Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.
To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.
Idell
S
S
Department of Medicine, University of Texas Health Center, Tyler 75710.
James
K K
KK
Levin
E G
EG
Schwartz
B S
BS
Manchanda
N
N
Maunder
R J
RJ
Martin
T R
TR
McLarty
J
J
Fair
D S
DS
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D005170:Factor X / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D010960:Plasminogen Activators / Q000032:analysis; D015849:Plasminogen Inactivators; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D000990:Antithrombin III; D005170:Factor X; D005337:Fibrin; D010960:Plasminogen Activators