While Karen was attempting to cure an extremely burned patient, the patient awoke and turned out to be a vampire, biting both her and her colleague Curtis Webb. In that very moment, Blade arrives to finish the vampire, who manages to escape, and he was intended to kill her as well, but she reminded him of his mother, and he decided to save her. Blade brings Karen to his base, where Whistler complains about his decision.
When Karen wakes up, Whistler acknowledges her on the existence of vampires and on their mission of vampire hunters, telling her of Blade's past too. Karen decides to come back home, and Whistler gives her a spray charged with garlic and silver. Blade warns her that she'll become a vampire too, and she decides to start a research on a possible cure.
Once at home, Karen is attacked by Officer Krieger, one of Deacon Frost's familiars. She's saved by Blade, and complains about being used as a bait. She decides to be at Blade's side, both for personal security and for getting through the situation, and the two follows Krieger to a Frost's club. In here, they find out the Deacon's plan regarding La Magra, the Vampire God, and confront the obese vampire Pearl. Karen, disgusted by the vampire, kills him with a UVA torch when he has told them all the informations they needed.
Blade and Karen are then attacked by Mercury, one of Frost's lovers and generals, and her minions, but they manage to escape thanks to Whistler's arrival. Once at the base, Karen, starting from her own corrupted blood, finds a cure, and injects herself with it, healing from the infection. A short time later, Deacon Frost himself attacks the base and kidnaps her, after torturing Whistler. She's used by Frost as a bait for Blade, who sees a videotape in which she asks for help.
In Frost's base, Karen mocks him about his human origins, and tells him about her discoveries on vampire transformation, which is caused by something similar to a virus. She tells him about the cure she found, too, claiming that she doesn't care if he bites her, since she can cure herself.
When Blade is captured, Karen is brought to the temple of La Magra and thrown in a pit, where she finds Curtis Webb, who has become a ghoul. She fights him and manages to escape using the human bones found at the bottom of the pit. She goes to Blade and frees him from the iron maiden in which he was held, but she's attacked by Vanessa. After Blade kills the vampire, Karen offers her blood to him, so he can regain his strength to fight Frost. Blade nearly drains Karen of her blood but he stops himself in time. During the fight, Karen is attacked by Mercury, but she manages to kill her with Whistler's spray.
After Frost's death, when it's all over, Karen offers Blade her cure, but he refuses, wanting to preserve his powers in order to keep fighting the vampires.