抗リン脂質抗体陽性脳梗塞

Ischemic Stroke with Antiphospholipid Antibody

はじめに

　抗リン脂質抗体症候群は，動脈硬化を基盤としない後天的な血栓症の原因として第1位を占め，免疫学的な機序で起こる血栓症として重要である。抗リン脂質抗体症候群は一般に予後不良で血栓症の再発が多く，治療に抵抗性であり，多彩な合併症を呈する難治性の疾患である。抗リン脂質抗体の研究が精力的に行われ始めたのは1980年代の前半で，まだ30年弱の歴史しかないが，これらの研究は血栓症の機序の解明にとって多くの情報を与えてきた。本稿では抗リン脂質抗体症候群の臨床，病態，治療について，主に脳梗塞との関連で解説する。

Abstract

　Antiphospholipid syndrome is considered to be associated with a hypercoagulable state that leads to stroke and other ischemic events,and is currently diagnosed based on the modified Sapporo criteria that was proposed in 2006.　Antiphospholipid antibodies (aPL) comprise a heterogeneous group of autoantibodies.　Among them,the level of β2-glycoprotein I-dependent anticardiolipin antibody,lupus anticoagulant (LA),and IgG anticardiolipin antibody are commonly measured.　Recently,phosphatidylserine dependent anti-prothrombin antibody has been suggested to be closely related to LA.

　aPL is an independent risk factor for a first-ever ischemic stroke,especially in young female patients.　It is still debatable whether aPL is a marker for recurrent stroke risk.　The precipitating factors for the occurrence of stroke are β2-GPI-dependent aCL,aGPL,and aCL levels of greater than 40,and the simultaneous presence of LA.

　Several mechanisms are considered to be involved in the thrombotic process in patients with antiphospholipid antibodies.　Activation of protein C is impaired in patients with aPL.　β2-GPI has simultaneous procoagulant and anticoagulant effects.　Cardiac valvular involvement,which could be the cause of cardiogenic embolism,is prevalent in patients with aCL.　 In addition,the presence of aPL is associated with the development of atherosclerosis.　Recently,it has been proposed that endothelial cells,monocytes,and platelets were reported to be activated by β2-GPI: further,p38 mitogen-activated protein kinase has been reported to be phosphorylated.

　Several therapeutic options are available for the prevention of ischemic stroke in patients with aPL.　For cases of cryptogenic ischemic stroke and positive aPL antibodies,antiplatelet therapy is reasonable.　Oral anticoagulation with a target international normalized ratio (INR) of 2 to 3 is reasonable for patients with ischemic stroke who meet the criteria for antiphospholipid syndrome with venous and arterial occlusive disease in multiple organs.