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Thromboembolic disease prevention before cancer therapy


KEY POINTS

  • Patients with cancer account for more than 20% of all newly diagnosed cases of venous thromboembolic events (VTEs); they are six times more likely to develop VTEs

  • Risk factors for VTE in patients with cancer are patient-, cancer-, and treatment-related

  • As one single risk factor does not reliably predict risk, risk assessment models have been developed, such as the Khorana Risk Score

  • Patients with cancer who have a Khorana Risk Score of 3 or greater who are undergoing low-molecular-weight heparin (LMWH) therapy or 2 or greater undergoing direct oral anticoagulant (DOAC) experience a 60% reduction in VTE and/or VTE-related deaths

  • American Society of Clinical Oncology (ASCO), International Society on Thrombosis and Hemostasis (ISTH), and International Initiative on Thrombosis and Cancer (ITAC) guidelines suggest the use of DOACs as primary thromboprophylaxis in ambulatory patients with cancer starting chemotherapy with a Khorana score of 2 or greater, in patients with no drug-drug interactions and not at high risk for bleeding

  • LMWH remains an option for outpatient thromboprophylaxis in patients at high risk

  • Patients with multiple myeloma receiving immunomodulatory drugs (IMiD)-based combination therapy, current guidelines recommend aspirin 81 to 325 mg daily if none or only one individual/myeloma risk factor, otherwise LMWH equivalent to 40 mg enoxaparin daily or full-dose warfarin

  • In hospitalized patients with major surgery or acute medical illness, thromboprophylaxis with heparin or LMWH is recommended per standard recommendations with consideration for 4 weeks extension postoperatively in patients at high risk in the setting of abdominal and pelvic surgery for malignancy

Thromboembolic events can manifest either synchronously or metachronously in the course of a malignancy and can involve both the venous and arterial systems. Venous thromboembolism (VTE) includes deep-vein thrombosis (DVT), visceral vein thrombosis, and pulmonary embolism (PE), and is much more prevalent. Compared with the general population, patients with cancer are six times more likely to develop VTE and they account for more than 20% of all newly diagnosed cases of VTE. Arterial events, such as stroke and myocardial infarction, are also more common in patients with cancer than in the general population (as reviewed in Chapter 8 ).

Thrombosis is often associated with detrimental effects in patients with cancer. VTE can complicate postoperative recovery, medical hospitalization, and systemic chemotherapy and increase the cost of cancer treatments and hospitalizations. A strong association exists of VTE with short- and long-term mortality, and thromboembolism is the second-leading cause of death among outpatients with cancer after cancer itself. Therapeutic anticoagulation carries a substantial risk for both serious bleeding complications and recurrence of VTE in patients with cancer. Indeed, one in four patients with cancer-associated VTE require readmission owing to bleeding or VTE recurrence. Therefore, appropriate prevention of thrombosis is important to reduce its impact on patients on patients with cancer and on the health system in general. This chapter provides an overview of risk stratification approaches and prevention of VTE in patients with cancer. Chapters 18 and 30 will cover the management of incident and recurrent VTE.

Risk factors for cancer-associated VTE

Risk factors for VTE in patients with cancer can be considered in three main categories: patient, cancer, and treatment-related ( Table 9.1 ).

  • Patient-related risk factors include advanced age, black race, and associated comorbidities such as obesity, infection, anemia, and renal and pulmonary disease.

  • Cancer-related risk factors: The risk for VTE also varies according to the primary site and histologic subtype of the cancer. Patients with advanced malignancies and primary brain tumors, pancreatic, stomach, and lung cancers have the highest risk ( Fig. 9.1 ). In hematologic malignancies, patients with lymphoma are also at increased risk for VTE. The natural history of the cancer itself is another risk factor, in which, the greatest risk for VTE has been shown in the first 3 months of initial diagnosis.

    FIG. 9.1, Two-year cumulative incidence (%) of venous thromboembolism (VTE) per type and stage of cancer. Types of cancer were ordered by their respective 1-year mortality rates.

  • Treatment-related risk factors: Risk for cancer-associated thrombosis increases with the use of systemic chemotherapy, usually by two- to six-fold. Long-term use of central catheters has also been found to increase the risk for VTE in patients with cancer. Antiangiogenic agents, such as bevacizumab, increase the risk for both arterial and venous events. Thalidomide and lenalidomide also increase the risk for VTE in patients with multiple myeloma when combined with dexamethasone. In addition to systemic chemotherapy, other supportive therapies, including the use of erythropoiesis stimulating agents, red blood cell and platelet transfusions, further increase the risk for VTE.

TABLE 9.1
Risk Factors for Venous Thromboembolism in Patients with Cancer
VARIABLES RISK FACTORS
Patient-related Advanced age
Ethnicity (higher in Blacks)
Comorbidities (obesity, infection, anemia, renal, and pulmonary disease)
Cancer-related Primary site of cancer
Histologic subtype
Natural history of cancer
Treatment-related Indwelling catheters
Systemic chemotherapy
Supportive therapies (e.g., erythropoiesis-stimulating agents; red blood cell and platelet transfusion)
VTE , Venous thromboembolism.

Cancer-associated arterial thromboembolism

Patients with cancer also face an increased short-term risk of arterial thromboembolic events, including myocardial infarction and stroke. In a recent study, compared with patients without cancer, the 6-month cumulative incidence of arterial thromboembolism (4.7% vs. 2.2%), myocardial infarction (2% vs. 0.7%), and ischemic stroke (3% vs. 1.6%) was significantly higher in patients with cancer. Arterial events are frequently occurring complications during cancer therapies, mainly attributed to the toxicity profiles of vascular endothelial growth factor (VEGF) antagonists, such as bevacizumab, sunitinib, and sorafenib. Such agents can induce endothelial dysfunction with a decrease in the levels of nitric oxide and prostacyclin, thereby leading to platelet activation. These mechanisms might stir up a downstream cascade of events in patients with preexisting coronary and cerebral artery diseases to promote thrombosis. As mentioned previously, an increased risk of arterial thromboembolic events also exists in patients with multiple myeloma who are treated with lenalidomide.

Compared with VTE, there is a paucity of information regarding risk factors and prevention of cancer-associated arterial thromboembolism. Further discussion in this chapter is primarily focused on the prevention of venous events, prevention of arterial events is covered in Chapter 8 .

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