Antithrombin Deficiency Clinical Presentation

  • Author: Arun Rajan, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

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 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 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[39] ; 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 antithrombin deficiency (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 (HRT), trauma,[40] surgical procedures, pregnancy, and the postpartum state.
    • Obtain a detailed family history, because an autosomal dominant pattern of inheritance may be evident. However, 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 antithrombin level. Several systemic diseases are also associated with reductions in antithrombin.
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Physical

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

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

Sara J Grethlein, MD  Senior Attending Physician, Cancer Treatment Center, Bassett Healthcare Network

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.

Specialty Editor Board

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, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and Southwest Oncology Group

Disclosure: No financial interests None None

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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Antithrombin (AT) sites of action.
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.
 
 
 
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