Question

Which of the following disorders is most commonly linked with ischemic stroke caused by a hypercoagulable (prothrombotic) state?

• A. Antiphospholipid syndrome (APS)
• B. Antithrombin III deficiency
• C. Factor V Leiden mutation
• D. Protein S deficiency

Hint:

To diagnose APS, a patient must meet at least one clinical criterion (vascular thrombosis or adverse pregnancy outcome) and at least one laboratory criterion (positive aPL antibodies on two or more occasions at least 12 weeks apart).
Paradoxically, while APS causes severe clotting in vivo, the presence of lupus anticoagulant typically causes a prolonged aPTT in vitro.

Answer 1

The Correct Option is A

Concept:
The clinical problem asks us to identify which of the listed hypercoagulable states is most strongly associated with arterial thrombosis, specifically manifesting as an ischemic stroke.
Explanation:
• Thrombophilias (prothrombotic states) can be inherited or acquired.

• A critical distinguishing factor among thrombophilias is their predilection for causing venous versus arterial thromboses.

• The inherited thrombophilias, which include Factor V Leiden mutation, Prothrombin gene mutation, Antithrombin III deficiency, Protein C deficiency, and Protein S deficiency, predominantly predispose patients to Venous Thromboembolism (VTE).

• Manifestations of these inherited conditions mostly include Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE).

• They rarely cause arterial thrombosis (like ischemic stroke or myocardial infarction) unless there is a paradoxical embolism through a patent foramen ovale (PFO).

• In contrast, Antiphospholipid Syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of antiphospholipid antibodies (Lupus anticoagulant, Anticardiolipin antibodies, Anti-beta-2-glycoprotein I antibodies).

• APS is uniquely characterized by its strong propensity to cause both venous AND arterial thrombotic events.

• Arterial thrombosis in APS most frequently involves the cerebral vasculature, making ischemic stroke or transient ischemic attacks (TIAs) one of the most common and devastating clinical presentations of the syndrome, especially in young patients.

• Therefore, among the choices provided, APS is the disorder most classically and commonly linked directly to ischemic strokes.
Final answer:
Antiphospholipid syndrome (APS) is the most likely cause of stroke among the given hypercoagulable conditions.