The goal of this clinical trial is to learn if apixaban (a pill) is a safe and easier alternative to taking enoxaparin (a daily shot) to prevent blood clots after head and neck cancer surgery. It will also learn about side effects of both medicines.

The main questions it aims to answer are:

Can apixaban be used safely instead of enoxaparin to prevent blood clots after surgery? Do patients find apixaban easier or more satisfying to take than enoxaparin? How well do patients follow the treatment plan with each medicine?

Researchers will compare 2 groups:

One group will take apixaban (a pill taken twice a day) for 10 days after surgery.

The other group will take enoxaparin (a shot given once a day) for 10 days after surgery.

Participants will:

Take either apixaban or enoxaparin starting 12-24 hours after surgery, for 10 days total Keep a medication diary and bring back unused medicine so the study team can check adherence Complete short surveys about satisfaction with their medicine Have an ultrasound of their legs to check for blood clots 11-14 days after surgery Return for follow-up visits about 40 days and 80 days after surgery for safety checks

How long will participation last? About 4 months from surgery through the last follow-up visit.

Inclusion Criteria:

Participants must:

• Provide signed and dated informed consent.
• Be willing and able to comply with study procedures and follow-up.
• Be 18-89 years old (male or female).
• Have a negative pregnancy test within 24 hours before surgery (if woman of childbearing potential).
• Have biopsy-proven head and neck cancer, or a suspected cancer awaiting tissue diagnosis (can be confirmed by frozen section at surgery).
• Be scheduled for major inpatient or outpatient oncologic head and neck surgery (defined as >45 minutes operative time).
• Be an appropriate surgical candidate (adequate performance status).

Eligible diagnoses include (not limited to):

• Squamous cell carcinoma of oral cavity, hypopharynx, larynx, nasal cavity
• Malignancies from major salivary glands
• Non-melanoma skin cancers (squamous cell, basal cell, Merkel cell carcinoma)
• Unknown primary tumors of head and neck

Exclusion Criteria:

Participants cannot:

• Lack a tissue diagnosis of head and neck cancer during the study period.
• Have one of these conditions instead of eligible cancer: Benign disease; Primary thyroid cancer (lower VTE risk); Lymphoma (not primarily surgical); or Melanoma
• Fail to undergo definitive head and neck oncologic surgery (e.g., only diagnostic biopsy).
• Have surgery limited to tissue diagnosis only (e.g., direct laryngoscopy, excisional lymph node biopsy).
• Be unable (patient or caregiver) to administer the study drug.
• Have a positive pregnancy test on the day of surgery.
• Have a known history of prior DVT or PE (since extended anticoagulation would be indicated).
• Have hereditary or acquired bleeding/clotting disorders.
• Have severe renal impairment (CrCl <30 mL/min).
• Have conditions that, in the investigator's judgment, make study participation unsafe or confound results.