Chest
Volume 115, Issue 6, June 1999, Pages 1667-1671
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Laboratory and Animal Investigations
Transbronchial Biopsy in the Presence of Profound Elevation of the International Normalized Ratio

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Study objective

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.

Design

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

Setting

Tertiary medical center with a dedicated animal research facility.

Study design

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≥ 100 mL in ≥ 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.

Results

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.

Conclusions

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

Section snippets

Study Design

The Yucatan mini-swine (Sus scrofa) was selected for the study based on its chest shape, its size, and the similarity of its pulmonary vascular system to that of humans. Previous anticoagulation studies using warfarin have been used in this animal model, and the swine's coagulation system has been demonstrated to be similar to that of humans.

The study was planned as a two-stage crossover study with animals serving as their own controls. In the first stage, the goal was to determine an INR level

Results

Eighteen animals were enrolled in the study. Despite extreme elevations in INR levels (> 7) in 11 animals, no animals developed a hemorrhagic complication due to TBBx (Table 3). Stage 1 of the study was discontinued when no significant hemorrhaging was noted. Stage 2 of the study was not performed due to the failure to identify an INR level that indicated a significant risk of hemorrhage following TBBx. Three animals had an INR between 5 and 6. Four animals died during the study. The death of

Discussion

The Yucatan mini-swine was chosen for this study for the following reasons: (1) the size of the animal allowed intubation with a 7.5-mm endotracheal tube that would accommodate a bronchoscope with a channel diameter sufficient to allow the use of 2.2-mm biopsy forceps; (2) the shape and size of the animal approximated that of a small adult patient; (3) the previous use of this animal in cardiac stent and anticoagulation studies; and (4) similarities between swine and human coagulation systems.12

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    For editorial comment see page 1492.

    Financial support was given through the office of the United State Air Force Surgeon General and was distributed through the Clinical Investigation Facility at Wilford Hall Medical Center.

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