result from premature lysis of the haemostatic plug, which ensues because of little TAFI activation and other unidentified mechanisms. Moreover, it appears that FXI-Def is not part of the causal pathway leading to hastened fibrinolysis but rather a bystander.


Peyvandi:NovoNordisk: Research Funding, speaker's fee Other; CSL Behring: speaker's fee, speaker's fee Other; LFB: speker's fee, speker's fee Other; Grifols: speaker's fee, speaker's fee Other; Bayer: speaker's fee Other; Baxter: speaker's fee Other; Biotest: Research Funding; Kedrion biopharma: Research Funding. Colucci:Boehringer Ingelheim : Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.

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