Antithrombin III Deficiency Clinical Presentation

Updated: Feb 10, 2018
  • Author: James L Harper, MD; Chief Editor: Hassan M Yaish, MD  more...
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Presentation

History

Antithrombin III (ATIII) deficiency is most commonly associated with venous thrombosis. Guidelines for VTE have been established. [13] History should focus on current symptoms, defining the patient's personal medical history in terms of thrombosis and thrombotic symptoms, as well as determining if other procoagulant risk factors are present. Often, children with antithrombin III deficiency present with unusual clot locations (eg, mesenteric veins, splenic veins).

Other risk factors include the following:

  • Presence of a central line currently or in the past (This is an especially common risk factor for thrombosis in infants and small children, in whom the lumen of the vessel is small, and blood flow around the catheter is no longer laminar)

  • Medications known to be procoagulant or medications that nonspecifically impair protein synthesis (eg, L-asparaginase) [14]

  • Other diseases associated with procoagulant states (systemic lupus erythematosus [SLE], nephrotic syndrome, bone marrow transplantation, trauma)

  • Presence of a second pro-coagulant disorder (acquired or inherited)

  • Non-O ABO phenotype (This has been associated with increased thrombotic risk in other procoagulant conditions [prothrombin G20210A]; although little is known of the impact of ABO phenotype on more severe procoagulant conditions like antithrombin deficiency, the ABO phenotype should be documented.)

Personal history of thrombosis is particularly important in terms of treatment. Patients with congenital antithrombin III deficiency who have had one unprovoked thrombotic event (particularly in the mesenteric or splanchnic systems) are much more likely to have recurrent clots. These patients are usually treated with indefinite anticoagulant therapy; thus, careful review of this area is wise.

Family history may be helpful. However, due to a late onset of venous thrombosis and a relatively recent development of the ability to accurately screen for specific defects, many patients have family histories that are negative for the condition, even in affected kindreds. Family history topics should include venous thrombosis of the splanchnic system, thrombosis in any vessel without evident cause of local etiology, and recurrent miscarriages.

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Physical

See the list below:

  • No physical stigmata are associated with congenital antithrombin III deficiency.

  • Homozygote-deficient newborns may have purpura fulminans-type presentation with embolic lesions in the skin. Heterozygote newborns are typically normal in appearance and do not commonly develop purpura fulminans unless coexisting risk factors are present.

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Causes

See the list below:

  • Deficiency may be due to several different genetic defects associated with differing degrees of enzyme production, enzymatic activity, and chemical stability (see Pathophysiology).

  • Certain abnormal alleles have been associated with specific clinical features (Wibble and Wobble, mutations in the "shutter" region of the enzyme), and others have yet to be studied.

  • Acquired antithrombin III deficiency is usually due to abnormal activation of a coagulation pathway or synthetic defect, often from medication (eg, L-asparaginase) or liver disease.

  • Antithrombin III may be lost in third spaces when it redistributes into edematous tissues. Antithrombin III may also be lost as part of increased protein losses seen in nephrotic syndrome, and this should be suspected if clotting occurs.

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