Fatal Ovarian Hemorrhage Associated With Anticoagulation Therapy in a Yucatan Mini-Pig Following Venous Stent Implantation

Abstract

Swine models are commonly utilized in endovascular research for development of intravascular interventions and medical device development. As part of a pilot study for a venous vascular stent device, a 5-year-old female Yucatan mini-pig underwent bilateral external iliac vein stent placement under general anesthesia. To reduce thrombotic complications by reduction of thrombus formation on wires, sheaths, and catheters, the pig was heparinized with a total of 300 IU/kg of heparin, establishing an activated clotting time (ACT) of 436 s. The ACT had returned to below 200 s by the end of the procedure. To prevent postoperative thrombosis, the pig received an anticoagulation therapy protocol consisting of enoxaparin, clopidogrel, and aspirin. There were no complications during the immediate postoperative period. However, the pig died 4 days after surgery. Necropsy established the cause of death as abdominal exsanguination due to severe, acute, intra-ovarian hemorrhage, most likely related to ovulation. Life-threatening ovarian hemorrhage is occasionally seen in women with congenital or acquired bleeding disorders; to our knowledge this is the first report of fatal ovarian hemorrhage in an animal enrolled in a pre-clinical research trial.

Keywords: animal model; bleed; endovascular; ovary; pre-clinical.

Figure 1

Radiographic image from a venogram performed of the right external iliac vein with the test article (venous stent with polymeric inner valve—arrow) positioned in situ.

Figure 2

Ultrasonographic image of the right external iliac artery with the test article (venous stent with polymeric inner valve—valve is indicated by asterix) positioned in situ. The blood flow was unidirectional.

Figure 3

(A) Post mortem photograph of the left external iliac vein. The venous stents were identified in the right and left (arrow) external iliac veins without associated vessel perforation or thrombi, precluding the stents as the cause of the fatal hemoabdomen. (B) Post mortem photograph of the left ovary. The left ovary was expanded with blood—ovarian hemorrhage was considered to be the source of hemorrhage and thus the cause of death. The right ovary was considered to be normal in size and had pinpoint foci of hemorrhage with histological retention of the normal architecture.