Antithrombin III Deficiency Workup

Author: James L Harper, MD; Chief Editor: Robert J Arceci, MD, PhD more...

Updated: Aug 1, 2011

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Laboratory Studies

Specific laboratory workup for suspected antithrombin III (ATIII) deficiency depends on the clinical setting.

Antithrombin assays

Antithrombin III activity should be measured first.

If low, then antithrombin antigen is measured to look for mutations consistent with type II disease.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT)

These studies allow evaluation of the presence of inappropriate activation of the coagulation system.

aPTT is a useful screen for antiphospholipid (AP) antibody syndrome.

aPTT-mixing study may distinguish between AP antibody syndrome and disseminated intravascular coagulation (DIC). Advanced DIC may present with a persistently prolonged aPTT if fibrin degradation products inhibit fibrin generation or acquired deficiencies of coagulation factors are severe.

Protein C (antigen and activity tests) and protein S (total and free tests)

Protein C or protein S deficiencies are both associated with venous thrombosis and are important exclusions in evaluating congenital deficiency of antithrombin III.

In the newborn, protein S activity must be measured (in addition to total) because, whereas total antigen levels are lower in neonates than in adults, protein S activity is usually normal because of the lack of expression of C4-binding protein in the neonate. (C4 acts to bind protein S in children and adults.)

These tests may also be important in the acquired state to determine the extent of a given patient's thrombotic risk.

Factor V Leiden testing

The most common congenital procoagulant disorder, factor V Leiden, occurs in about 5% of patients and needs to be documented when attempting to make the diagnosis of congenital antithrombin III deficiency. Knowing what this level is also helps to define a given patient's procoagulant risk.

Although factor V Leiden does not commonly produce thrombosis during childhood, it may contribute to thrombosis started by other etiologies (eg, central venous catheters).

Physicians should note that this is not a measurement of factor V activity but rather a determination of a specific mutation of factor V that leads to a decreased sensitivity to the inhibitory effects of protein C.

Homocysteine level

Increased levels of homocysteine are associated with an increased risk of thrombosis in adults, but this is rarely seen in children. In a child with elevated homocysteine levels, MTHFR gene analysis should be performed.

Anticardiolipin antibodies (both immunoglobulin G [IgG] and immunoglobulin M [IgM] class)

These should be measured by enzyme-linked immunoabsorbent assay (ELISA) or other physical means to rule out coexisting thrombotic risk from this source.

Echocardiography

This should be performed in all patients with antithrombin III deficiency, especially if they have evidence of arterial thrombus.

Arterial thrombosis due to antithrombin III deficiency is uncommon.

Venous clots may migrate to arterial circulation through a patent foramen ovale or other communicating congenital heart defect (eg, atrial septal defect, ventricular septal defect, truncus arteriosus).

Doppler ultrasonography

Doppler ultrasonography of the affected extremity with compression should be performed at diagnosis and then used in follow-up to determine resolution of an acute thrombus.

Ventilation-perfusion scanning

Pulmonary thrombosis can be imaged with ventilation-perfusion scan.

Thin-cut spiral CT scanning has also been used for this, but small lesions may be missed.

Procedures

Given the significant risk of venous thrombosis associated with central venous line (CVL) placement in children without signs of antithrombin III deficiency, those children known to have a congenital antithrombin III deficiency should have CVLs placed only if significant need outweighs increased potential risk of a clinically significant clot.

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Contributor Information and Disclosures

Author

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary R Jones, MD Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gary D Crouch, MD Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

David Pallares, MD Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

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