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Antithrombin III
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Dosage can be calculated from the following formula: Units required (International Units) = [desired concentration - baseline AT III concentration] x weight (kg)/1.4% (International Units/kg). In general, calculate initial loading dose to elevate the plasma AT III concentration to 120%, assuming an expected rise over the baseline AT III concentration of 1.4% (functional activity) per International Unit/kg of AT III administered. If the in vivo recovery differs from an anticipated rise of 1.4% for each International Units/kg administered, modify the formula accordingly. Plasma concentrations between 80% to 120% may be maintained with maintenance doses of 60% of the initial loading dose given approximately every 24 hours as needed. However, adjustments in the maintenance dose and/or interval between doses should be made based on actual plasma AT III concentrations achieved. In many cases, it is desirable to raise the AT III concentration to normal and maintain this concentration for 2 to 8 days, depending on the indication for treatment, type and extensiveness of surgery, the patient's medical condition and history, and the clinician's judgment.[30131]
Dosage can be calculated from the following formula: Units required (International Units) = [desired concentration - baseline AT III concentration] x weight (kg)/1.4% (International Units/kg). In general, calculate initial loading dose to elevate the plasma AT III concentration to 120%, assuming an expected rise over the baseline AT III concentration of 1.4% (functional activity) per International Unit/kg of AT III administered. If the in vivo recovery differs from an anticipated rise of 1.4% for each International Units/kg administered, modify the formula accordingly. Plasma concentrations between 80% to 120% may be maintained with maintenance doses of 60% of the initial loading dose given approximately every 24 hours as needed. However, adjustments in the maintenance dose and/or interval between doses should be made based on actual plasma AT III concentrations achieved. In many cases, it is desirable to raise the AT III concentration to normal and maintain this concentration for 2 to 8 days, depending on the indication for treatment, type and extensiveness of surgery, the patient's medical condition and history, and the clinician's judgment.[30131]
Dosage can be calculated from the following formula: Units required (International Units) = [desired concentration - baseline AT III concentration] x weight (kg)/1.4% (International Units/kg). In general, calculate initial loading dose to elevate the plasma AT III concentration to 120%, assuming an expected rise over the baseline AT III concentration of 1.4% (functional activity) per International Unit/kg of AT III administered. If the in vivo recovery differs from an anticipated rise of 1.4% for each International Units/kg administered, modify the formula accordingly. Plasma concentrations of 80% to 120% may be maintained with maintenance doses of 60% of the initial loading dose, given approximately every 24 hours as needed. However, adjustments in the maintenance dose and/or interval between doses should be made based on actual plasma AT III concentrations achieved. In many cases, it is desirable to raise the AT III concentration to normal and maintain this concentration for 2 to 8 days, depending on the indication for treatment, type and extensiveness of surgery, the patient's medical condition and history, and the clinician's judgment.[30131]
Dosage can be calculated from the following formula: Units required (International Units) = [desired concentration - baseline AT III concentration] x weight (kg)/1.4% (International Units/kg). In general, calculate initial loading dose to elevate the plasma AT III concentration to 120%, assuming an expected rise over the baseline AT III concentration of 1.4% (functional activity) per International Unit/kg of AT III administered. If the in vivo recovery differs from an anticipated rise of 1.4% for each International Units/kg administered, modify the formula accordingly. Plasma concentrations of 80% to 120% may be maintained with maintenance doses of 60% of the initial loading dose, given approximately every 24 hours as needed. However, adjustments in the maintenance dose and/or interval between doses should be made based on actual plasma AT III concentrations achieved. In many cases, it is desirable to raise the AT III concentration to normal and maintain this concentration for 2 to 8 days, depending on the indication for treatment, type and extensiveness of surgery, the patient's medical condition and history, and the clinician's judgment.[30131]
The baseline antithrombin III (AT III) concentration is usually expressed as a percentage of a reference plasma. To calculate the in vivo recovery, measure plasma AT III concentrations prior to the infusion and 20 minutes after the infusion (peak). Additionally, measure plasma concentrations of AT III at least every 12 hours and immediately before the next infusion to maintain plasma AT III concentrations more than 80% (range: 80% to 120%). Monitor plasma AT III concentrations more frequently if the half-life of AT III is shortened, such as after surgery, with hemorrhage or acute thrombosis, and during intravenous heparin administration. Measure antithrombin III concentrations before and 20 minutes after each infusion until predictable peak and trough concentrations have been achieved. Do not use immunoassays to measure AT III concentrations; immunoassays do not detect all hereditary AT deficiencies. Measure AT III concentrations by amidolytic assays using chromogenic substrates or by clotting assays.[30131]
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indication
Antithrombin, or Antithrombin III (AT III), is a thrombin inhibitor indicated for use in individuals with hereditary antithrombin deficiency for the treatment and prevention of thromboembolism and the prevention of perioperative and peripartum thromboembolism. AT III is a natural anticoagulant synthesized in the liver. It plays a major role in regulating blood clotting by inhibiting thrombin, plasmin, and several activated coagulation factors, such as IXa, Xa, XIa, and XIIa. AT III inactivates thrombin by forming a stable, covalent complex involving the active site of thrombin and a specific reactive site on the AT, helping to prevent excessive clot formation. AT III temporarily replaces the missing antithrombin in individuals with hereditary deficiency to restore anticoagulant function. The most commonly reported adverse reactions include dizziness, chest discomfort, and nausea. Antithrombin III was FDA-approved in 1991.[30131]
For storage information, see the specific product information within the How Supplied section.
