The Thrombophilic State in Cancer Patients

Abstract

Thrombosis and disseminated intravascular coagulation are common complications of cancer. Specific conditions associated with cancer such as stasis due to immobilization or blood flow obstruction, surgery, infections, endothelium damage due to chemotherapeutic agents and abnormalities of blood coagulation contribute to the hypercoagulable and thrombophilic state of cancer patients. This procoagulant state in cancer arises mostly from the capacity of tumor cells to express and release procoagulant activities (cancer procoagulant and tissue factor). Decreased levels of inhibitors of coagulation, impaired fibrinolysis, the presence of antiphospholipid antibodies and an acquired activated protein C resistance contribute to the hypercoagulable state. The activation of coagulation is also implicated in tumor proliferation through interactions of coagulation with inflammation and increased tissue factor pathway inhibitor. Laboratory diagnosis of the thrombophilic state include (1) elevation of clotting factors, fibrinogen/fibrin degradation products, hyperfibrinogenemia and thrombocytosis and (2) elevation of specific markers of activation of coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin complexes and D-dimers. However, none of the tests has any predictive value for the occurrence of thrombotic events in one individual patient. In patients with venous thromboembolism a noninvasive screening for occult cancer is able to detect a relatively high incidence of hidden cancer and the search for thrombophilia seems important in patients without known cancer.

Antiphospholipid Antibodies in Patients with Cancer

“…The relation between aPL antibody test positive at diagnosis of tumour disease and the high risk of developing thrombotic complications has been demonstrated (11)(12)(13)(14). In this study, we show for the first time the association between specific tumor markers and aPLs antibodies.…”

“…The OD units for each result were calculated on the basis of the standard curve. Samples with <10 GPL units, [10][11][12][13][14][15][16][17][18][19][20] Of the total patients, 19 were with low, moderate or high aCL-aPI antibody levels (Table I a aCL+; of the patients CA19.9 positive 37.5% was aCL+ and 62.5% aPI+; of the patients CEA-CA19.9 30% was aCL+ and 30% aPI+; of the patients CA125 positive 9% was aPI+; of the patients CEA-CA125 positive 100% was aPI+; of the patients CEA-CA15.3 25% was aCL+ and 25 aPI+ (Fig. 3).…”

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…It is well documented that activation of the blood coagulation cascade is a common feature of cancer and is associated with increased malignancy and poor outcomes. [33][34][35] Under non-pathological conditions, activation of the blood coagulation cascade is triggered in response to tissue injury or trauma and occurs through the activation of a suite of coagulation factors and complexes. 36 It is initiated by exposure of the subendothelial transmembrane glycoprotein, tissue factor (TF), to blood, where it forms a complex with circulating factor VIIa (TF:FVIIa).…”

A case of recurrent non-small-cell lung carcinoma and paraneoplastic Cushing's syndrome

“…Both active malignancy and Cushing's syndrome are associated with a hypercoagulable state because of an increase in plasma clotting factors like Factor VIII and von Willebrand factor complex, and to an impairment of fibrinolytic capacity [22,23]. This could explain why our patient suffered recurrent pulmonary embolisms despite adequate anticoagulant treatment.…”