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Presentation

History

The clinical presentation of antithrombin deficiency (AT deficiency) depends on whether patients develop venous or arterial thrombosis and on the extent of damage to the particular organ. Patients with lower extremity deep venous thrombosis (DVT) present in the usual manner, with unilateral leg edema; pain in the calf, thigh, or groin; and limitation of movement due to the presence of pain.

Pulmonary embolism (PE) may manifest as dyspnea, onset of pleuritic chest pain, and, rarely, hemoptysis. PE is underdiagnosed in many patients with DVT, because DVT, PE, or both may be not be clinically apparent.

The most common thrombotic manifestations include lower extremity venous thromboembolism (VTE), with recurrent VTE being common. Thrombosis involving the abdominal veins and/or other organs results in different manifestations and includes the onset of vague abdominal pain; postprandial exacerbation of abdominal pain, bloating, diarrhea, and/or hematochezia when mesenteric veins are involved^[55]; and, sometimes, ascites with right upper abdominal pain if portal or hepatic vein thrombosis is present.

Thrombosis of the retinal vessels causes visual defects, whereas cerebral venous sinus or arterial thrombosis results in central nervous system (CNS) manifestations that are related to the location of the thrombus. Other sites of thrombosis include the inferior vena cava and renal, axillary, brachial, or pelvic veins. Arterial thrombosis as the first manifestation of AT deficiency is less common.

In patients with thrombosis, it is important to look for other precipitating factors, such as the use of oral contraceptives or hormone replacement therapy, trauma,^[56]surgical procedures, pregnancy, and the postpartum state. Obtain a detailed family history, because an autosomal dominant pattern of inheritance may be evident. However, the lack of a positive family history does not exclude the presence of a thrombophilic mutation when a person is being evaluated for idiopathic or secondary thromboembolic disease.

Heparin causes an acquired reduction in AT levels. Several systemic diseases are also associated with reductions in AT.

Physical Examination

Physical findings depend upon the site of thrombosis. As indicated previously, VTE is much more common than arterial thrombotic disease.

Complications

Serious long-term morbidity can result from the following:

Venous and arterial thromboembolic events
Post-phlebitic syndrome due to extensive DVT
Recurrent VTE due to the discontinuation of oral anticoagulants
Sudden death due to the lack of prophylaxis in high-risk circumstances
Atypical site thrombosis such as Budd-Chiari syndrome
Bowel ischemia due to mesenteric vein thrombosis

Differential Diagnoses

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Media Gallery

Antithrombin (AT) neutralizes the enzyme (IIa) by forming a 1:1 stoichiometric complex (AT:IIa) between the arginine-serine sites of the 2 proteins. Binding of heparin to lysyl residues on AT results in a conformational change in AT, which makes it more available to bind thrombin (IIa), IXa, and Xa, thus markedly accelerating the rate of enzyme-inhibitor complex formation. AT also neutralizes XIa and XIIa.
Cell surface–directed hemostasis (image adapted from Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001). Initially, a small amount of thrombin is generated on the surface of the tissue factor–bearing (TF-bearing) cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation.
Antithrombin sites of action.

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Author

Drew H Barnes, MD Fellow Physician, Hospice and Palliative Medicine, The Ohio State University Wexner Medical Center

Drew H Barnes, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

David Aboulafia, MD Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Hematology, Infectious Diseases Society of America, Phi Beta Kappa

Disclosure: Nothing to disclose.

Bryan A Mitton, MD, PhD Clinical Instructor, Division of Pediatric Hematology-Oncology, Department of Pediatrics, Stanford University School of Medicine

Disclosure: Nothing to disclose.

Angela Steineck, MD, MS Assistant Professor of Pediatric Oncology, MACC Fund Center for Cancer and Blood Disorders - Children's Wisconsin, Medical College of Wisconsin

Angela Steineck, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Arun Rajan, MD Clinical Fellow, Medical Oncology Branch, National Cancer Institute/National Institutes of Health

Arun Rajan, MD is a member of the following medical societies: American Medical Association and American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Antithrombin Deficiency Clinical Presentation

History

Physical Examination

Complications

Complications

References

Tables

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