ASCO has released a new evidence-based clinical practice guideline for venous thromboembolism prophylaxis and treatment, updating the 2007 practice guideline.¹ The update is based on a systematic review of literature published from December 2007 to December 2012. An Update Committee reviewed evidence to determine which of the prior recommendations required revision.  The update provides recommendations about six clinical questions, as summarized below.

Six Questions

Should hospitalized patients with cancer receive anticoagulation for venous thromboembolism prophylaxis?

• Those who have active malignancy with acute medical illness or reduced mobility should receive pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications.
• Those who have active malignancy without additional risk factors may be considered for pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications.
• Data are inadequate to support routine thromboprophylaxis in patients admitted for minor procedures or short chemotherapy infusion, or in patients undergoing stem cell/bone marrow transplantation.

Should ambulatory patients with cancer receive anticoagulation for venous thromboembolism prophylaxis during systemic chemotherapy?

• Routine pharmacologic thromboprophylaxis is not recommended in cancer outpatients.
• Based on limited randomized controlled trial data, clinicians may consider low–molecular-weight heparin prophylaxis on a case-by-case basis in highly selected outpatients with solid tumors receiving chemotherapy. Consideration of such therapy should be accompanied by a discussion with the patient about the uncertainty concerning benefits and harms, as well as dose and duration of prophylaxis in this setting.
• Patients with multiple myeloma receiving thalidomide (Thalomid)- or lenalidomide (Revlimid)-based regimens with chemotherapy and/or dexamethasone should receive pharmacologic thromboprophylaxis with either aspirin or low–molecular-weight heparin for lower-risk patients and low–molecular-weight heparin for higher-risk patients.

Should patients with cancer undergoing surgery receive perioperative venous thromboembolism prophylaxis?

• All patients with malignant disease undergoing major surgical intervention should be considered for pharmacologic thromboprophylaxis with either unfractionated heparin or low–molecular-weight heparin unless contraindicated because of active bleeding or high bleeding risk.
• Prophylaxis should be commenced preoperatively.
• Mechanical methods may be added to pharmacologic thromboprophylaxis but should not be used as monotherapy for venous thromboembolism prevention unless pharmacologic methods are contraindicated because of active bleeding or high bleeding risk.
• A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients.
• Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least 7 to 10 days. Extended prophylaxis with low–molecular-weight heparin for up to 4 weeks postoperatively should be considered for patients undergoing major abdominal or pelvic surgery who have such high-risk features as restricted mobility, obesity, history of venous thromboembolism, or additional risk factors (specified in full guideline). In lower-risk surgical settings, the decision on appropriate duration of thromboprophylaxis should be made on a case-by-case 
• basis considering the individual patient.

What is the best method for treatment of patients with cancer with established venous thromboembolism to prevent recurrence?

• Low–molecular-weight heparin is preferred over unfractionated heparin for the initial 5 to 10 days of anticoagulation for the patient with cancer and newly diagnosed venous thromboembolism who does not have severe renal impairment (defined as creatinine clearance < 30 mL/min).
• For long-term anticoagulation, low–molecular-weight heparin for at least 6 months is preferred due to improved efficacy over vitamin K antagonists. Vitamin K antagonists are an acceptable alternative for long-term therapy if low–molecular-weight heparin is not available.
• Anticoagulation with low–molecular-weight heparin or vitamin K antagonists beyond the initial 6 months may be considered for select patients with active cancer, such as those with metastatic disease or those receiving chemotherapy.
• The insertion of a vena cava filter is indicated only for patients with contraindications to anticoagulant therapy (specified in full guideline). It may be considered as an adjunct to anticoagulation in patients with progression of thrombosis (recurrent venous thromboembolism or extension of existing thrombus) despite optimal therapy with low–molecular-weight heparin.
• For patients with primary central nervous system malignancies, anticoagulation is recommended for established venous thromboembolism as for other patients with cancer. Careful monitoring is necessary to limit risk of hemorrhagic complications.
• Use of novel oral anticoagulants for either prevention or treatment of venous thromboembolism in patients with cancer is not recommended at this time.
• Based on panel consensus, incidental pulmonary embolism and deep-vein thrombosis should be treated in the same manner as symptomatic venous thromboembolism. Treatment of splanchnic or visceral vein thrombi diagnosed incidentally should be considered on a case-by-case basis, considering potential benefits and risks of anticoagulation.

Should patients with cancer receive anticoagulants in the absence of established venous thromboembolism to improve survival?

• Anticoagulants are not recommended to improve survival in patients with cancer without venous thromboembolism.
• Patients with cancer should be encouraged to participate in clinical trials designed to evaluate anticoagulant therapy as an adjunct to standard anticancer therapies.

What is known about risk prediction and awareness of venous thromboembolism amongst patients with cancer?

• Based on panel consensus, it is recommended that patients with cancer should be assessed for venous thromboembolism risk at the time of chemotherapy initiation and periodically thereafter. Individual risk factors, including biomarkers or cancer site, do not reliably identify patients with cancer at high risk of venous thromboembolism. In the outpatient setting, risk assessment can be conducted based on a validated risk assessment tool (see commentary here).
• Based on panel consensus, it is recommended that oncologists educate patients regarding venous thromboembolism, particularly in settings that increase risk such as major surgery, hospitalization, and systemic antineoplastic therapy.

Patient and Clinician Communication

The panel emphasizes that patients are “woefully” unaware of the risk for and warning signs and symptoms of venous thromboembolism, despite the well-known association of venous thromboembolism and cancer. As stated by the authors, “Communicating with patients about both the signs and symptoms and risk of [venous thromboembolism] events is crucial. Oncologists, along with other healthcare professionals on the oncology team, should assure, at minimum, that patients have a basic recognition of [venous thromboembolism] warning signs.”

Health Disparities

The panel states that rates of venous thromboembolism are higher among African Americans than among the rest of the general population. The panel also notes that minority racial/ethnic patients with cancer suffer disproportionately from comorbidities, have more substantial obstacles to receiving care, are more likely to be uninsured, and are at greater risk of receiving poor quality care than other Americans.

As stated by the authors, “Awareness of … disparities in access to care should be considered in the context of this clinical practice guideline and health care providers should strive to deliver the highest level of cancer care to these vulnerable populations.” ■

Disclosure: For full disclosures of the study authors visit JCO.ASCOPubs.org.

Reference

1. Lyman GH, Khorana AA, Kuderer NM, et al: Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 31:2189-2204, 2013.