Abstract
Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is due to incomplete reperfusion and remodeling of the pulmonary vessels. Impaired fibrinolysis and residual fibrin persistence may be involved. 5 fibrinogen (F) mutants have been associated with CTEPH.
Aim: To evaluate the correlation between F genotype and resistance to fibrinolysis as measured by a global fibrinolysis assay in CTEPH.
Methods: 8 CTEPH, 16 controls and 2 dysfibrinogenemic (dF) patients with known fibrinolysis resistance were included. The plasma fibrinolytic potential of a tissue-factor triggered clot at two concentrations of t-PA (400 or 200 ng/mL) was assessed by the clot lysis time (CTL), defined as the time needed when the maximum OD is reduced to its 50 % level. All the exons and intron-exon junctions of the F genes were amplified by PCR and sequenced.
Results: The mean CLT was of 9.8 (7.5-12), 9.4 (7.5-11), 9.8 (7-13) and 15 (14-16) min with 400 ng/mL of t-PA and of 33.3 (26-37), 31 (28-35.5), 29.6 (16.5-36) and 43 (39-47) min with 200 ng/mL of t-PA in CTEPH, healthy, anticoagulated controls and dF patients, respectively. 2 CTEPH patients had a resistance to fibrinolysis at both t-PA concentrations compared to controls. None of the reported mutations associated with CTEPH were found. Analysis is ongoing to identify other mutations, if any. PAI and α-2 antiplasmin were in normal range for all patients
Conclusion: 2 patients with CTEPH showed an impaired fibrinolysis as defined by the CTL. No F mutant was identified so far, suggesting that the impaired fibrinolysis is not secondary to an abnormal structure of the F/fibrin. A larger study is needed to confirm if hypofibrinolysis could be involved in CTEPH.
- Copyright ©ERS 2015