Anticoagulants for cancer-associated ischemic stroke

Abstract

Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism.

Keywords: Cancer-associated stroke; D-dimer; Hypercoagulability; Oral direct anticoagulants.

Figure 1

The pathophysiology of cancer-associated hypercoagulability and the pharmacological mechanism of anticoagulants. Cancer cell secretes several molecules, including tissue factors, cancer procoagulants, cytokines, and cancer mucin to accelerate coagulation cascade and platelet activation and then result in thromboembolism. Heparin promotes the activity of antithrombin III and then blocks the function of activated coagulation factors Xa and IIa. Low-molecular-weight-heparin blocks the function of Xa. Direct oral anticoagulants inhibit the function of coagulation factor Xa or IIa. Vitamin K antagonist, warfarin, block the synthesis of coagulation factors II, VII, IX, and X by inhibiting the function of carboxylase in hepatocytes (light gray line, activating; dot line inhibiting)