0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Reviews |

Hypercoagulable States

Ralph L. Nachman, MD; and Roy Silverstein, MD
[+] Article and Author Information

From the New York Hospital-Cornell Medical Center, New York, New York. Requests for Reprints: Ralph L. Nachman, MD, Cornell University Medical College, 1300 York Avenue, Room F-433, New York, NY 10021. Grant Support: By National Institutes of Health grants HL188281 (Specialized Center of Research in Thrombosis) and R01 (HL42540).


Copyright 2004 by the American College of Physicians


Ann Intern Med. 1993;119(8):819-827. doi:10.7326/0003-4819-119-8-199310150-00008
Text Size: A A A

Purpose: To describe the major pathophysiologic mechanisms underlying inherited and secondary hypercoagulable states and to evaluate the frequency, natural history, diagnosis, and management of the various clinical disorders.

Data Sources and Study Selection: Relevant clinical literature obtained from bibliographies in hematology textbooks and from computerized indexes was reviewed. A hypothesis was formed based on this literature review and on recent developments from a number of experimental studies.

Data Synthesis: Hypercoagulable states include various inherited as well as acquired clinical disorders characterized by an increased risk for thromboembolism. Primary hypercoagulable states include relatively rare inherited conditions that lead to disordered endothelial cell thromboregulation. These conditions include decreased thrombomodulin-dependent activation of activated protein C, impaired heparin binding of antithrombin III, or down-regulation of membrane-associated plasmin generation. The major, inherited, inhibitor disease states include antithrombin III deficiency, protein C deficiency, and protein S deficiency and should be considered in patients who have recurrent, familial, or juvenile deep-vein thrombosis or occlusion in an unusual location such as a mesenteric, brachial, or cerebral vessel. Secondary hypercoagulable states may be seen in many heterogeneous disorders. In many of these conditions, endothelial activation by cytokines leads to loss of normal vessel-wall anticoagulant surface functions with conversion to a proinflammatory thrombogenic phenotype. Important clinical syndromes associated with substantial thromboembolic events include the antiphospholipid syndrome, heparin-induced thrombopathy, the myeloproliferative syndromes, and cancer.

Conclusions: Physiologic thromboregulation occurs at the vessel-wall surface. Quantitative and qualitative deficiencies of normal, steady-state endothelial anticoagulant activities are associated with primary hypercoagulable states. Activated endothelial cell surfaces express a thrombogenic phenotype and contribute to secondary or acquired hypercoagulability.

Figures

Grahic Jump Location
Figure 1.
Anticoagulant inhibitory systems and the control of blood coagulation.

The orchestrated interactions of the four separate systems are shown: antithrombin III (AT III), activated protein C (PCa), tissue factor pathway inhibitor (TFPI), and plasmin. PL = the cellular phospholipid surface on which various macromolecular complexes assemble; II = prothrombin; and Fg =fibrinogen.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Endothelial cell thromboregulation.

Constitutive nonthrombogenic functions of the endothelium include thrombomodulin-bound thrombin generation of activated protein C, heparin antithrombin III, and plasmin generation. After an inflammatory stimulus, activated endothelium expresses tissue factor, cell adhesion molecules (CAM), plasminogen activator inhibitor (PAI-1), and platelet-activating factor (PAF). Plg = plasminogen.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Antithrombin. Methods Mol Biol 2013;992():355-64.
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)