Ovarian cancer and venous thromboembolic risk

Abstract

Objective.

To determine the incidence and the prognostic factors of objectively diagnosed deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with epithelial ovarian malignancy.

Methods.

We reviewed the records of all patients with epithelial ovarian cancer who were diagnosed, treated, and followed-up at our institution between 1990 and 2001. Data were collected regarding age, body mass index, previous DVT and PE, menopause status, FIGO stage, grade, histology, type of surgery, residual disease, first line chemotherapy, and relapse status.

Results.

Of the 253 cases, the overall incidence of symptomatic venous thromboembolic events (VTE) was 16.6% (42 patients): 1.6% (4) with PE and 15% (38) with DVT. 8 events (3.2%) were detected before tumor diagnosis, 6 (2.4%) in the postoperative period, 16 (6.4%) during first line chemotherapy and 12 (4.8%) throughout the follow-up period. Risk factors associated with occurrence of VTE were: at diagnosis, history of deep vein thrombosis (P = 0.001); during chemotherapy, older age (P = 0.017), larger body mass index (P = 0.019), FIGO stage 2c–4 (P = 0.004), no surgery (P = 0.003), and presence of residual tumor (P = 0.026). None of the considered risk factors were found to be predictors of VTE postoperatively. The multivariate regression analysis found that residual tumor, age, and body mass index were independent prognostic factors.

Conclusion.

The incidence of VTE throughout the entire history of ovarian malignancy is high. Prognostic factors could be used to establish prophylaxis protocols based on risk stratification.

Introduction

The association between cancer and venous thromboembolism (VTE) is well known. The pathogenic mechanism was described by Virchow with the triad of hypercoagulability, vessel wall injury, and stasis: a complex interaction between the tumor cell, the patient, and the hemostatic system.

Neoplastic cells can activate the clotting system directly, via thrombin generation, and indirectly by stimulating mononuclear cells to produce and express pro-coagulant substances [1].

Cancer cells can also injure endothelium by direct vascular invasion and by secretion of vascular permeability factors which account for extravascular accumulation of fibrinogen around tumor growth [2].

Extrinsic factors such as chemotherapy, and venous catheters are also responsible for direct injury of the vessel wall [3].

Venous stasis predisposes to venous thrombosis by preventing activated coagulation factors from being diluted and cleared by normal blood flow. Hypoxic damage to endothelial cells due to stasis may produce prothrombotic alterations. Venous stasis develops as a consequence of immobility in debilitated cancer patients, surgery, or as a result of venous obstruction due to extrinsic vascular compression in patients with bulky tumor masses [4].

Particularly, in patients with ovarian cancer, it has been shown that a hematocrit-independent hyperviscosity syndrome with elevated platelet count with the concurrence of increased coagulation activation, elevated plasma fibrinogen concentration, reduced red blood cells deformability, dehydration due to malignant ascites, and activation of the host inflammatory response, may alter the rheologic properties of blood and contribute to reduce blood flow. These facts may be associated with the spreading of disease and with a poor prognosis [5].

No study, so far, has provided evidence that any of the plasma markers of coagulation activation are indeed capable of identifying patients at risk of developing thrombotic complications. Because it is not possible to accurately predict who among patients with cancer will develop thrombosis, it appears reasonable to consider a strategy of routine anti-thromboprophylaxis in such patients. In order to verify this, it is essential to establish if the magnitude of VTE risk is sufficiently great, and if there are evaluable risk factors.

There are few studies about the incidence of VTE in ovarian cancer patients [5], [6], [7], [8] and most of them use non-objective diagnostic methods that may overestimate the clinical problem.

On these bases, we undertook the present study, in order to analyze the incidence and prognostic factors of deep vein thrombosis and/or pulmonary embolism in association with ovarian malignancy.