Inclusion Criteria:
* Active malignancy defined as histologically confirmed diagnosis within last 6 months or received any cancer directed therapy within the last 6 months.
* Radiologically confirmed newly diagnosed symptomatic deep vein thrombosis or pulmonary embolism within 28 days of enrollment. Includes proximal lower-limb DVT or symptomatic PE. Upper extremity or catheter-associated thrombosis will be included, as will distal lower extremity DVTs.
* Platelet count \< 75,000/ml (prior to platelet transfusion) within 28 days of VTE diagnosis.
* Platelet count responsive to transfusion if previously administered (defined as an average platelet increase of at least 10,000/ml over the last 3 transfusions.
* No evidence of active hemorrhage.
* No recent history of major hemorrhage (requiring transfusion, hospitalization or intervention) within the last 12 months.
* No known brain metastases.
* Age ≥18 years. Because no dosing or adverse event data are currently available on the use of apixaban in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
* ECOG performance status ≤2
* Participants must have adequate organ and marrow function as defined below:
* Total bilirubin ≤ institutional upper limit of normal (ULN)
* AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
* Glomerular filtration rate (GFR) ≥25 mL/min/1.73/m2
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* The effects of apixaban on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of apixaban administration.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Participants who are receiving any other investigational agents.
* Participants who have had a thrombectomy, insertion of a caval filter, or require a fibrinolytic agent.
* Participants that have index events with severe clot burden defined as bilateral proximal lower extremity deep vein thrombosis and saddle embolism or pulmonary embolism with hemodynamic compromise.
* Participants with acute myeloid leukemia or myelodysplastic syndrome or who are undergoing or have undergone allogeneic stem cell transplant.
* Participants with luminal gastrointestinal malignancy or genitourinary cancer.
* Presence of known or prior brain metastasis, given the increased risk of life-threatening intracranial hemorrhage with anticoagulant use. While screening for brain metastases is not standard of care in this population, investigators may obtain brain imaging if clinically indicated prior to initiation of anticoagulation. Imaging is not mandated in order to participate in this study.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to apixaban.
* Participants receiving any medications or substances that are inhibitors or inducers of CYP3A/P-gp are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
* Participants on aspirin (\>100 mg/day), dual antiplatelet therapy, or receiving chronic treatment with NSAIDS
* Participants with uncontrolled intercurrent illness.
* Participants at high risk of bleeding such as:
* Unresected luminal/mucosal GI and GU cancers
* Active gastric or duodenal cancer
* History of major bleeding (based on ISTH criteria) in the past 12 months
* Any prior history of Intracranial hemorrhage (microhemorrhage is not included)
* Clinical or laboratory concern for ongoing DIC (prolonged PT/APTT or low fibrinogen)
* Severe renal disease (CKD Stage IV or higher) or liver disease (Child Pugh B/C)
* Participants with pre-planned major surgery within the study period
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because apixaban has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with apixaban, breastfeeding should be discontinued if the mother is treated with apixaban.
* Participant must be able to swallow pills.
