がん関連脳梗塞に対する抗血栓薬の考え方

抄録

The mechanism of cancer–related stroke is thought to be due to hypercoagulation caused by mucins produced by cancer cells, and tissue factors expressed on the surface of cancer cells, which can lead to thrombosis. However, the mechanisms of cancer–related stroke are diverse. In addition to direct tumor cell invasion, cardiogenic cerebral embolism due to nonbacterial thrombotic endocarditis (NBTE), and paradoxical cerebral embolism via a patent foramen ovale following deep vein thrombosis are not uncommon. Meanwhile, patients with atrial fibrillation and arteriosclerotic lesions are thought to be at even higher risk of ischemic stroke in the presence of cancer. Recently, we conducted a multicenter registry (CHALLENGE ESUS/CS) of patients undergoing transesophageal echocardiography for cryptogenic stroke. In sub–analysis of CHALLENGE ESUS/CS registry, compared with the non–cancer group, the active cancer group was related to multiple infarctions and high CRP levels, while the inactive cancer group showed significant associations with age, contralateral carotid artery stenosis, aortic arch plaque, and aortic valve calcification. Thus, cryptogenic stroke patients with a history of cancer still have high–risk of stroke.

Cancer–related stroke has a high recurrence rate and a poor prognosis. So far, little evidences have been available on the therapeutic strategy of cancer–related stroke. Sub–analysis of NAVIGATE ESUS and ARCADIA studies show no efficacy of DOACs for stroke prevention. Several retrospective studies indicated that heparin was effective for stroke prevention and reducing D–dimer levels. In the pilot study comparing low–molecular weighted heparin with aspirin, subcutaneous injection of low–molecular weighted heparin was shown as intolerable and cross–overed to aspirin. In the meta–analysis of such studies heparin and antiplatelet agents were shown as effective for stroke recurrence in cancer–related stroke.