TY - JOUR
T1 - Thrombin activatable fibrinolysis inhibitor pathway alterations correlate with bleeding phenotype in patients with severe hemophilia A
AU - Semeraro, Fabrizio
AU - Mancuso, Maria E.
AU - Ammollo, Concetta T.
AU - Dirienzo, Lavinia
AU - Vitulli, Antonia
AU - Santagostino, Elena
AU - Tripodi, Armando
AU - Colucci, Mario
PY - 2020
Y1 - 2020
N2 - Background: Patients with severe hemophilia A display varied bleeding phenotypes despite similar factor VIII (FVIII) activity levels. Objective: We investigated different thrombin activatable fibrinolysis inhibitor (TAFI)-related variables in patients with severe hemophilia A and their possible correlation with bleeding tendency. Patients/Methods: Sixty-one patients with severe hemophilia A (FVIII:C <1%], treated on demand, were included. Patients were categorized as mild, moderate, and severe bleeders according to number of bleeds per year (≤2, 3-24, ≥25, respectively). Thirty healthy males served as controls. Clot lysis time was assessed by turbidimetric assay, TAFI activation by two-stage functional assay, and response to TAFIa as the prolongation of fibrinolysis time upon addition of purified TAFIa. Circulating levels of activated TAFI (TAFIa/ai) were measured by specific enzyme-linked immunosorbent assay. Results: As compared to controls, hemophilic patients displayed shorter lysis time, less TAFIa generation, and reduced response to TAFIa, but similar TAFIa/ai levels. Clot lysis time was similar in mild, moderate, and severe bleeders, whereas TAFIa generation and response to TAFIa decreased with the increase in bleeding tendency; moreover, circulating TAFIa/ai levels were highest in severe bleeders. Patients with markedly impaired TAFIa generation or TAFIa response (below median) displayed 3-fold to 4-fold higher bleeding rate and factor consumption than patients whose TAFI-related values approached the control ones. Conclusion: The TAFI pathway impairment correlates with bleeding phenotype in severe hemophilia and may represent a promising tool to stratify the bleeding risk.
AB - Background: Patients with severe hemophilia A display varied bleeding phenotypes despite similar factor VIII (FVIII) activity levels. Objective: We investigated different thrombin activatable fibrinolysis inhibitor (TAFI)-related variables in patients with severe hemophilia A and their possible correlation with bleeding tendency. Patients/Methods: Sixty-one patients with severe hemophilia A (FVIII:C <1%], treated on demand, were included. Patients were categorized as mild, moderate, and severe bleeders according to number of bleeds per year (≤2, 3-24, ≥25, respectively). Thirty healthy males served as controls. Clot lysis time was assessed by turbidimetric assay, TAFI activation by two-stage functional assay, and response to TAFIa as the prolongation of fibrinolysis time upon addition of purified TAFIa. Circulating levels of activated TAFI (TAFIa/ai) were measured by specific enzyme-linked immunosorbent assay. Results: As compared to controls, hemophilic patients displayed shorter lysis time, less TAFIa generation, and reduced response to TAFIa, but similar TAFIa/ai levels. Clot lysis time was similar in mild, moderate, and severe bleeders, whereas TAFIa generation and response to TAFIa decreased with the increase in bleeding tendency; moreover, circulating TAFIa/ai levels were highest in severe bleeders. Patients with markedly impaired TAFIa generation or TAFIa response (below median) displayed 3-fold to 4-fold higher bleeding rate and factor consumption than patients whose TAFI-related values approached the control ones. Conclusion: The TAFI pathway impairment correlates with bleeding phenotype in severe hemophilia and may represent a promising tool to stratify the bleeding risk.
KW - bleeding
KW - CPU
KW - hemophilia A
KW - TAFI
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U2 - 10.1111/jth.14656
DO - 10.1111/jth.14656
M3 - Article
C2 - 31571361
AN - SCOPUS:85074323549
VL - 18
SP - 381
EP - 389
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
SN - 1538-7933
IS - 2
ER -