Reconstitution
Intravenous Infusion
Human antithrombin III is derived from pooled human plasma. As with other products derived from or purified with human blood components, the remote possibility of contamination with bacterial or viral infection, including Creutzfeldt-Jakob disease (CJD), exists in patients receiving human antithrombin III. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents are present in the pooled product. Report all infections thought to have been transmitted by human antithrombin III to the manufacturer.[30131]
Hypersensitivity reactions, including anaphylactoid reactions, are possible with the administration of human antithrombin III (AT III). Early signs of hypersensitivity reactions which can progress to anaphylaxis include angioedema, chest tightness, hypotension, rash, upset stomach, vomiting, paresthesia, restlessness, wheezing, and difficulty breathing. If hypersensitivity occurs, discontinue AT III and administer appropriate treatment. Dizziness (12%), chest pain (unspecified) (3%), chest discomfort (9%), and dyspnea (3%) were reported during clinical trials in individuals receiving AT III.[30131]
Hematoma and wound secretion were reported in 3% (n = 1) of individuals receiving human antithrombin III during clinical trials and were described as severe.[30131]
Chills (3%), fever (3%), and pain/cramps (6%) were reported in individuals receiving antithrombin III during clinical trials.[30131]
Urticaria was reported in 3% of individuals receiving antithrombin III during clinical trials.[30131]
Nausea (9%), dysgeusia (6%), and intestinal dilatation (3%) were reported in individuals receiving antithrombin III during clinical trials.[30131]
During clinical trials, blurred vision was reported in 3% of individuals receiving antithrombin III.[30131]
The coadministration of certain medications may lead to harm and require avoidance or therapy modification; review all drug interactions prior to concomitant use of other medications.
This medication is contraindicated in patients with a history of hypersensitivity to it or any of its components.
Data are insufficient to advise a drug-associated risk of antithrombin III use during pregnancy. It is not known whether plasma-derived antithrombin III can cause fetal harm when administered to a pregnant person. Use antithrombin III during pregnancy only if clearly needed. During labor and obstetric delivery, suspend heparin or low molecular weight heparin and continue plasma-derived antithrombin III administration.[30131]
There are no data on the presence of antithrombin III in human milk, its effects on the breast-fed child, or its effects on milk production. Consider the benefits of breast-feeding, the patient's clinical need for antithrombin III, and any potential adverse effects on the breast-fed child from the medication or from the underlying maternal medical condition.[30131]
Antithrombin III (AT III) plays a major role in the regulation of hemostasis by inactivating thrombin; factors IXa, Xa, XIa, and XIIa; and plasmin. The activity of AT III results from the interaction between its active arginine site and the active serine residue on thrombin that forms a covalent, 1:1 complex. The neutralization rate of serine proteases by AT proceeds slowly in the absence of heparin but is greatly accelerated in the presence of heparin. As the therapeutic antithrombotic effect of heparin is mediated by AT, heparin in vivo is ineffective in the absence or near absence of AT. AT III temporarily replaces the missing antithrombin in individuals with hereditary deficiency to restore anticoagulant function.[30131]
In clinical situations that reduce AT III activity concentrations (e.g., disseminated intravascular coagulation (DIC), sepsis, trauma, surgery), heparin may become less effective. In most cases, the decrease in AT III activity associated with heparin administration (about 15%) is negligible. However, it has been shown that, in cases of DIC, heparin responsiveness depends on AT III activity and that normalization of AT III activity reduces the amount of heparin required for adequate anticoagulation. The ability of AT III to bind thrombin and Factor Xa is increased 300- to 1,000-fold when it is concurrently bound to heparin. Therefore, in patients with suspected heparin resistance, it may be desirable to raise the AT III activity 80% to 100% prior to and during heparin therapy. Although controlled trials are lacking, use of AT III concentrate in conjunction with extracorporeal circulation may improve the coagulation profile and reduce the amount of heparin necessary for anticoagulation.[25406]
Revision Date: 08/27/2025, 01:33:04 PMAntithrombin III (AT III) is administered intravenously.[30131]
The time to fall to 50% of the peak plasma concentration after initial administration is 22.3 hours and the biological half-life of antithrombin III is about 2.5 days based on immunologic assays and 3.8 days based on functional assays.[30131]
The half-life of antithrombin III has been reported to be shortened in patients after surgery, hemorrhage or acute thrombosis, and during heparin or low molecular weight heparin administration.[30131]
Data are insufficient to advise a drug-associated risk of antithrombin III use during pregnancy. It is not known whether plasma-derived antithrombin III can cause fetal harm when administered to a pregnant person. Use antithrombin III during pregnancy only if clearly needed. During labor and obstetric delivery, suspend heparin or low molecular weight heparin and continue plasma-derived antithrombin III administration.[30131]
There are no data on the presence of antithrombin III in human milk, its effects on the breast-fed child, or its effects on milk production. Consider the benefits of breast-feeding, the patient's clinical need for antithrombin III, and any potential adverse effects on the breast-fed child from the medication or from the underlying maternal medical condition.[30131]
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