Fibrin resistance to lysis in patients with pulmonary hypertension other than thromboembolic.
BACKGROUND
Reportedly, fibrin isolated from patients with chronic thromboembolic pulmonary hypertension (CTEPH) is resistant to lysis. Persistence of regions within the fibrin beta chain, which mediate cell signaling and migration, could trigger the organization of pulmonary thromboemboli into chronic intravascular scars.


OBJECTIVE
Ascertain whether fibrin resistance to lysis occurs in patients with pulmonary hypertension (PAH) other than CTEPH, and in those with prior pulmonary embolism (PE) and no pulmonary hypertension.


METHODS
Fibrinogen was purified from 96 subjects (17 with CTEPH, 14 with PAH, 39 with prior PE, and 26 healthy control subjects) and exposed to thrombin to obtain fibrin clots. Plasmin-mediated cleavage of fibrin beta chain was assessed hourly over a 6-hour period by polyacrylamide gel electrophoresis. Fibrin band intensity was measured by densitometry of stained gels. Data were normalized to the band intensity of the undigested protein.


RESULTS
By 1 hour of digestion, fibrin band intensity had decreased by a median of 25% (interquartile range [IQR], 20 to 27%) in control subjects, and by 15% (IQR, 11 to 18%) in patients with prior PE (P < 0.0001). The 1-hour median reduction in band intensity was 2% (IQR, 1 to 3%) in CTEPH, and 4% (IQR, 2 to 7%) in PAH (P < 0.0001 vs. control subjects and PE). The decline in fibrin band intensity remained significantly different among the four groups up to 6 hours (P < 0.0001).


CONCLUSIONS
Fibrin resistance to lysis occurs in pulmonary hypertension other than CTEPH and, to a smaller extent, in patients with prior PE and no pulmonary hypertension.
Miniati
Massimo
M
Dipartimento di Area Critica Medico Chirugica, Università di Firenze, Viale Morgagni 85, 50134 Florence, Italy. massimo.miniati@unifi.it
Fiorillo
Claudia
C
Becatti
Matteo
M
Monti
Simonetta
S
Bottai
Matteo
M
Marini
Carlo
C
Grifoni
Elisa
E
Formichi
Bruno
B
Bauleo
Carolina
C
Arcangeli
Chiara
C
Poli
Daniela
D
Nassi
Paolo Antonio
PA
Abbate
Rosanna
R
Prisco
Domenico
D
D000328:Adult; D001797:Blood Protein Electrophoresis; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005337:Fibrin / Q000502:physiology*; D005342:Fibrinolysis; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000097:blood
D005337:Fibrin