Epidemiology
Patients with advanced metastatic disease of the brain, lung, stomach, pancreas, kidneys, uterus, and bladder have the highest 1-year VTE incidence rate, and are at a four to 13 times higher risk of developing VTE compared to those with localized disease.15 Approximately 15% of patients with a malignancy present with VTE at some point during the course of their illness16 compared to 2.5% of the general population.17 Furthermore, an increasing frequency of VTE among cancer patients has been observed over the years due to improved survival.18 The strongest predictor for recurrent VTE is a previous diagnosis of the condition.19 The prognosis of VTE depends on the aggressiveness of the underlying malignancy and the presence of other cancer-associated complications.20
In the postoperative setting, the risk of lower extremity DVT is about twice that of noncancer patients.21 While commonly noted, there is limited evidence to support the relationship between DVT location and cancer. It is reasonable, however, to propose that localized anatomical compression by the tumor of nearby veins causes stasis and subsequent DVT. Bilateral DVT of the lower extremities may be seen with pelvic malignancies, and DVT of the upper extremities is associated with central venous catheters, axillary lymphomas, mediastinal tumor masses, and intravenous (IV) chemotherapy. Idiopathic DVT is a significant risk factor for underlying malignancy, found in approximately 10% of cases.22 In a prospective study of patients with newly diagnosed DVT, Hettiarachchi, et al23 report routine clinical evaluations are sufficient to find underlying malignancies and that extensive screening is unwarranted.
Risk Assessment
The common risk factors of VTE in the general population are older age, female gender, race, prolonged immobilization, hospitalization, previous history of VTE, obesity, heart disease (ie, cardiomyopathy, atrial fibrillation), smoking, poor performance status, familial or acquired hypercoagulability (eg, pregnancy, hormone therapy, indwelling venous catheters). The cancer population, however, is unique and has other risk factors placing patients at risk for developing a VTE. Such risk factors can be grouped into four different categories: patient-related, cancer-related, treatment-related, and biochemical-related.
Patient-Related Risk Factors. These include age, obesity, smoking, decreased mobility, history of previous VTE, comorbidities, and the presence of prothrombotic mutations.
Cancer-Related Risk Factors. Risk factors for VTE depend on the site, stage, and histological type and time from diagnosis of the cancer. Brain tumors and stomach and pancreatic cancers are associated with a high risk of VTE.9,24 Timp, et al24 also studied a strong association between the 1-year relative mortality of a cancer type and its associated thrombogenic potential. In hematologic malignancies, patients with high-grade lymphoma and acute promyelocytic leukemia are at higher risk than other forms of lymphoma or leukemia.25
Treatment-Related Risk Factors. These include anticancer drugs (chemotherapy and hormonal therapy), radiation therapy, recent major surgery, and the presence of a central venous access device (CVAD).
Patients who received chemotherapy with thalidomide, lenalidomide, cisplatin, and platinum were found to be at high risk of developing VTE.9 Hormonal therapies including tamoxifen, raloxifene, oral contraceptives, and diethylstilbestrol phosphate (used in combination with doxorubicin) also increase the risk of VTE in cancer patients.26-28
The incidence of symptomatic catheter-associated thrombosis is shown to be as high as 28.3%.29 A recent meta-analysis of 11 studies showed that peripherally inserted central catheters are associated with a higher risk of DVT than are central venous catheters.30 Mural thrombus extending from the catheter into the lumen of a vessel and leading to partial or total occlusion with or without clinical symptoms is defined as CVAD-associated thrombosis.
Biochemical-Related Risk Factors. The patient’s hemoglobin level, leukocyte, and platelet counts are associated with an increased VTE risk. Patients with a hemoglobin level <10 g/dL and a leukocyte count >11 x 109/L had an almost 2-fold increased risk of developing a VTE in a study conducted by Khorana, et al.31 The Awareness of Neutropenia in Chemotherapy Group Registry Study reported that a platelet count ≥350 x 109/L prior to chemotherapy is associated with an increased risk of VTE.32