PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder of unknown etiology. It is estimated that IPF afflicts upwards of 100,000 people in the US, but it has no known effective treatment short of lung transplantation. Several lines of evidence link the blood coagulation system to the abnormal wound healing process that leads to tissue scarification. In addition, two large cohort studies demonstrate an epidemiological association between systemic vascular thrombosis and IPF. We hypothesize that inherited/acquired thrombophilic states predispose patients to pulmonary fibrosis.
METHODS: In this cross-sectional study, patients were enrolled from the population referred to the Pulmonary Clinic of the University of Chicago. Inclusion criteria: diagnosis of IPF according to the ATS/ERS diagnostic consensus statement. Coagulation assays and pulmonary function tests were performed using standard techniques. We used unpaired student’s t-test or Mann Whitney U test to compare continuous variables, and Fisher’s exact test to compare proportional values.
RESULTS: We identified 133 IPF patients. Their age (mean 67.2 years, SD 9.04), gender (male 67.7%), and disease severity (mean FVC 64.2% of predicted, SD 17.8; mean DLCO 47.5% of predicted, SD 18.3) were consistent with that of prior large IPF cohort studies. Compared to historical controls, our IPF patients had a 5-fold increase in the prevalence of functional protein C deficiency (0.2% in historical controls versus 0.98% in the present study), a 6-fold increase in the prevalence of functional protein S deficiency (0.3% versus 1.88%), and a 215-fold increase in the prevalence of antithrombin III deficiency (0.02% versus 4.3%). Furthermore, low levels of anti-coagulant proteins in the blood correlated with a low DLCO.
CONCLUSIONS: (1) IPF was associated with a higher prevalence of thrombophilic states; (2) low levels of anti-coagulant proteins in the blood correlated with a low DLCO.
CLINICAL IMPLICATIONS: (1) Inherited/acquired tendency to thrombose may underlie the pathogenesis of IPF; (2) Studies are needed to determine if treatment with anti-coagulants will improve the prognosis of IPF patients.
DISCLOSURE: The following authors have nothing to disclose: Manuel Ribeiro Neto, Imre Noth, Amanda Hardy, Amy Castilano, Jennifer Leising, Mitchell Olman
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