Hypercoagulable states and cerebrovascular disease

Kathryn F Kirchoff-Torres MD (Dr. Kirchoff-Torres of Albert Einstein College of Medicine has no relevant financial relationships to disclose.)
Steven R Levine MD, editor. (

Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.

Originally released March 18, 1997; last updated April 25, 2019; expires April 25, 2022

This article includes discussion of hypercoagulable states and cerebrovascular disease, hypercoagulability, thrombophilia, and prothrombotic. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


In this update, the author discusses advancements in the epidemiology, diagnosis, treatment, and prognosis of patients with arterial ischemic stroke and cerebral venous thrombosis associated with genetic and acquired thrombophilia.

Key points


• Genetic and acquired hypercoagulable states, such as factor V Leiden deficiency and antiphospholipid syndrome, are associated with cerebrovascular events, including cerebral venous thrombosis and ischemic stroke.


• Understanding the pathophysiology of the hypercoagulable state is essential to understand the associated stroke syndromes and appropriate treatments.


• Study of the epidemiology, pathophysiology, and treatment of many recently described hypercoagulable states is an active and important area of research in neurology.


• Use of direct oral anticoagulants in patients with cerebral venous thrombosis or ischemic stroke due to antiphospholipid antibody syndrome and other thrombophilias is an area of active research.

Historical note and terminology

Rudolf Virchow proposed in 1862 that the pathophysiology of thrombosis involved a triad of interrelated factors: damage to blood vessel endothelium, stasis of blood flow, and disorders of blood coagulability.

Virchow's triad. The three factors contributing to thrombosis are vessel wall damage, stasis, and alterations in blood coagulability. Image: Virchow triad
Today, thrombophilia is broadly defined as both inherited and acquired conditions that predispose to venous or arterial thrombosis. The term "hypercoagulable state" is defined as a prothrombotic condition resulting from any specific disorders of blood coagulation. Although the clinical concept of hypercoagulability has been appreciated for decades, only since the 1980s has it been possible to identify an underlying disorder of coagulation in a subset of patients with thrombosis. These disorders may be hereditary or acquired. Activated protein C resistance due to factor V Leiden mutation, prothrombin 20210A gene mutation, protein C deficiency, protein S deficiency, and antithrombin III deficiency are the most frequently seen causes of a hereditary hypercoagulable state; antiphospholipid antibody syndrome is the most common acquired disorder.

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