From the Guidelines
A low antithrombin III (ATIII) level is associated with an increased risk of thromboembolic complications, including deep vein thrombosis (DVT) and pulmonary embolism (PE) 1. The complications of low ATIII levels can be categorized into the following:
- Heparin resistance: defined as the need for a substantially higher-than-normal heparin dose to achieve a satisfactory safe level of anticoagulation or an inability to achieve satisfactory safe levels of anticoagulation 1
- Thrombosis: including DVT and PE, which can occur due to the decreased ability of ATIII to inactivate coagulation enzymes 1
- Catheter-related thrombosis: which can occur in patients with central venous catheters (CVC) and low ATIII levels 1 Patients with ATIII deficiency may require anticoagulation therapy with heparin or low molecular weight heparin to prevent thrombotic events 1. In severe cases, ATIII concentrate may be administered to rapidly correct the deficiency, with dosing adjusted to maintain an ATIII level above 80% of normal 1. Some key points to consider in the management of low ATIII levels include:
- ATIII supplementation: can be used to treat heparin resistance and prevent thrombotic events 1
- Heparin therapy: should be used with caution in patients with low ATIII levels, as they may be at increased risk of heparin resistance 1
- Catheter management: patients with CVC and low ATIII levels should be closely monitored for signs of catheter-related thrombosis, and anticoagulation therapy should be considered to prevent this complication 1
From the FDA Drug Label
Inactivation of thrombin by AT occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two, involving an interaction of the active serine of thrombin and an arginine reactive site on AT AT is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as plasmin. As the therapeutic antithrombotic effect of heparin is mediated by AT, heparin in vivo is ineffective in the absence or near absence of AT. None of the 13 subjects with hereditary AT deficiency and histories of thromboembolism treated prophylactically on 16 separate occasions with THROMBATE III for high thrombotic risk situations (11 surgical procedures, 5 pregnancies and/or deliveries) developed a thrombotic complication. Ten subjects with hereditary AT deficiency were treated with THROMBATE III as well as heparin (n=9) for major thrombotic or thromboembolic complications, including 4 subjects with thrombosis during the first trimester of pregnancy.
The complications of low Antithrombin III (ATIII) levels include:
- Thrombosis: Low ATIII levels can lead to an increased risk of thrombosis, as ATIII plays a crucial role in inactivating thrombin and other components of the coagulation cascade.
- Thromboembolism: Patients with hereditary AT deficiency are at risk of developing thromboembolic complications, including pulmonary embolism.
- Ineffective heparin therapy: Low ATIII levels can render heparin therapy ineffective, as heparin's antithrombotic effect is mediated by ATIII. 2
From the Research
Complications of Low Antithrombin III (ATIII) Levels
- Low ATIII levels are associated with an increased risk of thromboembolic complications, including deep vein thrombosis (DVT) and pulmonary embolism (PE) 3, 4, 5, 6, 7
- Patients with low ATIII levels are at higher risk of developing venous thromboembolism (VTE) compared to those with normal ATIII levels 4
- Low ATIII levels are also associated with prolonged length of stay and increased mortality in critically ill surgical patients 4
- In pregnant women with antithrombin deficiency, low ATIII levels increase the risk of thromboembolic events, and heparin resistance may occur 5
- Low ATIII levels can lead to heparin resistance, making it challenging to manage thromboembolic complications 5, 6
- Decreased ATIII activity is associated with an increased risk of thromboembolic complications, including DVT, disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS) 7
Specific Complications
- DVT: low ATIII levels increase the risk of DVT, particularly in patients with congenital ATIII deficiency 3, 4, 7
- Pulmonary embolism: low ATIII levels increase the risk of PE, particularly in patients with congenital ATIII deficiency 3, 4
- Disseminated intravascular coagulation (DIC): low ATIII levels increase the risk of DIC, particularly in critically ill patients 6, 7
- Adult respiratory distress syndrome (ARDS): low ATIII levels increase the risk of ARDS, particularly in critically ill patients 7