What is the relationship between cancer and the risk of developing pulmonary embolism (PE)?

From the Guidelines

Cancer significantly increases the risk of developing pulmonary embolism (PE) due to its hypercoagulable state, with certain types like pancreatic, brain, and ovarian cancer carrying a higher risk. The relationship between cancer and PE is complex, involving the release of procoagulant substances, inflammatory cytokines, and microparticles that activate the coagulation cascade and promote blood clot formation 1. Cancer treatments such as chemotherapy, hormone therapy, and surgery further increase thrombotic risk, while decreased mobility due to illness or hospitalization leads to blood stasis in the veins 1.

Key Factors Influencing PE Risk in Cancer Patients

• The overall risk of venous thromboembolism in cancer patients is four times as great as in the general population 1
• Certain cancer types, such as multiple myeloma, brain, and pancreatic cancer, have a higher relative risk for VTE 1
• Patients receiving chemotherapy have a six-fold increase in the adjusted risk ratio for VTE compared with a healthy population 1
• The presence of metastatic disease substantially increases PE risk compared to localized cancer 1

Management of PE in Cancer Patients

• Prophylactic anticoagulation with low molecular weight heparin (such as enoxaparin 40mg daily) is often recommended during hospitalization or in high-risk outpatient settings 1
• Cancer-associated PE typically requires therapeutic anticoagulation for at least 3-6 months, with direct oral anticoagulants (DOACs) like apixaban or rivaroxaban now considered appropriate options for many cancer patients 1
• The choice between LMWH and edoxaban or rivaroxaban is left to the discretion of the physician, and the patient’s preference, with consideration of the success of anticancer therapy, the estimated risk of recurrence of VTE, the bleeding risk, and the preference of the patient 1

From the FDA Drug Label

In the EINSTEIN DVT and EINSTEIN PE studies, 49% of patients had an idiopathic DVT/PE at baseline Other risk factors included previous episode of DVT/PE (19%), recent surgery or trauma (18%), immobilization (16%), use of estrogen-containing drug (8%), known thrombophilic conditions (6%), or active cancer (5%) Approximately 90% of patients enrolled in AMPLIFY had an unprovoked DVT or PE at baseline. The remaining 10% of patients with a provoked DVT or PE were required to have an additional ongoing risk factor in order to be randomized, which included previous episode of DVT or PE, immobilization, history of cancer, active cancer, and known prothrombotic genotype

The relationship between cancer and the risk of developing pulmonary embolism (PE) is that cancer is a risk factor for developing PE.

• Active cancer was present in 5% of patients in the EINSTEIN DVT and EINSTEIN PE studies.
• History of cancer and active cancer were also listed as risk factors for recurrence in the AMPLIFY study. However, the exact nature of this relationship is not fully described in the provided drug labels 2 3.

From the Research

Relationship Between Cancer and Pulmonary Embolism (PE)

• Cancer patients are at a higher risk of developing pulmonary embolism (PE), which is a marker of increased mortality in these patients 4.
• The incidence of PE in lung cancer patients is around 3.7%, and unsuspected pulmonary embolism (UPE) is also significant, ranging from 29.4% to 63% 5.
• The risk factors for PE in cancer patients can be classified into three categories: lung cancer-related, patient-related, and treatment-related factors 5.

Diagnosis and Treatment of Cancer-Associated PE

• Diagnosis of PE and risk stratification is possible with minor changes to existing risk scores, and thrombolytic therapy should be considered in appropriate patients 4.
• Prophylactic anticoagulant therapy may be beneficial in patients with stage IV non-small cell lung cancer (NSCLC) or limited small cell lung cancer (SCLC), with heparin being superior to warfarin for thrombotic prophylaxis 5.
• Direct oral anticoagulants (DOACs) are increasingly being used as an effective and safe alternative to low-molecular-weight heparin for the prevention and treatment of cancer-associated thrombosis 6, 7.

Clinical Characteristics and Management of Cancer-Associated PE

• PE is the second leading cause of death in cancer patients after the cancer itself, likely due to difficulties in diagnosing the disease 8.
• The risk of PE recurrence and case-fatality rate depends on the type of PE presentation, such as symptomatic PE, unsuspected PE, subsegmental PE, or catheter-related PE 8.
• Choosing the best therapeutic option is challenging and should consider the risk of both recurrence of thrombosis and occurrence of bleeding 8.