Transbronchial biopsy in the presence of profound elevation of the international normalized ratio

To identify a level of coagulopathy, reported as the international normalized ratio (INR), that predicts hemorrhage following transbronchial forceps biopsy (TBBx) in an animal model.

Crossover blinded study using Yucatan mini-swine (Sus scrofa).

Tertiary medical center with a dedicated animal research facility.

A two-stage study. In stage 1, flexible fiberoptic bronchoscopy with TBBx was performed to establish the amount of bleeding in animals with normal coagulation systems. Animals then were administered escalating dosages of warfarin to obtain one of several increased INR levels. The endpoint of stage 1 was defined as the INR that resulted in a blood loss of > or = 100 mL in > or = 50% of the study animals. In stage 2, all the animals were to be anticoagulated to the INR level determined in stage 1. Topical and systemic measures would then be administered in an attempt to decrease postprocedure hemorrhage, and the results were recorded.

Eighteen animals were enrolled in the study. Despite INR levels > 10, no animals developed a hemorrhagic complication of the transbronchial forceps biopsy (TBBx). Eleven animals had INRs > 7. Four animal deaths were recorded, with three animal deaths attributed to nonpulmonary hemorrhage, each due to a ruptured ovarian cyst. One death was anesthesia related. Stage 2 of the study was not performed due to the extreme INR levels reached in the animals during stage 1 and to the lack of a procedure-related complication.

Our study suggests that INR elevation does not correlate with an increased risk of bleeding following TBBx in this animal model.