antithrombin III

Action and Spectrum

Actions and spectrum: 

antithrombin III (AT III) is a naturally occurring protein that acts as an anticoagulant in the body. It belongs to the serine protease inhibitor (serpin) family and functions by irreversibly binding and inactivating several coagulation factors, especially thrombin and Factor Xa. Thrombin and Factor Xa are crucial enzymes in the coagulation cascade, and their inhibition by antithrombin III leads to the prevention of the formation of blood clots. 

antithrombin III has a broad spectrum of action, inhibiting coagulation factors in both the intrinsic and extrinsic pathways, as well as the common pathway of the coagulation cascade. Additionally, it inhibits thrombin generation and fibrinolysis, the process by which clots are broken down. antithrombin III is also involved in maintaining vascular integrity and has anti-inflammatory properties, making it a potential therapeutic target for a range of conditions beyond anticoagulation. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Chest pain (≤2%) 

Hematoma (≤2%) 

Hematuria (≤2%) 

Abnormalities of Liver enzyme (≤2%) 

Hemarthrosis (≤2%) 

Hemorrhage (≥5%) 

Infusion site reaction (≥5%) 

Dizziness (7%)  

<1% 

Chills 

Dysgeusia 

Hives 

Foul taste 

Lightheadedness 

Bowel fullness 

Cramps 

Dyspnea 

Fever 

Film over eye 

Nausea 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

antithrombin III is contraindicated in individuals who have had a previous allergic or hypersensitivity reaction to the medication. It should also not be used in patients with a known hypersensitivity to heparin or heparin-induced thrombocytopenia (HIT). Additionally, antithrombin III should be used with caution in patients with a history of bleeding disorders, recent surgery, or those at risk of bleeding.  

Caution: 

• Allergic reactions: Patients with a known allergy to antithrombin III or other blood products should not receive antithrombin III. 
• Thrombosis: antithrombin III is used to treat thrombotic conditions, but it can also increase the risk of thrombosis (blood clots) if not used appropriately. Therefore, it should be used under caution in patients with a history of thrombosis or those at high risk for thrombosis. 
• Bleeding: antithrombin III can increase the risk of bleeding, especially when given at high doses. Patients with a bleeding disorder or those taking anticoagulant medication should be monitored closely. 
• Renal failure: antithrombin III is cleared from the body by the kidneys. Patients with renal failure may have impaired clearance and require a lower dose. 
• Hepatic failure: antithrombin III is produced in the liver, and patients with hepatic failure may have lower levels of antithrombin III. They may require a higher dose to achieve therapeutic levels. 
• Pregnancy and lactation: antithrombin III should be used with caution during pregnancy and lactation. The potential benefits of treatment should be weighed against the potential risks to the fetus or infant.

Comorbidities: 

antithrombin III is typically used as a treatment for various thromboembolic disorders, such as pulmonary embolism, deep vein thrombosis, and disseminated intravascular coagulation (DIC). Therefore, patients with these conditions would be the ones receiving antithrombin III therapy. 

As for comorbidities, patients with bleeding disorders, such as hemophilia, may need to be monitored more closely during antithrombin III therapy to avoid bleeding complications. Additionally, patients with liver disease or dysfunction may not be able to produce sufficient antithrombin III, so they may require higher doses of the medication. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: It is not known whether antithrombin III can pass into breast milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

antithrombin III (ATIII) is a natural anticoagulant protein that is synthesized by liver and circulates in the bloodstream. antithrombin III belongs to the serine protease inhibitor (serpin) family of proteins and functions as an inhibitor of thrombin and other coagulation proteases such as factors IXa, Xa, XIa, and XIIa. 

antithrombin III works by binding to the active site of these proteases, thereby inducing a conformational change in the protease that inactivates its activity. This process is augmented by the presence of heparin or other glycosaminoglycans, which bind to both antithrombin III and the protease and accelerate the inactivation process. 

antithrombin III also has anti-inflammatory properties and can inhibit the activity of several pro-inflammatory proteases, including kallikrein, plasmin, and elastase. Additionally, antithrombin III has been shown to have a role in regulating vascular tone and maintaining endothelial function.  

Pharmacodynamics: 

antithrombin III (ATIII) is a naturally occurring anticoagulant that inhibits the activity of several coagulation factors, particularly thrombin (Factor IIa) and Factor Xa. antithrombin III binds to these coagulation factors and neutralizes their activity, preventing the formation of fibrin clots. It also has anti-inflammatory effects and can inhibit the activation of certain cytokines and the complement system. 

antithrombin III works in conjunction with heparin, a commonly used anticoagulant. Heparin increases the activity of antithrombin III, allowing it to more effectively neutralize thrombin and other coagulation factors. 

The pharmacodynamics of antithrombin III can be monitored by measuring its plasma concentration and activity levels.  

Pharmacokinetics: 

Absorption 

antithrombin III is typically administered intravenously, which means it is injected directly into the bloodstream. As a result, absorption is not a relevant issue for antithrombin III. 

Distribution 

Once antithrombin III enters the bloodstream, it is distributed throughout the body. antithrombin III has a relatively short half-life of about 2-3 days, which means it is cleared from the body relatively quickly. 

Metabolism 

antithrombin III is metabolized in the liver, where it is broken down into smaller fragments and eliminated from the body. 

Elimination and excretion 

The majority of antithrombin III is eliminated from the body through the kidneys, although a small amount may also be eliminated through the liver. 

Adminstartion

Administration: 

antithrombin III (ATIII) is a medication that is typically administered by intravenous injection. It is used as an anticoagulant to prevent blood clots in a variety of medical conditions, such as pulmonary embolism, deep vein thrombosis, and disseminated intravascular coagulation. 

The specific dosing and administration of antithrombin III will depend on the patient’s medical condition, age, weight, and other individual factors. In general, the recommended dosage of antithrombin III is based on the patient’s body weight, with higher doses given to patients who are heavier. 

antithrombin III may be administered as a one-time dose or as a series of doses over a period. The specific dosing and duration of treatment will depend on the patient’s medical condition and response to treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: antithrombin III 

Pronounced: [ an-tee-THROM-bin]  

Why do we use antithrombin III? 

• Hereditary antithrombin III deficiency: People with this condition have a genetic defect which causes them to produce less antithrombin III than normal, which increases their risk of developing blood clots. 
• Prevention of deep vein thrombosis (DVT): antithrombin III is used in combination with heparin for the prevention of DVT in patients undergoing surgery or those who are immobilized for an extended period. 
• Treatment of disseminated intravascular coagulation (DIC): DIC is a serious condition that occurs when there is excessive activation of the clotting system in response to various underlying conditions, including severe infections, trauma, cancer, and other diseases.  
• Treatment of acute myocardial infarction: antithrombin III has been shown to have potential benefits in the treatment of acute myocardial infarction (heart attack) by reducing the risk of reinfarction and recurrent ischemic events. 
• Treatment of sepsis-induced coagulopathy: antithrombin III may be used in the treatment of sepsis-induced coagulopathy to reduce the risk of organ failure and death.