Antithrombin Deficiency Workup

Updated: Aug 22, 2019
  • Author: Bryan A Mitton, MD, PhD; Chief Editor: Perumal Thiagarajan, MD  more...
  • Print

Laboratory Studies

Important considerations during the laboratory workup of antithrombin deficiency (AT deficiency) include the following:

  • Appropriate timing of sample collection

  • Avoiding obtaining specimens during acute illnesses or in proximity to heparin administration; consider the impact of oral anticoagulants in normalizing the levels in some types of antithrombin deficiency

  • Considering the impact of oral anticoagulants in normalizing the levels in some types of antithrombin deficiency

  • Handling of the specimen in prompt fashion

  • Using appropriate methodology of functional and antigenic tests

  • Using biologic versus chromogenic substrate assays

The initial workup should include the following routine coagulation studies:

  • Prothrombin time (PT)

  • Activated partial thromboplastin time (aPTT)

  • Fibrinogen level

Special laboratory tests

Two types of biologic assays measure antithrombin activity. The first is the heparin cofactor assay of antithrombin activity, which measures the ability of antithrombin to bind heparin and neutralize thrombin or factor Xa.

The second test measures the ability of antithrombin to progressively neutralize thrombin in the absence of heparin. HCII also has heparin cofactor activity, but it is able to neutralize thrombin only in the presence of a large amount of heparin. Thus, the use of low concentrations of heparin and of factor Xa (rather than thrombin) in the assay system excludes the contribution of heparin cofactor II (HCII) in the heparin cofactor assay of antithrombin activity.

The antigen assay and presence of abnormal molecules by electrophoretic mobility require further immunologic assessment or DNA sequencing to characterize the specific defect present. Assessment of the specific genetic defect allows for early and easy identification of carriers and of risk assessment, as well as provision of genetic counseling and anticipatory guidance.

While the optimal, cost-effective workup for an inherited coagulopathy varies from center to center, currently available tests include the following:

  • Protein C activity

  • Free protein S antigen and activity

  • Thrombomodulin and MTHFR gene mutations

  • Fasting homocysteine levels

  • Plasminogen activity

  • Plasminogen activator inhibitor type 1 (PAI-1)

  • Tissue factor pathway inhibitor (TFPI) activity


Imaging Studies

Objective documentation of all thromboembolic disease is essential. The various imaging techniques available include compression and color ultrasonography, venography, angiography, computed tomography (CT) scanning, and magnetic resonance imaging (MRI). The specific imaging modality depends on the location of the suspected thrombus.


Other Tests

Decisions about proceeding with additional tests, including genetic tests, are based on the patient's history and their current medications.

Gene-based tests require that the potential implications, such as the inherited nature of the defect and insurance issues, be discussed with the patient before blood is drawn. The need for genetic counseling should be discussed after test results become available.