This may occur due to the administration of phenytoin with or without extravasation. Since the 1990s the identity of ligands involved in leukocyte extravasation have been studied heavily. Having this knowledge allows for better studies of the effect of drugs on leukocyte extravasation. Other mechanisms include invasion through basement membranes, extravasation, and colonization of distant metastatic sites. Interaction with SP receptors induces vasodilation and allows for plasma extravasation and mastocyte degranulation. Complications related to extravasation are possible with any medication. Vessels feature intimal thickening, fibrinoid necrosis, red blood cell fragmentation, extravasation, thrombosis. The tourniquet should be removed before injecting to prevent extravasation of the medication. Hyaluronidase is also used for extravasation of hyperosmolar solutions. Hyaluronidase is a recommended antidote for vinca alkaloid overdose or extravasation. Mucus extravasation may also be observed. Subendothelial deposits of amyloid may weaken blood vessels and lead to the extravasation of blood. The non-contrast images facilitate the differentiation of active extravasation or acute bleeding from vascular calcifications. Altered barrier function is also implicated in cancer extravasation. However it has also been speculated to aid in extravasation in circulating melanoma cells.